MX2008006849A - Diarylether derivatives as antitumor agents - Google Patents

Abstract

An object of the present invention is to provide a medicinal drug much improved in anti tumor activity and excellent in safety. According to the present invention, there is provided a medicinal drug containing a compound represented by the following general formula (1) or a salt thereof as an active ingredient:[Formula 1]wherein X1represents a nitrogen atom or a group -CH=, R1represents a group -Z-R6, in which Z represents a group -CO-, a group -CH(OH)- or the like, R6represents a 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms, R2represents a hydrogen atom or a halogen atom, Y represents a group -O-, a group -CO-, a group -CH(OH)- or a lower alkylene group, and A represents [Formula 2]wherein R3represents a hydrogen atom, a lower alkoxy group or the like, p represents 1 or 2, R4represents an imidazolyl lower alkyl group or the like.

Description

DERIVATIVES OF DIARILIC ETHER AS ANTINEOPLASIC AGENTS FIELD OF THE INVENTION The present invention relates to a medicinal drug.

BACKGROUND OF THE INVENTION Since the clinical use of nitrogen mustard as an anticancer agent for the first time in the world in the 40s, numerous anticancer drugs have been developed. In reality, for example, antimetabolites such as 5-fluorouracil, antineoplastic antibiotics such as adriamycin, platinum complexes such as cisplatin, and carcinostatic plant-derived such as vindesine have been subjected to clinical use. However, most of these carcinostats have significant side effects such as digestive disorders, myelosuppression and alopecia since they are also cytotoxic for normal cells. Due to the side effects, its range of application is limited. In addition, the therapeutic effects themselves are partial and short, in most cases. The development of new carcinostatics instead of these has been carried out; however, satisfactory results have not yet been obtained. The patent documents REF .: 192661 1 and 2 describe that certain types of compounds have inhibitory actions of fiber formation. However, it is unknown whether the compounds have antineoplastic actions. [Patent Document 1] WO / 2006/014012 [Patent Document 2] JP-A-2004-35475 BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is therefore to provide an excellent medicinal drug such as a therapeutic drug for a tumor, particularly, a therapeutic drug for a malignant tumor. The present inventors carried out intensive studies with the intention of achieving the aforementioned objective. As a result, they found that a compound represented by the general formula (1) below and a salt thereof have an excellent antineoplastic effect. The present invention has been achieved based on the discovery. More specifically, the present invention provides medicinal drugs shown in items 1 to 58. Element 1: An antineoplastic agent comprising a compound represented by the general formula (1) below, or a salt thereof as an active ingredient: Formula 1] Where Xi represents a nitrogen atom or a group -CH =, Ri represents a group -Z-R6, Z represents a group -N (R8) -B-, a group -BN (R8) -, a group - B0-O-, a group [Formula 2] 10 -NHCO- SL a group -CO-, a group -CH (OH) -, a group -N (R9a) -CO-N- (R9b) -, a group -N = CH-, a group -N (R10a) -S02- (B22a) e-, a lower alkenylene group, a -NHCO-B? - group, a -NHCO-B2- () u- group, a -Bo-0-B? 9a- group, a group [Formula 3 ] , a group [Formula 4] / \ -N N- (B2? A) c- , a group -S02-N (R10b) -, a group -S-, an alkynylene group lower, a lower alkylene group, a group -N (R8d) - or a group -CO-NH-B18a-, R8 represents a hydrogen atom, a lower alkyl group which may have a lower alkoxy group as a substituent, a group lower alkanoyl, a lower alkylsulfonyl group or a lower alkyl phenyl group, B represents a -CO- group or a lower alkylene group, Bo represents a lower alkylene group, Bi represents a lower alkenylene group which may have a phenyl group as a substituent, B2 represents a lower alkylene group which can be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group, R9a represents a hydrogen atom or a lower alkyl group, Rg represents a hydrogen atom or an alkyl group lower, Rioa represents a hydrogen atom or a lower alkyl group, B22a represents a lower alkylene group or a lower alkenylene group, e represents 0 or 1, Bisa represents a lower alkylene group, B? ga represents a lower alkylene group, B2oa represents a lower alkylene group, B2? A represents a lower alkylene group, k represents 2 or 3, c represents 0 or 1, d 'represents 0 or 1, Riob represents a hydrogen atom or a lower alkyl group, R8d represents a hydrogen atom or a group lower alkyl, W represents an oxygen atom, a group -NH-, or a sulfur atom, u represents 0 or 1, R6 represents a 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (which may have 1 to 3 substituents, which are selected from the group consisting of an oxo group); a lower alkoxy group which may have a halogen atom as a substituent; a lower alkyl group which may have a halogen atom as a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group which may be substituted by a lower alkyl group which may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantyl group, a naphthyl group (which may have 1 to 3 groups selected of the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), a alkyl group which may have a lower alkoxy group as a substituent, a cycloalkyl group which may be substituted by a group selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may be have a halogen atom as a substituent, in the cycloalkyl ring, a lower alkenyl group which may have a halogen atom corao a substitute present, a lower alkanoyl group, a benzoyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkyl group which may have a halogen atom and a halogen atom, as a substituent, on the phenyl ring), a lower alkyl group substituted with halogen atom, cycloalkyl lower alkyl group or a group Formula 5] R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group which may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group , a cyano group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a heterocyclic group of 5 or 6 saturated or unsaturated members having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (which may have an oxygen group) or in the heterocyclic ring), m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R7s can be identical or different) and R2 represents a hydrogen atom, an atom of halogen, or a lower alkyl group, Y represents a group -0-, a group -N (R5) -, a group -CO-, a group -CH (OH) -, a lower alkylene group, a -S group ( 0) n-, or a group -C (= N-0H) -, R5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group, n represents 0, 1 or 2, A represents a group [Formula 6] , or a group [Formula 7] p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a - C0NR ?: LR12, or a cyano group, wherein R11 and R12 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R11 and R12, together with the nitrogen atom to which they are attached, may joining one to the other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, R4 represents an imidazolyl lower alkyl group, a group 1, 2, 4 -triazolyl lower alkyl, a 1,2,3-triazolyl lower alkyl group, a 1, 2, 5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent in the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1, 2, 4 ring Oxadiazole, a thiazolidinyl alkyl group in ferior which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 8] a group [Formula 9] or a group? -N (R14) R15, R13 represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkanoyl group which may have a halogen atom as a substituent, a group lower alkoxycarbonyl, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group, a lower alkanoyl group substituted with morpholino, a piperazinyl carbonyl lower alkyl group which may be substituted, on the piperazine ring, by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl piperazinyl group which may be substituted, in the piperazine ring, by a phenyl lower alkyl group which may have an alkylenedioxy group erior as a substituent on the phenyl ring, a lower alkyl group substituted with raorfolinocarbonyl, or a lower alkanoyl imidazolyl group, R13a represents a hydrogen atom or a hydroxyl group, T represents a lower alkylene group, a group - N (R17) -B3-CO-, a group -B19-N (R18) -CO-, a group -B4-CO -, a group -Q-B5-CO-, a group -B6-N (R19) -B -CO-, a group -CO-B8-, a group -CH (OH) -B9-, a group -CO -B? 0-CO-, a group -CH (OH) -Bn-CO-, a group -CO-, a group -S02-, or a group -B23a-CO-CO-, wherein R17 represents an atom of hydrogen, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkenyl group, an amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group, B3 represents a lower alkylene group, B19 represents a lower alkylene group, Rie represents a hydrogen atom or a lower alkyl group, B4 represents a lower alkenylene group or an lower alkylene group ior which may have a hydroxyl group as a substituent, Q represents an oxygen atom or a group -S (0) n- (where n is equal to that described above), B5 represents a lower alkylene group, B6 represents an alkylene group lower, R19 represents a hydrogen atom or a lower alkanoyl group, B7 represents a lower alkylene group, B8 represents a lower alkylene group, B9 represents a lower alkylene group, Bio represents a lower alkylene group, Bu represents a lower alkylene group, B23a represents a lower alkylene group, lower alkylene group, 1 represents 0 or 1, R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents (2) an alkyl group substituted with a hydroxyl group, (3) a cycloalkyl group which may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; a lower alkoxy amino group which may have a lower alkyl group as a substituent; a lower alkyl group substituted with a hydroxyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group that may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group having a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkyl group substituted with lower alkoxycarbonyl , (11) a lower alkyl group substituted with carboxy, (12) an amino group which may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group which may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent (s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkyl group which may be substituted, on the piperazine ring, by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a group pyridyl lower alkyl, (17) a lower alkyl group substituted with an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkyl lower alkoxy group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a lower alkyl group substituted with 1,2,3,4-tetrahydroisoquinolylcarbonyl, (22) a piperidinylcarbonyl group which may have a group selected from the group consists of a lower alkoxycarbonyl group, a lower alkyl phenyl group, and a lower alkyl furyl group as a substituent on the piperidine ring, (23) an alkyl thiazolidinyl group lower, which may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group which may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl group lower alkyl, a lower alkyl group, a benzoyl group, and a lower alkyl furyl group, (25) a lower alkyl carbonyl group substituted by a group [Formula 10 , (26) a lower alkyl carbonyl group substituted by a group [Formula 11] (27) a group -CO-B20-N (R36) R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a lower alkyl morpholino group, (28a) a lower alkenyl phenyl group, (29a) an anilinocarbonyl alkyl group lower, which may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group which may have, as a substituent on the piperazine ring, a group selected from the group consists of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group which may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group which may have a lower alkyl group as a substituent on the carbazole ring, (35a) a group amidino which may have a lower alkyl group as a substituent, (36a) an oxalyl group substituted with piperazinyl which may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (which may have 1 to 3 groups selected from the group which consists of a lower alkylenedioxy group and a lower alkoxy group as a substituent (s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent (s) on the piperazine ring, or (37a) a substituted lower alkyl group with cyano, R34 represents an oxo group or a phenyl group, d represents an integer from 0 to 3, B2o represents a lower alkylene group, R36 and R37, together with the nitrogen atom to which they are attached, can bind to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups they may have a lower alkylenedioxy group on the phenyl ring, they may be present as a substituent (s), R14 and R15, together with the nitrogen atom to which they are attached, may be attached to each other, directly or via a hydrogen atom. nitrogen, oxygen atom, or sulfur atom to form a heterocyclic ring of 5 to 10 merobes saturated or unsaturated; or a group [Formula 12] wherein, in the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a lower alkyl group substituted with phenyl, having 1 to 2 phenyl groups which can be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group which can have a lower alkanoyl group as a substituent, an alkoxycarbonyl group lower, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, and which may have a pyridyl group in the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group which may have, as a substituent (s) in the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, (31) an alkynyl pyrrolyl group lower uilo which may have 1 to 3 lower alkyl groups as a substituent (s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a lower alkyl furyl group, (35) ) a benzoyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group which can have a lower alkylsulfonyl group as a substituent, a halogen atom, a group lower alkoxy, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a piperazinyl group, (38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkyl group which may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group [Formula 13] R = N-N = (Rb (where Ra and Rb each represent an alkyl group lower), (41) a lower alkyl group which may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a lower alkanoyl group which may have a halogen atom as a substituent , (43) a phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have an atom of halogen as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group which may have a halogen atom or as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which can have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (49) a group - (B? 2CO) tN (R20) R21, (50) a group - (CO) or B? 3-N (R22) R23, (51) a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which can be to be substituted, in the ring of 1, 2, 3, 4-tetrahydronaphthalene, by 1 to 5 lower alkyl groups as a substituent (s), (52) a cycloalkyl group which may have a hydroxyl group as a substituent, (53) a piperidinyl group which can be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent (s) , (54) a lower alkyl quinolyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group which may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent in the tetrazole ring, (56) a thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring, (57) a benzoyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent (s) on the phenyl ring, (58) a lower alkyl piperidinyl group which may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group which may have 1 to 3 phenyl groups as a substituent (s) on the imidazole ring, (60) a benzimidazolyl group which may have 1 to 3 lower alkyl groups, or a substituent (s) on the benzimidazole ring, (61) a lower alkoxy pyridyl group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group which may have an oxo group as a substituent in the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a lower alkoxy carboxy group, (75) a lower alkanoyl phenoxy group, (76) a 1,2,3,4-tetrahydroquinolylcarbonyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) a imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group - (0-B15) s-CO-N (R26) R27, (85) a group -N (R28) -CO-B? 6-N (R29) R30, (86) a group -N (R31) ) -BX7-CO-N (R32) R33, (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group that can be have an oxo group as a substituent on the tetrahydroquinoline ring, B12 represents a lower alkylene group, t represents 0 or 1, R20 and R21 may be identical or different and each represents a hydrogen atom; an amino group which may have a lower alkoxycarbonyl group as a substituent; a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group; a group phenyl which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group which may have 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent on the pyrrolidine ring; a lower alkyl group substituted with amino which may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as a substituent (s) on the 1, 2, 3, 4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a lower alkyl pyridyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent (s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group; a phenoxy lower alkyl group which may have 1 to 3 selected groups of the group consisting of a lower alkyl group and a nitro group as a substituent (s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group which may have a halogen atom as a substituent; a lower alkanoyl imidazolyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a lower alkyl carboxy group, or a cycloalkyl group; and R20 and R21, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 7. members (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group which may have 1 to 3 groups selected from the group consisting of one atom of halogen and a lower alkyl group which may have a halogen atom as a substituent (s) on the phenyl ring, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), or represents 0 or 1, B13 represents a lower alkylene group, R22 and R23 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a benzoyl group which may have 1 to 3 groups lower alkoxy such as a titanium ring (s) on the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group, a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R 22 and R23, together with the nitrogen atom to which they are attached, can be bound to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring (in where, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), B15 represents a lower alkylene group, s represents 0 or 1, R26 and R27 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or a lower alkyl imidazolyl group, and R26 and R27, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a heterocyclic ring saturated with to 7 mierabros, (wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups which may have a lower alkylenedioxy group as a substituent may be present on the phenyl ring, as a substituent (s)), R28 represents a hydrogen atom or a lower alkyl group, Biß represents a lower alkylene group, R29 and R30, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, a oxygen, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a group phenyl, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, R 31 represents a hydrogen atom or a lower alkyl group, B 1 represents an alkyl group lower ileum, R32 and R33, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic group of 5. to 7 mierabros, (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a lower alkyl group; substituent on the phenyl ring), provided that the aforementioned compound or a salt thereof satisfies the following requirements (i) to (v): (i) when Xi represents a group -CH =, then R3 represents a hydrogen atom; (ii) when Xi represents a group -CH =, 1 represents 1, T represents -CO-, and R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents the group (24); (iii) when Xx represents a group -CH =, 1 represents 1, and T represents -N (R17) -B3-CO-, R14 and R15, together with the nitrogen atom to which they are attached, can bind to each other , directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated or unsaturated 5- to 10-membered heterocyclic ring, wherein, in the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent (s); (iv) when Xi represents a nitrogen atom, and 1 represents 0, or when Xi represents a nitrogen atom, 1 represents 1, and T represents -CO- or -S02, R15 is not a group (5), (7) ), (19), or (20); and (v) when R6 represents a cycloalkyl group which may have on the cycloalkyl ring, a substituent selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have one atom of halogen as a substituent, R4 represents a group - (T) iN (R14) R15 (wherein T and 1 are the same as those described above, and R14 and R15, together with the nitrogen atom to which they are attached, can bind one to the other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 10 members, or R14 and R15 form a group [Formula 14] Element 2: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-1) to (1-7) below or a salt thereof as an active ingredient: [Formula 15] TO (1-1) (1-2) (1-3) (1-4) (1-5) (1-6) (1-7) wherein Y3 represents a lower alkylene group. Element 3: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-8) to (1-14) below or a salt thereof as an ingredient active: [Formula 16] (1-8) (1-9) (1-10) (1-11) (1-12) (1-13) (1-14) wherein Y represents a lower alkylene group. Element 4: The antineoplastic agent according to item 1, comprising a compound selected from the group consisting of the co-fractions represented by the general formulas (1-15) to (1-21) below or a salt thereof as an ingredient active: [Formula 17] (1-15) (1-16) (1-17) (1-18) (1-19) (1-20) (1-21) wherein Y3 represents a lower alkylene group. Element 5: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-22) to (1-28) below or a salt thereof as an ingredient active: [Formula 18] (1-22) (1-23) (1-24) (1-25) (1-26) (1-27) (1-28) wherein Y3 represents a lower alkylene group. Element 6: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-29) to (1-35) below or a salt thereof as an ingredient active: [Formula 19] (1-29) (1-30) (1-31) (1-32) (Y33) (1-34) (1-35) wherein Y3 represents a lower alkylene group. Element 7: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-36) to (1-42) below or a salt thereof as an ingredient active: [Formula 20] (1-36) (1-37) (1-38) (1-39) (1-40) (1-41) (1-42) wherein Y3 represents a lower alkylene group. Element 8: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-43) to (1-49) below or a salt thereof as an ingredient active: [Formula 21] (1-43) (1-44) (1-45) (1-46) (1-47) (1-48) (1-49) wherein Y3 represents a lower alkylene group. Element 9: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-50) to (1-56) below or a salt thereof as an ingredient active: [Formula 22] (1-50) (1-51) (Y52) (1-53) (1-54) (1-55) (1-56) wherein Y3 represents a lower alkylene group. Element 10: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-57) to (1-63) below or a salt thereof as an ingredient active: [Formula 23] (1-57) (1-58) (1-59) (1-60) (1-61) (1-62) (1-63) wherein Y3 represents a lower alkylene group. Element 11: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-64) to (1-70) below or a salt of the misrao as an ingredient active: [Formula 24] (1-64) (1-65) (1-66) (1-67) (1-68) (1-69) (1-70) wherein Y3 represents a lower alkylene group, and Zi represents a lower alkenylene group. Element 12: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-71) to (1-77) below or a salt thereof as an ingredient active: [Formula 25] (1-71) (1-72) (1 -73) "-TO (1-74) (1-75) (1-76) (1-77) wherein Y3 represents a lower alkylene group. Element 13: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-78) to (1-84) below or a salt thereof as an ingredient active: [Formula 6 to 6] (1-78) (1-79) (1-80) (1-81) (1-82) (1-83) (1-84) wherein Y3 represents a lower alkylene group. Element 14: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-85) to (1-91) below or a salt thereof as an ingredient active: [Formula 27] (1-85) (1-86) (1-87) n-A (1-88) (1-89) (1-90) (1-91) wherein Y3 represents a lower alkylene group. Element 15: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-92) to (1-98) below or a salt thereof as an ingredient active: [Formula 28] (1-95) (1-96) (1-97) (1 -98) wherein Y3 represents a lower alkylene group. Element 16: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-99) to (1-105) below or a salt thereof as an ingredient active: [Formula 2 9; (1-99) (1-100) (1-101) (1-102) (1-103) (1-104) (1-105) wherein Y3 represents a lower alkylene group. Element 17: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-106) to (1-112) below or a salt thereof as an ingredient active: [Formula 30] -TO (1-106) (1-107) (1-108) (1-109) (1-110) (1-1 11) (1-112) wherein Y3 represents a lower alkylene group. Element: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-113) to (1-119) below or a salt thereof as an ingredient active: [Formula 31] 1-113) (1-114) (1-115) (1-116) (1-117) (1-118) (1-119) wherein Y3 represents a lower alkylene group. Element: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-120) to (1-126) below or a salt thereof as an ingredient active: [Formula 32] (1-120) (1-121) (1-122) (1-123) (1-124) (1-125) (1-126) wherein Y3 represents a lower alkylene group, and Z represents a lower alkynylene group. Element: The antineoplastic agent according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-127) to (1-133) below or a salt of the misrao as an ingredient active: [Formula 33] (1-127) (1-128) (1-129) n -A (1-130) (1-131) (1-132) (1-133) wherein Y3 represents a lower alkylene group. Element: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-134) to (1-140) below or a salt thereof as an ingredient active: [Formula 34] (1-134) (1-135) (1-136) (1-137) (1-138) (1-139) (1-140) wherein Y3 represents a lower alkylene group, and Z3 represents a lower alkylene group or a -N (R8d) - group. Element 22: The antineoplastic agent according to any of items 1 to 21, wherein Y is a group -0-. Element 23: The antineoplastic agent according to any of items 1 to 21, where Y is a group -N (R5) - • Element 24: The antineoplastic agent according to any of items 1 to 21, where Y is a group -CO-, a group -CH (OH) -, a lower alkylene group, a -S (0) n- group, or a -C (= N-OH) - group. Element 25: The antineoplastic agent according to any of items 1 to 21, wherein A is a group [Formula 35] , Element 26: The antineoplastic agent according to any of items 1 to 21, wherein A is a group [Formula 36] Element 27: The antineoplastic agent according to any of items 1 to 21, wherein R 4 represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group , a 1, 2, 5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring, a 3, 5-dioxoisoxazolidin-4-ylidene group lower alkyl, a 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a group thiazolidinyl lower alkyl which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 37] ^ N-R13 or a group [Formula 38] Element 28: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)? - N (R14) R15, and 1 is 0. Element 29: The antineoplastic agent according to either of elements 1 to 21, wherein R4 is a group - (T) XN (R14) R15, and 1 is 1. Element 30: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)! - N (R14) R15, 1 is 1, and T is a group -N (R17) -B3-CO-. Element 31: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)? - N (R14) R15, 1 is 1, and T is a group -B19-N (R18 ) -CO-. Element 32: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)? ~ N (R14) R15, 1 is 1, and T is a group -B4-CO-.

Element 33: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a group -Q-B5-CO-. Element 34: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)? - N (R1) R15, 1 is 1, and T is a group -B6-N (R19 ) -B7-. Element 35: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)! -N (R14) R15, 1 is 1, and T is a group -CO-B8-. Element 36: The antineoplastic agent according to any of the elements 1 to 21, wherein R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a group -CH (OH) -B9-. Element 37: The antineoplastic agent according to any of items 1 to 21, wherein R 4 is a group - (T) X-N (R 14) R 15, 1 is 1, and T is a group -CO-B 10 -CO-. Element 38: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)? - N (R14) R15, 1 is 1, and T is a group -CH (OH) - Bu-CO-. Element 39: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T)! -N (R14) R15, 1 is 1, and T is a -CO- group. Element 40: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a -S02- group. Element 41: The antineoplastic agent according with any of elements 1 to 21, wherein R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a group -B23a-CO-CO-. Element 42: The antineoplastic agent according to any of items 1 to 21, wherein R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a lower alkylene group. Element 43: The antineoplastic agent according to item 1, which comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-1), (1-2), (1-8), (1 -9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58) ), (1-64) and (1-65) or a salt thereof as an active ingredient, wherein Y is a group -O- or a group -N (R5) -, A is a group [Formula 39- 1] D R4 is a group - (T) X-N (R14) R15. Element 44: The antineoplastic agent according to element 43, wherein 1 is 1, and T is a group -N (R17) -B3-CO-. Element 45: The antineoplastic agent according to element 43, wherein 1 is 1, and T is a group -B-CO-. Element 46: The antineoplastic agent according to element 43, wherein 1 is 1, and T is a group -CO-.

Element 47: The antineoplastic agent according to element 43, wherein 1 is 0. Element 48: The antineoplastic agent according to element 1, comprising a compound selected from the group consisting of N- [6- (4- {. [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-methoxyphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4- ([2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino] phenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- { [2- ( 4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino.} -2-fluorophenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- { [2- (4- piperonylpiperazin-1-yl) -2-oxoethyl] methylamino.} -2-fluorophenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- ([2- (4-piperonylpiperazine-1- il) -2-oxoethyl] methylamino.} -2-methoxyphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino.} -2-methoxyphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4-. { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-methylphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino}. -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- (6-. {4- [3- (4-piperonylpiperazin-1-yl) -3-oxopropyl] phenoxy] pyridin-3 -yl) -3,4-dichlorobenzenesulfonamide, N- [6- (4- {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperazin-1-yl} phenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4-. {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} phenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N-. { 6- [(4- (4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl] phenyl) methylamino] pyridin-3-yl} -4-trifluoromethylbenzamide N- [6- (4- { 4- [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- (4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin-3 il] -4-trifluoromethylbenzamide, N- [6- (4-. {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- (6- [4- (-benzylpiperazin-1-carbonyl) phenoxy] pyridin-3-yl.} -4-trifluoromethylbenzamide, N- (6- [ 4- (4-benzylpiperazine-1-carbonyl) phenoxy] pyridin-3-yl.} - 3, 4-dichlorobenzamide, N- [6- (. {4- [3- (4-piperonylpiperazin-1-yl) ) -3-oxopropyl] phenyl.}. Methylamino) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl ] ethylamino.} -2-fluorophenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4-. [2- (-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-fluorophenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino}. -2-methoxyphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino}. phenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, 1- (6- (4- [3- (4-piperonylpiperazin-1-yl) -3-oxopropyl] phenoxy], pyridin-3-yl) -3- (3,4-dichlorophenyl) -1- ethylurea, N- (6- (4- [3- (4-piperonylpiperazin-1-yl) -3-oxopropyl] phenoxy] pyridin-3-yl) -4-trifluoromethylbenzamide, N- [6- (4- { [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethyl-benzamide, N- [6- (4- (4 - [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl}. Phenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- (6-. {4 - [3- (4-piperonylpiperazin-1-carbonyl) piperidin-1-yl] phenoxy] pyridin-3-yl) -3,4-dichlorobenzamide, N- [6- (4 - (4- [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl}. Phenoxy) pyridin-3-yl] -4-trifluoromethyl-benzamide, N-. {6 - [(4-. {4 - [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl}. Phenyl) methylamino] pyridin-3-yl.} -4-trifluoromethylbenzamide, N- (6-. { . - [(2- (4- [4- (4-fluorobenzoyl) phenyl] piperazin-1-yl} -2-oxoethyl) methylamino] -2-methoxyphenoxy] pyridin-3-yl) -4- trifluoromethylbenzamide, 2- (4-piperonylpiperazin-1-yl) -N-. {3-methyl-4- [5- (4-trifluoromethyl-phenoxymethyl) il) pyridin-2-yloxy] phenyl} -2-oxoacetamide, N- [6- (4- { [2 - (4 -piperoni lpiperazin-1 -i 1) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3 il] -2-fluoro-4-trif luoromethylbenzamide, N- [6- (4 - { - [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl}. 2-methoxyphenoxy) pyridin-3-yl] -4-trif luoromethylbenzamide and 4 - (3. {3-met il-4 - [5- (4-tri fluoromethylbenzoylamino) pyridin-2-yloxy) ethyl ester ] phenyl.}. -2- oxohexahydropyrimidin-1-yl) benzoic acid, or a salt thereof as an active ingredient. Element 49: The antineoplastic agent according to any of items 1 to 48, wherein a target of the antineoplastic agent is a malignant tumor. Element 50: The antineoplastic agent according to element 49, wherein the malignant tumor is a solid turaor. Eleraento 51: The antineoplastic agent according to item 49, wherein the malignant tumor is a hematologic cancer. Element 52: The antineoplastic agent according to item 49, wherein the malignant tumor is lymphoma, leukemia, or myeloma. Element 53: A method for treating or preventing tumors, comprising the administration of a compound represented by the general formula (1) below or a salt thereof: [Formula 39-2] wherein Xi represents a nitrogen atom or a group -CH =, R1 represents a group -Z-R6, Z represents a group -N (R8) -B-, a group -B-N (R8) -, a group -B0-O-, a group [Formula 39-3] -NHCO- SL a group -CO-, a group -CH (OH) -, a group -N (R9a) -CO-N- (R9b) -, a group -N = CH-, a group -N (R10a) -S02- (B22a) e-, a lower alkenylene group, a group -NHCO-Bi-, a group -NHCO-B2- (W) u-, a group -BO-0-B? Ga-, a group [Formula 39- 4] (CH2) k , a group [Formula 39-5] -N N- (B2? A) c- , a -S02-N (R) -, a -S- group, a lower alkynylene group, a lower alkylene group, a -N (R8d) - or a -CO-NH-Bisa-R8 group represents a hydrogen atom, a lower alkyl group which may have a lower alkoxy group as a substituent, a lower alkanoyl group, a group lower alkylsulfonyl or a phenyl lower alkyl group, B represents a -CO- group or a lower alkylene group, Bo represents a lower alkylene group, Bi represents a lower alkenylene group which may have a phenyl group as a substituent, B2 represents an alkylene group which can be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group, R9a represents a hydrogen atom or a lower alkyl group, R represents a hydrogen atom or a lower alkyl group, R10a represents a hydrogen atom or a lower alkyl group, B22a represents a lower alkylene group or a lower alkenylene group, e represents 0 or 1, Bißa represents a lower alkylene group, Biga represents a lower alkylene group, B2oa represents a lower alkylene group, B2 represents a lower alkylene group, k represents 2 or 3, c represents 0 or 1, d 'represents 0 or 1, R10b represents a hydrogen atom or a lower alkyl group, R8d represents a hydrogen atom or a lower alkyl group, represents an oxygen atom, a group -NH-, or a sulfur atom, u represents 0 or 1, R6 represents a heterocyclic group of 5 to 15 monocyclic, dicyclic members or saturated or unsaturated tricyclic having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (which may have 1 to 3 substituents, which are selected from the group consisting of an oxo group); a lower alkoxy group which may have a halogen atom as a substituent; a lower alkyl group which may have a halogen atom corao a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group which may be substituted by a lower alkyl group which may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantyl group, a naphthyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), an alkyl group which may have a lower alkoxy group as a substituent, a cycloalkyl group which may be substituted by a group selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have a halogen atom as a substituent, in the cycloalkyl ring, a lower alkenyl group which may have a halogen atom such as a substituent, a lower alkanoyl group, a benzoyl group (which may have 1 to 3 groups selected from the group consists of a lower alkyl group which may have a halogen atom and a halogen atom, as a substituent, on the phenyl ring), a lower alkyl group substituted with halogen atom, cycloalkyl lower alkyl group or a group [Formula 39-6] 7) m R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, an halogen, a lower alkyl group which may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group which may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group, a cyano group, a lower alkanoyl group which may have a halogen atom as a substituent, a group lower alkylsulfonyl, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a saturated or unsaturated 5- or 6-membered heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or atoms of sulfur (which may have an oxo group in the heterocyclic ring), m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R 7s may be identical or different) and R 2 represents a hydrogen atom, a halogen atom, or a lower alkyl group, Y represents a group -O-, a group -N (R 5) -, a group -CO-, a group -CH (OH) -, a lower alkylene group, a -S (0) n- group, or a group -C (= N-OH) -, R5 represents a hydrogen atom, a lower alkyl group, a group lower alkanoyl, a group benzoyl, a phenyl lower alkyl group, or a cycloalkyl group, n represents 0, 1 or 2, A represents a group [Formula 39-7] or a group [Formula 39-8] p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a - CONRuR12, or a cyano group, wherein R11 and R12 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R11 and R12, together with the nitrogen to which they bind, can bind to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, R 4 represents an imidazolyl lower alkyl group, a 1,2-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl alkyl group lower, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4- oxadiazolyl lower alkyl which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 39 -9] , a group [Formula 39-10] or a group - (T) X-N (R14) R15, R, 1X3J represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl imidazolyl group, a group lower alkoxycarbonyl lower alkyl, a carboxy lower alkyl group, a benzoyl group, a lower alkanoyl group substituted with morpholino, a piperazinyl carbonyl lower alkyl group which may be substituted, on the piperazine ring, by a phenyl lower alkyl group which may have a lower alkyl group; lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkyl group which may be substituted, on the piperazine ring, by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a group lower alkyl substituted with morpholinocarbonyl, or an imidazolyl alkane group lower ilo, R13a represents a hydrogen atom or a hydroxyl group, T represents a lower alkylene group, a group -N (R17) -B3-CO-, a group -B19-N (R18) -CO-, a group - B4-CO-, a group -Q-B5-CO-, a group -B6-N (R19) -B7-C0-, a group -CO-B8-, a group -CH (0H) -B9-, a group group -CO-B? 0-CO-, a group -CH (OH) -Bu-Cu-, a group -CO-, a group -S02-, or a group -B23a_CO-CO-, wherein R 17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkenyl group, a lower alkanoyl group substituted with amino that may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group, B3 represents a lower alkylene group, B19 represents a lower alkylene group, R18 represents a hydrogen atom or a lower alkyl group, B represents a lower alkenylene group or a lower alkylene group which may have a hydroxyl group as a substituent, Q represents an oxygen atom or a group -S (0) n- (where n is equal to that described above), B5 represents a lower alkylene group, B6 represents a lower alkylene group, R19 represents a hydrogen atom or a lower alkanoyl group, B7 represents a lower alkylene group, B8 represents a lower alkylene group, Bg represents a lower alkylene group, Bio represents a lower alkylene group, Bu represents a lower alkylene group, B23a represents a lower alkylene group, 1 represents 0 or 1, R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents (2) an alkyl group substituted with a hydroxyl group, (3) a cycloalkyl group which may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (A) a phenoxy lower alkyl group, (5) a phenyl group which may be substituted, on the phenyl ring , by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; a lower alkoxy amino group which may have a lower alkyl group as a substituent; a lower alkyl group substituted with a hydroxyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the ring piperazine; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group having a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkyl group substituted with lower alkoxycarbonyl , (11) a lower alkyl group substituted with carboxy, (12) an amino group which may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group which may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent (s) on the tetrahydroquinoline ring, (14) a lower alkyl cycloalkyl group, (15) a lower alkyl piperazinyl group which p can be substituted, in the piperazine ring, by a phenyl lower alkyl group which can have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a lower alkyl pyridyl group, (17) a lower alkyl group substituted with a amino group that can have a selected group of a group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a lower alkyl group substituted with 1,2,3,4-tetrahydroisoquinolylcarbonyl, (22) a piperidinylcarbonyl group which may have a group selected from the group consisting of a lower alkoxycarbonyl group, a lower alkyl phenyl group, and a lower alkyl furyl group as a substituent in the piperidine ring, (23) a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group which may be substituted, on the piperidine ring, by a group selected from the group consisting of group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a lower alkyl furyl group, (25) an alkyl carbonyl group inf erior replaced by a group [Formula 39-11] , (26) a lower alkyl carbonyl group substituted by a group [Formula 39-12] d (27) a group -CO-B20-N p R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a morpholino lower alkyl group, (28a) a phenyl lower alkenyl group, (29a) an anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the ring phenyl, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group which may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may be having a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group which may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group which may have a group lower alkyl as a substituent on the carbazole ring, (35a) an amidino group which may have a lower alkyl group as a substituent, (36a) an oxalyl group substituted with piperazinyl which may having 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent (s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent (s) on the piperazine ring, or (37a) a lower alkyl group substituted with cyano, R34 represents an oxo group or a phenyl group, d represents an integer from 0 to 3, B2o represents a lower alkylene group, R36 and R37, together with the nitrogen atom at which are joined, can be linked to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 3 phenyl lower alkyl groups which can have a lower alkylenedioxy group on the phenyl ring, can be present as a substituent (s), R14 and R15, together with the nitrogen atom to which they are attached, can be attached to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated or unsaturated 5-10 membered heterocyclic ring; or a group [Formula 39-13] i -N V wherein, in the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consists of (28) a lower alkyl group substituted with phenyl, having 1 to 2 phenyl groups which can be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group which can be having a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, and which may have a pyridyl group in the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group which may have, as a substituent (s) in the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a group hydroxyl as a substituent, (31) a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl group lower alkyl, (34) a furyl lower alkyl group, (35) a benzoyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group which can have a group lower alkylsulfonyl as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring , a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a piperazinyl group, (38) a pyridyl group, (39) ) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkyl group which may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group [Formula 39-14] Ra = N-N = * (Rb (wherein Ra and Rb each represents a lower alkyl group), (41) a lower alkyl group which may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a group lower alkanoyl which may have a halogen atom as a substituent, (43) a phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom corao a substituent, a benzoyl group which may have a halogen atom as a substituent on the ring phenyl, a phenyl lower alkyl group which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) ) a naphthyl lower alkyl group, (46) a phenoxy group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a group c iano, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a lower alkoxy phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which can have a halogen atom as a substituent, (49) a group - (B? 2CO) t-N (R20) R21, (50) a group - (C0) or -B? 3- N (R22) R23, (51) a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which can be substituted, on the 1, 2, 3, 4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent (s), (52) a cycloalkyl group which can having a hydroxyl group as a substituent, (53) a piperidinyl group which may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent (s), (54) a lower alkyl quinolyl group, (55) ) a 1,2,3,4-tetrazolyl lower alkyl group which may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl group lower alkyl which may have a phenyl group as a substituent on the thiazole ring, (57) a lower alkyl benzoyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent (s) in the phenyl ring, (58) a group piperidinyl lower alkyl which may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group which may have 1 to 3 phenyl groups as a substituent (s) on the imidazole ring, (60) a group benzimidazolyl which may have 1 to 3 lower alkyl groups as a substituent (s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the ring of tetrahydroquinoline, (63) a 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, (64) a lower alkyl cycloalkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy alkanoyl group lower, (76) a 1, 2, 3, 4-tetrahydroquinolylcarbonyl group which may have an oxo group or a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) an imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) ) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group - (O-B15) s-CO-N (R26) R27, (85) an -N (R28) -CO group -B? 6-N (R29) R30, (86) a group -N (R31) -B? 7 -CO-N (R32) R33, (87) a benzoxazolyl group, (88a) a group benzothienyl, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, B12 represents a lower alkylene group, t represents 0 or 1, R20 and R21 can be identical or different and each represents a hydrogen atom; an amino group which may have a lower alkoxycarbonyl group as a substituent; a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group that can having 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent on the pyrrolidine ring; a lower alkyl group substituted with amino which may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as a substituent (s) on the 1, 2, 3, 4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a lower alkyl pyridyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent (s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group; a phenoxy lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group or a substituent (s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group which may have a halogen atom as a substituent; a lower alkanoyl imidazolyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a lower alkyl carboxy group, or a cycloalkyl group; and R20 and R21, together with the nitrogen atom to which they are attached, they can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group which may have 1 to 3 groups selected from the group consisting of a halogen atom and a group lower alkyl which may have a halogen atom as a substituent (s) on the phenyl ring, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), or represents 0 or 1, B13 represents a lower alkylene group, R22 and R23 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a benzoyl group which may have 1 to 3 lower alkoxy groups as a n substituent (s) on the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R22 and R23, together with the atom of nitrogen to which they are attached, they can bind to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have an alkylenedioxy group lower as a substituent on the phenyl ring), B15 represents a lower alkylene group, s represents 0 or 1, R26 and R27 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group , or an imidazolyl lower alkyl group, and R26 and R27, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, (wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups which may have a lower alkylenedioxy group as a substituent, may being present in the phenyl ring, as a substituent (s)), R28 represents a hydrogen atom or a lower alkyl group, Bi6 represents a lower alkylene group, R29 and R30, together with the nitrogen atom to which they are attached, can join each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, R31 represents a hydrogen atom or a lower alkyl group, BX7 represents a lower alkylene group, R32 and R33, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and an alkyl phenyl group. lower, which can have a lower alkylenedioxy group as a substituent on the phenyl ring), provided that the aforementioned compound or a salt thereof satisfies the following requirements (i) to (v): (i) when Xi represents a group - CH =, then R3 represents a hydrogen atom; (ii) when Xi represents a group -CH =, 1 represents 1, T represents -CO-, and R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents the group (24); (iii) when Xi represents a group -CH =, 1 represents 1, and T represents -N (R17) -B3-CO-, R14 and R15, together with the nitrogen atom to which they are attached, can bind to each other , directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated or unsaturated 5- to 10-membered heterocyclic ring, wherein, in the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent (s); (iv) when Xi represents a nitrogen atom, and 1 represents 0, or when Xi represents a nitrogen atom, 1 represents 1, and T represents -CO- or -S02, R15 is not a group (5), (7) ), (19), or (20); and (v) when Rd represents a cycloalkyl group which may have on the cycloalkyl ring, a substituent selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have one atom of halogen as a substituent, R4 represents a group - (T) iN (R14) R15 (wherein T and 1 are the same as those described above, and R14 and R15, together with the nitrogen atom to which they bind, they can bind to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 10 members; or R14 and R15 form a group [Formula 39-15] Element 54: Use of a compound represented by the general formula (1) below or a salt thereof to make an antineoplastic agent: [Formula 39-16] wherein Xx represents a nitrogen atom or a group -CH =, R1 represents a group -Z-R6, Z represents a group -N (R8) -B-, a group -BN (R8) -a group -B0- O-, a group [Formula 39-17] -NHCO- SL a group -CO-, a group-CH (OH) -, a group -N (R9a) -CO-N- (R9b) -, a group -N = CH-, a group -N (R10a) -S02- (B22a) e-, a lower alkenylene group, a group -NHCO-Bi-, a group -NHCO-B2- () u-, a group -BO-0-B? ga-, a group [Formula 39-18] , a group [Formula 39-19] -N N- (B2? A) c- , a group -S02-N (R10b) -, a group -S-, a lower alkynylene group, a lower alkylene group, a group -N (R8d) - or a group -C0-NH-Bl8a-- R8 represents a hydrogen atom, a lower alkyl group which may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a lower alkyl phenyl group, B represents a -CO- group or a lower alkylene group, B0 represents a lower alkylene group, Bi represents a lower alkenylene group which may have a phenyl group as a substituent, B2 represents a lower alkylene group which can be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group, R9a represents a hydrogen atom or a lower alkyl group, R9b represents a hydrogen atom or an alkyl group lower, R10a represents a hydrogen atom or a lower alkyl group, B22a represents a lower alkylene group or a lower alkenylene group, e represents 0 or 1, Bisa represents a lower alkylene group, B? ga represents a lower alkylene group, B2oa represents a lower alkylene group, B2 represents a lower alkylene group, k represents 2 or 3, c represents 0 or 1, d 'represents 0 or 1, R10b represents a hydrogen atom or a lower alkyl group, R8d represents a hydrogen atom or a lower alkyl group, W represents an oxygen atom, a group -NH-, or a sulfur atom, u represents O or 1, R6 represents a 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (which may have 1 to 3 substituents, which are selected from the group consisting of an oxo group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkyl group which may have a halogen atom as a substituent, a halogen atom, an alkylsulfonyl group lower, a phenyl group which may be substituted by a lower alkyl group which may have a halogen atom on the phenyl ring, a lower alkylthio group, a pyrrolyl group, a benzoyl group, a lower alkanoyl group, a lower alkoxycarbonyl group, and a lower alkyl group; amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent on the heterocyclic ring) , an adamantyl group, a naphthyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of an alkyl group lower and a lower alkanoyl group as a substituent, on the naphthalene ring), an alkyl group which may have a lower alkoxy group as a substituent, a cycloalkyl group which may be substituted by a group selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have a halogen atom as a substituent, on the cycloalkyl ring, a lower alkenyl group which may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkyl group which may have a halogen atom and an atom of halogen, as a substituent, on the phenyl ring), a lower alkyl group substituted with halogen atom, cycloalkyl lower alkyl group or a group [Formula 39-20] R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group which may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group, a cyano group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a saturated or unsaturated 5- or 6-membered heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (which may have an oxo group in the heterocyclic ring), m represents an integer from 1 to 5 (when m represents 2 to 5, two to five Rs may be identical or different) and R2 represents a hydrogen atom, a halogen atom, or a lower alkyl group, Y represents a group -0-, a group -N (R5) -, a group -CO-, a group -CH (OH) -, an lower alkylene group, a group -S (0) n-, or a group -C (= N-0H) -, R5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a group phenyl lower alkyl, or a cycloalkyl group, n represents 0, 1, or 2, A represents a group [Formula 39-21] or a group [Formula 39-22] p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a - CONR ^ R12, or a cyano group, wherein R11 and R12 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R11 and R12, together with the The nitrogen atom to which they are attached may be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, R4 represents an alkyl imidazolyl group lower, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl alkyl group lower, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4- oxadiazolyl lower alkyl which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 39 -2. 3] , a group [Formula 39-24] or a group - (T)? -N (R14) R15, R > 1X3J represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxyl lower alkyl group, a benzoyl group, a lower alkanoyl group substituted with morpholino, a piperazinyl carbonyl lower alkyl group which may be substituted, in the piperazine ring, for a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkyl group which may be substituted, on the piperazine ring, by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl group substituted with raorfolinocarbonyl, or a lower alkanoyl imidazolyl group, R13a represents a hydrogen atom or a hydroxyl group, T represents a lower alkylene group, a -N group R17) -B3-CO-, a group -B19-N (R18) -CO-, a group -B4-CO-, a group -Q-B5-CO-, a group -B6- N (R19) -B7-CO-, a group -CO-B8-, a group -CH (0H) -B9-, a group -CO-B? 0-CO-, a group -CH (OH) -Bn -CO-, a group -CO-, a group -S02-, or a group -B23a-CO-CO-, wherein R17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group which may have a halogen atom as a substituent, a group lower alkenyl, a lower alkanoyl group substituted with amino which may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group, B3 represents a lower alkylene group, Big represents a lower alkylene group, R18 represents a hydrogen atom or a group lower alkyl, B4 represents a lower alkenylene group or a lower alkylene group which may have a hydroxyl group as a substituent, Q represents an oxygen atom or a group -S (O) n- (where n is equal to that described above) , B5 represents a lower alkylene group, B6 represents a lower alkylene group, R19 represents a hydrogen atom or a lower alkanoyl group, B7 represents a lower alkylene group, Bs represents a lower alkylene group, B9 represents a lower alkylene group, Bio represents a lower alkylene group, Bu represents a lower alkylene group, B23a represents a lower alkylene group, 1 represents 0 1, R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents (2) an alkyl group substituted with a hydroxyl group, (3) a cycloalkyl group which may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a group phenoxy lower alkyl, (5) a phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; a lower alkoxy amino group which may have a lower alkyl group as a substituent; a lower alkyl group substituted with a hydroxyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which can have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group having a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkyl group substituted with lower alkoxycarbonyl, (11) a lower alkyl group substituted with carboxy, (12) an amino group which may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group which may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group corao a substituent (s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkyl group which can be substituted, on the piperazine ring, by a phenyl lower alkyl group which can have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a lower alkyl pyridyl group, (17) a lower alkyl group substituted with an amino group which can have a group selected from the group consisting of a group lower alkyl and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) an alkyl group lower substituted with 1,2,3,4-tetrahydroisoquinolylcarbonyl, (22) a piperidinylcarbonyl group which may have a group selected from the group consisting of a lower alkoxycarbonyl group, a lower alkyl phenyl group, and a lower alkyl furyl group as a substituent in the piperidine ring, (23) a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group which may be substituted, on the piperidine ring, by a selected group of the group consisting of a lower alkoxycarbonyl group, a lower alkyl phenyl group, a lower alkyl group, a benzoyl group, and a lower alkyl furyl group, (25) a lower alkyl carbonyl group substituted by a group [Footnote 39-25] , (26) a lower alkyl carbonyl group substituted by a group [Formula 39-26] [27) a group -CO-B20-N (R36) R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a lower alkyl morpholino group, (28a) a phenyl lower alkenyl group, (29a) an anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group which may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group which may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group which may have an alkyl group lower as a substituent on the carbazole ring, (35a) an amidino group which may have a lower alkyl group as a substituent, (36a) an oxalyl group substituted with piperazinyl which may have 1 to 3 groups selected from the group consisting of phenyl lower alkyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent (s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent (s) on the piperazine ring, or (37a) a lower alkyl group substituted with cyano, R34 represents an oxo group or a phenyl group, d represents an integer from 0 to 3, B20 represents a lower alkylene group, R36 and R37, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a group 5 to 7 membered saturated heterocyclic, wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups which may have a lower alkylenedioxy group on the phenyl ring, may be present as a substituent (s), R14 and R15, together with the nitrogen atom to which they are attached, they can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated or unsaturated 5- to 10-membered heterocyclic ring; or a group [Formula 39-27] wherein, in the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a lower alkyl group substituted with phenyl, having 1 to 2 phenyl groups which may be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a group cyano, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group , a hydroxyl group, and a lower alkylenedioxy group, and which may have a pyridyl group in the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group which may have, as a substituent (s) in the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a furyl lower alkyl group, (35) a benzoyl group that can be substituted,in the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group which may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may be having a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group which may have a group oxo as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a piperazinyl group, (38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a group thiazolidinyl lower alkyl which may be substituted, in the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group [Formula 39-28] Ra = N-N = _ Rb (wherein Ra and Rb each represents a lower alkyl group), (41) a lower alkyl group which may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a group lower alkanoyl which may have a halogen atom as a substituent, (43) a phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of A group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have one atom of halogen as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of in a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a group lower alkoxy phenyl which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (49) a group - (B? 2CO) tN (R20) R21, (50) a group - (CO) or B? 3 -N (R) R23, (51) a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which can be substituted, on the ring of 1, 2, 3, -tetrahydronaphthalene, by 1 to 5 lower alkyl groups as a substituent (s), (52) a group cycloalkyl which may have a hydroxyl group as a substituent, (53) a piperidinyl group which may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent (s), (54) a lower alkyl quinolyl group , (55) a 1,2,3,4-tetrazolyl lower alkyl group which may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring, (57) a lower alkyl benzoyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent (s) on the phenyl ring, (58) a piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group which may have 1 to 3 phenyl groups as a substituent (s) on the imidazole ring, (60) a benzimidazolyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, ( 62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4- ring oxadiazole, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring, (68) ) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, ( 74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1, 2, 3, 4-tetrahydroquinolylcarbonyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) an imidazolyl lower alkanoyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a group carboxy lower alkyl, (84) a group - (O-B15) s- CO-N (R26) R27, (85) a group -N (R28) -CO-B? 6-N (R29) R30, (86) a group -N (R31) -B? 7-CO-N ( R32) R33, (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent in the tetrahydroquinoline ring, B? 2 represents a lower alkylene group, t represents 0 or 1, R20 and R21 may be identical or different and each one represents a hydrogen atom; an amino group which may have a lower alkoxycarbonyl group as a substituent; a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group which may have 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent on the pyrrolidine ring; a lower alkyl group substituted with amino which may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as a substituent (s) on the 1,2,3-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a lower alkyl pyridyl group; a quinolyl lower alkyl group; a 1,2,3-tetrazolyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent (s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group; a phenoxy lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent (s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group which may have a halogen atom as a substituent; a lower alkanoyl imidazolyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a lower alkyl carboxy group, or a cycloalkyl group; and R20 and R21, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 7. members (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group it consists of a lower alkyl group, a phenyl group which may have 1 to 3 groups selected from the group consisting of a halogen atom and a lower alkyl group which may have a halogen atom as a substituent (s) on the phenyl ring, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), or represents 0 or 1, B13 represents a lower alkylene group, R22 and R23 may be identical or different and each represents an hydrogen, a lower alkyl group, a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R22 and R23, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), B15 represents a lower alkylene group, s represents 0 or 1, R26 and R27 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or a lower alkyl imidazolyl group, and R26 and R27, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, (wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups which may have a lower alkylenedioxy group as a substituent, may be present on the phenyl ring, as a substituent (s)), R28 represents a hydrogen atom or a lower alkyl group, Bi6 represents a lower alkylene group, R29 and R30, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom geno, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a group phenyl, and a phenyl lower alkyl group that can have a group lower alkylenedioxy as a substituent on the phenyl ring, R31 represents a hydrogen atom or a lower alkyl group, Biv represents a lower alkylene group, R32 and R33, together with the nitrogen atom to which they are attached, can bind to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), provided that the aforementioned co-tax or a salt thereof satisfies the following requirements (i) to (v): (i) when Xi represents a group -CH =, then R3 represents a hydrogen atom; (ii) when Xx represents a group -CH =, 1 represents 1, T represents -CO-, and R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents the group (24); (iii) when Xi represents a group -CH =, 1 represent 1, and T represent -N (R17) -B3-CO-, R14 and R15, together with the nitrogen atom to which they are attached, can bind to each other, directly or through a nitrogen atom, atom oxygen, or sulfur atom to form a saturated or unsaturated 5- to 10-membered heterocyclic ring, wherein, in the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent (s); (iv) when Xi represents a nitrogen atom, and 1 represents 0, or when Xx represents a nitrogen atom, 1 represents 1, and T represents -CO- or -S02, R15 is not a group (5), (7) ), (19), or (20); and (v) when Rd represents a cycloalkyl group which may have on the cycloalkyl ring, a substituent selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have one atom of halogen as a substituent, R4 represents a group - (T) iN (R14) R15 (wherein T and 1 are the same as those described above, and R14 and R15, together with the nitrogen atom to which they are attached, can bind one to the other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 10 merobes, or R14 and R15 form a group [Formula 39-29] Element 55: Use according to element 54, wherein one objective of the antineoplastic agent is a malignant tumor. Element 56: Use according to item 55, wherein the malignant tumor is a solid tumor. Element 57: Use according to item 55, wherein the malignant tumor is a hematologic cancer. Element 58: Use according to item 55, wherein the malignant tumor is lymphoma, leukemia or myeloma. Element 59: The antineoplastic agent according to any of elements 44 to 47, wherein R14 and R15, together with the nitrogen atom to which they are attached, are bound to each other, directly or via a nitrogen atom for forming a saturated 6-membered heterocyclic group which is substituted, in the heterocyclic ring, by a lower alkyl group substituted with phenyl which can be substituted, on the phenyl ring, by 1 or 2 group (s), as substituent (s), selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, an phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom corao a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group. Element 60: The antineoplastic agent according to item 59, wherein the saturated heterocyclic group is a piperazinyl group which is substituted by a lower alkyl group substituted with phenyl which is substituted by a lower alkylenedioxy group on the phenyl ring. Element 61: The antineoplastic agent according to element 59 or 60, wherein Xi is a nitrogen atom and Y is an oxygen atom. Specific examples of the individual groups shown in the general formula (1) are the following. Examples of the lower alkenylene group include linear or branched alkenylene groups having 2 to 6 carbon atoms and 1 to 3 double bonds such as vinylene groups, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 2-pentenylene, 1-pentenylene, 3-pentenylene, 4-pentenylene, 1,3-butadienileno, 1,3-pentadienileno, 2-penten-4- inylene, 2-hexenylene, 1-hexenylene, 5-hexenylene, 3-hexenylene, 4-hexenylene, 3, 3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1, 3, 5-hexatrienylene, 1, 3-hexadienylene, and 1,4- hexadienylene. Examples of the lower alkynylene group include linear or branched alkynylene groups having 2 to 6 carbon atoms and 1 to 3 triple bonds such as ethynylene, 1-propynylene, 1-methyl-1-propynylene, 2-methyl-1-propynylene groups, 2-propynylene, 2-butynylene, 1-butynylene, 3-butynylene, 2-pentynylene, 1-pentynylene, 3-pentynylene, 4-pentynylene, 2-pentyne-4-inylene, 2-hexynylene, 1-hexynylene, 5- hexinylene, 3-hexinylene, 4-hexinylene, 3, 3-diethyl-1-propynylene, and 2-ethyl-1-propynylene. Examples of the lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, and hexyloxy groups. Examples of the lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, 2,2-dimethylpropyl, 1-ethylpropyl, butyl, isobutyl, tertbutyl, isopentyl, pentyl, and hexyl. Examples of the lower alkyl group which may have a lower alkoxy group as a substituent include, in addition to the lower alkyl groups described above, linear or branched alkyl groups having 1 to 6 carbon atoms which may have a straight or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as methoxymethyl, 1-ethoxyethyl, 2-methoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1, l-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl groups, and 3-methoxypropyl. Examples of the lower alkanoyl group include linear or branched alkanoyl groups having 1 to 6 carbon atoms such as the formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, and hexanoyl groups. Examples of the phenyl lower alkyl group include phenylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5- phenylpentyl, 6-phenylhexyl, 1, l-dimethyl-2-phenylethyl, and 2-methyl-3-phenylpropyl. Examples of the lower alkylene group include linear or branched alkylene groups having 1 to 6 carbon atoms such as methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethylethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, and hexamethylene. Examples of the lower alkenylene group which may have a phenyl group as a substituent include linear or branched alkenylene groups, having 2 to 6 carbon atoms and 1 to 3 double bonds, and which may have a phenyl group as a substituent such as vinylene groups, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 2-pentenylene, 1-pentenylene, 3-pentenylene, 4-pentenylene, 1,3-butadienileno, 1, 3-pentadienileno, 2-penteno-4-inileno, 2-hexenileno, 1-hexenileno, 5-hexenileno, 3-hexenileno, 4- hexenylene, 3, 3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1, 3, 5-hexatrienylene, 1, 3-hexadienylene, 1,4-hexadienylene, 1-phenylvinylene, 3-phenyl-1 propenylene, 3-phenyl-1-methyl-1-propenylene, 3-phenyl-2-methyl-1-propenylene, 1-phenyl-2-propenylene, 1-phenyl-2-butenylene, 3-phenyl-1-butenylene, 1-phenyl-3-butenylene, 5-phenyl-2-pentenylene, 4-phenyl-1-pentenylene, 2-phenyl-3-pentenylene, 1-phenyl-4-pentenylene, 1-phenyl-1,3-butadienylene, 1-phenyl-1,3-pentadienylene, 1-phenyl-2-penten-4-inylene, 1-phenyl-2-hexenylene, 3-phenyl-1-hexenylene, 4-phenyl-5-hexenylene, 6-phenyl- 3-hexenylene, 5-phenyl-4-hexenylene, 1-phenyl-3, 3-dimethyl-1-propenylene, 1-phenyl-2-ethyl-1-propenylene, 6-phenyl-1,3,5-hexatrienylene, 1-phenyl-1,3-hexadienylene, and 2-phenyl-1,4-hexadienylene. Examples of the lower alkylene group which can be substituted with a group selected from the group consisting of a lower alkoxy group and a phenyl group include, in addition to the lower alkylene groups described above, linear or branched alkylene groups having 1 to 6 carbon atoms which can be substituted with 1 or 2 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms and a phenyl group such as methoxymethylene, 2-phenylethylene, 3-ethoxytrimethylene, l-propoxy-2-methyltrimethylene, l-phenyl-2 groups , 2-dimethylethylene, 3-phenyl-2,2-dimethyltrimethylene, 2-butoxy-1-methyltrimethylene, phenylmethylmethylene, 2-pentyloxyethylmethylene, 4-phenyl-2-hexyloxytetramethylene, 3-phenylpentamethylene, 5-phenylhexamethylene, ethoxymethylene, 1-phenylethylene , 3-phenyltrimethylene, and 2-phenyl-1-methoxyethylene. Examples of the saturated or unsaturated, monocyclic, bicyclic or tricyclic 5- to 15-membered heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, 1,2 groups, 5,6-tetrahydropyridyl, 1, 2,4-triazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, thiazolidinyl, 1,2,3,4-tetrazolyl, thienyl, quinolyl, 1,4- dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazil, 2H-pyrrolyl, pyrrolyl, 1,3,4-oxadiazolyl, tetrahydropyranyl, tetrahydrofuryl, furazanyl, carbostyril, 3,4-dihydrocarbostyril, 1,2,3,4-tetrahydroquinolyl, 1, 2, 3, 4-tetrahydroisoquinolyl, indolyl, isoindolyl, indolinyl, benzoimidazolyl, benzooxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, quinoxalinyl, cinnolinyl, phthalazinyl, carbazoyl, acridinyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, phenothiazinyl, benzofuryl, 2,3-dihydrobenzo [b] furyl, benzothienyl, phenoxythinyl, phenoxazinyl, 4H-chromenyl, lH-indazolyl, phenazinyl, xanthenyl, thianthrenyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolyl, isooxazolidinyl, thiazolyl, isothiazolyl, pyranyl, 2-thiazolinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzooxadinyl, 3,4-dihydro-2H-1, 4-benzooxadinyl, 3,4-dihydro-2H-1, 4- benzothiazinyl, 1,4-benzothiazinyl, 1, 2, 3, 4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, fenalthridinyl, 1,4-dithiaphthalenyl, dibenz [b, e] azepine, and 6, ll -dihydro-5H-dibenz [b, e] azepine. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. Examples of the lower alkoxy group which may have a halogen atom as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as methoxy, ethoxy, propoxy groups , isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, chloropropoxy, 2,3-dichloropropoxy, 4, 4, 4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, and 5,6-dichlorohexyloxy.

Examples of the lower alkyl group which may have a halogen atom as a substituent include, in addition to the lower alkyl groups described above, linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, dichloromethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2, 3 -dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, and 5,6-dibromohexyl. Examples of the lower alkylsulfonyl group include linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, and hexylsulfonyl groups. Examples of the phenyl group which can be substituted, on the phenyl ring, with a lower alkyl group which can have a halogen atom include phenyl groups which can be substituted, on the phenyl ring, with 1 to 3 linear or branched alkyl groups which they have 1 to 6 carbon atoms which may have 1 to 3 halogen atoms such as phenyl, 2-methylphenyl, 3-methylphenyl, 4- methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2, 5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2- (bromomethyl) phenyl, 3- (2-chloroethyl) phenyl, 4- (2 , 3-dichloropropyl) phenyl, 4- (4-fluorobutyl) phenyl, 3- (5-chloropentyl) phenyl, 4- (5-bromohexyl) phenyl, 4- (5,6-dibromohexyl) phenyl, 3,4-di (trifluoromethyl) phenyl, 3,4-di (4, 4, 4-trichlorobutyl) phenyl, 2,4-di (3-chloro-2-methylpropyl) phenyl, 2,5-di (3-chloropropyl) phenyl, , 6-di (2,2,2-trifluoroethyl) phenyl, 3,4,5-tri (trifluoromethyl) phenyl, 4- (2,2,2-trichloroethyl) phenyl, 2-methyl-4-trifluoromethylphenyl, and -ethyl-4-trichloromethyl. Examples of the lower alkylthio group include linear or branched alkylthio groups having 1 to 6 carbon atoms such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, and hexylthio groups. Examples of the amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent include amino groups which may have 1 or 2 groups selected from the group consisting of linear or branched alkyl groups that have 1 to 6 carbon atoms and linear or branched alkanoyl groups having 1 to 6 carbon atoms as substituents such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylaraine, N- isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, diacetylamino, N-acetyl-N-methylamino, and N-acetyl-N-ethylamino. Examples of the naphthyl group which can be substituted on the naphthalene ring with 1 to 3 substituents selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group which can have a group selected from the group consisting of lower alkyl group and lower alkanoyl group include naphthyl groups which may have, in the naphthalene ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a halogen atom , and an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as groups (1- or 2-) naphthyl, 1- methyl- (2-, 3-, A-, 5-, 6-, 7- or 8-) naphthyl, 2-ethyl- (l-, 3-, 4-, 5-, 6-, 7- or 8 -) naphthyl, 3-n-propyl- (1-, 2-, 4-, 5-, 6-, 7-or 8-) naphthyl, 4-n-butyl- (1-, 2-, 3-, 5-, 6-, 7- or 8-) naphthyl, 4-methyl- (l-, 2-, 3-, 5-, 6-, 7- or 8-) naphthyl, 5-n-pentyl- (1 -, 2-, 3-, 4-, 6-, 7- or 8-) naphthyl, 6-n-hexyl- (1-, 2-, 3-, A-, 5-, 7- or 8-) naphthyl, 1, 7-dimethyl- (2-, 3-, A-, 5-, 6- or 8-) naphthyl, 1,2, 8-trimethyl- (3-, 4-, 5-, 6- or 7-) naphthyl, 1-dimethylamino- (2-, 3-, A-, 5-, 6-, 7- or 8-) naphthyl, 2-dimethylamino- (1-, 3-, A-, 5-, 6-, 7- or 8-) naphthyl, 3-methylamino- (1-, 2-, A-, 5-, 6-, 7- or 8-) naphthyl, 5-amino- (1-, 2-, 3-, 4-, 6-, 7- or 8-) naphthyl, 5-dimethylamino- (1-, 2-, 3-, 4-, 6-, 7- or 8-) naphthyl, 4- (N- methyl-N-ethylamino) - (1-, 2-, 3-, 5-, 6-, 7- or 8-) naphthyl, l-methyl-2-dimethylamino- (3-, A-, 5-, 6 -, 7- or 8-) naphthyl, l-chloro- (2-, 3-, 4-, 5-, 6-, 7- or 8-) naphthyl, and 1-acetylamino- (2-, 3-, A-, 5-, 6-, 7- or 8-) naphthyl. Examples of the alkyl group which may have a lower alkoxy group as a substituent include, in addition to the lower alkyl groups described above which may have a lower alkoxy group as a substituent, linear or branched alkyl groups having 1 to 8 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as corao heptyl groups, 1-ethylpentyl, octyl, 7-methoxyheptyl, 1-ethoxyheptyl, 2-propoxyl-1-ethylpentyl, 3- isopropoxyoctyl, 7-butoxyheptyl, 8-pentyloxyoctyl, and 5-hexyloxy-1-ethylpentyl. Examples of the substituted amino lower alkyl group which may have a lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1, l-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl group , methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropilaminopropilo, 4-butilaminobutilo, 5-pentilaminopentilo, 6-hexilaminohexilo, dimethylaminomethyl, 2-diethylaminoethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino) methyl, and 2 - (N-methyl-N-hexylamino) ethyl. Examples of the cycloalkyl group include cycloalkyl groups having 3 to 16 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo, cicioheptilo, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cicloteradecílo, cyclopentadecyl, cyclohexadecyl and. Examples of the cycloalkyl group which may be substituted with a group selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and an alkyl group lower which may have a halogen atom as a substituent on the cycloalkyl ring include, in addition to the cycloalkyl groups described above, cycloalkyl groups having 3 to 16 carbon atoms which may be substituted, on the cycloalkyl ring, with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms and an alkyl group linear or branched having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as 4-dimethylaminomethylcyclohexyl, 2- (aminomethyl) cyclopropyl, 3- (2-aminomethyl) cyclobutyl, 2- (l -aminoethyl) cyclopentyl, 3- (3-aminopropyl) cyclohexyl, 3- (4-aminobutyl) cycloheptyl, 4- (5-aminopentyl) cyclooctyl, 4- (6-aminohexyl) cyclohexyl, 2- (1, 1-dimethyl- 2-aminoethyl) cycloheptyl, 3- (2 -methyl-3-aminopropyl) cyclopentyl, 3- (raetilaminometil) ciciohexilo, 2- (1-ethylaminoethyl) cyclooctyl, 2- (2-propylaminoethyl) ciciohexilo, 3- (3-isopropylaminopropyl) cyclopentyl, 4- (4-butilaminobutil) cycloheptyl, 2- (5-pentylaminopentyl) cyclohexyl, 2- (6-hexylaminohexyl) cyclopentyl, 3- (dimethylaminomethyl) cyclohexyl, 3- [(N-ethyl-N-propylamino) methyl] cycloheptyl, 4- [2- (N -methyl-N- hexylamino) ethyl] cyclooctyl, 4-dimetilaminometilciclononilo, 2- (aminomethyl) cyclodecyl, 3- (2-aminomethyl) cycloundecyl, 2- (1-aminoethyl) cyclododecyl, 3- (3-aminopropyl) cyclotridecyl, 3- (4-aminobutyl ) cyclotetradecyl, 4- (5-arainopentil) cyclopentadecyl, 4- (6-aminohexyl) cyclohexadecyl, 2- (1, l-dimethyl-2-arainoetil) cyclononyl, 3- (2-methyl-3-aminopropyl) cyclodecyl, 3 - (methylaminomethyl) cycloundecyl, 2- (1-ethylaminoethyl) cyclododecyl, 2- (2-propylaminoethyl) cyclotridecyl, 3- (3-isopropylaminopropyl) cyclotetradecyl, 4- (4-butilaminobutil) cyclopentadecyl, 2- (5-pentilaminopentil) I cyclohexadecyl 2- (6-hexylaminohexyl) cyclononyl, 3- (dimethylaminomethyl) cyclododecyl, 3- [(N-ethyl-N-propylamino) methyl] cyclodecyl, 4- [2- (N-methyl-N-hexylamino) ethyl] cyclohexadecyl , 2, 2-dimethylcyclopropyl, and 2-trifluoromethylcyclopropyl. Examples of the lower alkenyl group include linear or branched alkenyl groups having 2 to 6 carbon atoms and 1 to 3 double bonds such as vinyl groups, 1-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-propenyl, 2-butenyl, 1-butenyl, 3-butenyl, 2-pentenyl, 1-pentenyl, 3-pentenyl, 4-pentenyl, 1,3-butadienyl, 1,3-pentadienyl, 2-penten-4- inyl, 2-hexenyl, 1-hexenyl, 5-hexenyl, 3-hexenyl, 4-hexenyl, 3, 3-dimethyl-1-propenyl, 2- ethyl-1-propenyl, 1, 3, 5-hexatrienyl, 1,3-hexadienyl, and 1,4-hexadienyl. Examples of the lower alkenyl group which may have a halogen atom as a substituent include, in addition to the lower alkenyl groups described above, linear or branched alkenyl groups having 2 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and which have 1 to 3 double bonds such as 3, 3, 3-trifluoro-1-propenyl, 2-bromovinyl, 3-chloro-1-propenyl, 3-iodo-1-methyl-1-propenyl groups, 3-fluoro-2-methyl-1-propenyl, 2-butenyl, 4, 4, 3-trichloro-1-butenyl, 4,4-difluoro-3-butenyl, 5-fluoro-2-pentenyl, 5, 5 3-tribromo-l-pentenyl, 5-chloro-3-pentenyl, 5,5,5-trifluoro-4-pentenyl, 4-chloro-l, 3-butadienyl, 5-fluoro-1,3-pentadienyl, 5- bromo-2-penten-4-ynyl, 6-fluoro-2-hexenyl, 6, 6, 5-trifluoro-1-hexenyl, 6-chloro-5-hexenyl, 5-bromo-3-hexenyl, 6-chloro- 4-Hexenyl, 3, 3-dimethyl-2-chloro-1-propenyl, 3-fluoro-2-ethyl-1-propenyl, 6-chloro-l, 3, 5-hexatrienyl, 6-bromo-1, 3- hexadienyl, and 6-fluoro -1, 4-hexadienyl. Examples of the benzoyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group which may have a halogen atom as a substituent and a halogen atom) include benzoyl groups ( which may have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 halogen atoms as substituents and a halogen atom) such as benzoyl, 3,4-difluorobenzoyl groups, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 4-ethoxybenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4- hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4- trifluoromethylbenzoyl, 2- (bromomethyl) benzoyl, 3- (2-chloroethyl) benzoyl, 4- (2,3-dichloropropyl) benzoyl, 4- (4-fluorobutyl) benzoyl, 3- (5-chloropentyl) benzoyl, 4- ( 5-bromohexyl) benzoyl, 4- (5,6-dibromohexyl) benzoyl, 3,4-di (trifluoromethyl) benzoyl, 3,4-di (4, 4, 4-trichlorobutyl) benzoyl, 2,4-di (3 -cloro-2-me tylpropyl) benzoyl, 2,5-di (3-chloropropyl) benzoyl, 2,6-di (2,2,2-trifluoroethyl) benzoyl, 3,4,5-tri (trifluoromethyl) benzoyl, 4- (2, 2 , 2-trichloroethyl) benzoyl, 2-methyl-1-trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-chloro-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-fluoro-4-trichloromethylbenzoyl, 2-methyl- 3-trifluoromethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4- bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2,4-diiodobenzoyl, 2,5-difluorobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3, 5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6- dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6,6-trifluorobenzoyl, and 2,4-difluorobenzoyl. Examples of the lower alkyl group substituted with halogen include linear or branched alkyl groups having 1 to 6 carbon atoms having 1 to 3 halogen atoms as substituents such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl groups , 2-chloroethyl, 2, 2, 2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro- 2-methylpropyl, 5-bromohexyl, and 5,6-dibromohexyl. Examples of the lower alkylenedioxy group include linear or branched alkylene groups having 1 to 4 carbon atoms such as methylenedioxy, ethylenedioxy, trimethylenedioxy, and tetramethylenedioxy groups. Examples of the amino group which may have a substituent selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a group benzoyl and a cycloalkyl group include amino groups which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkanoyl group having 1 to 6 carbon atoms, carbon, a benzoyl group, and a cycloalkyl group having 3 to 16 carbon atoms such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino , dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-RETYL-N-acetylamino, N-acetylamino, N-formylamino , N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, N-benzoylamino, N-ethyl-N-benzoylamino, N-methyl -N-benzoylamino, N-acetyl-N-benzoylamino, cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, cycloheptylamino, cyclooctylamino, N-methyl-N-cyclohexylamino, N-methyl-N-cyclopentylamino, N-methyl-N-cycloheptylamino, N-cyclohexyl-N-acetylaraine, N-cyclopentyl-N-benzoylaraine, cyclononylamino, cyclodecylamino, cyclododecylamino, cyclotridecylamino, cyclotetradecylamino, cyclopentadecylamino, N-methyl-N-cyclohexadecylamino, N-methyl-N-cyclononylamino, N-methyl-N-cyclodecylamino, N-cycloundecyl-N-acetylamino, and N- cyclohexadecyl-N-benzoyl. Examples of the lower alkanoyl group which may have a halogen atom as a substituent include, in addition to the lower alkanoyl described above, linear or branched alkanoyl groups having 2 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl groups, 3, 3,3-trifluoropropionyl, 3, 3, 3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6- bromohexanoyl, and 5,6-dibromohexanoyl. Examples of the lower alkoxycarbonyl group include alkoxycarbonyl groups having 1 to 6 carbon atoms such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, and hexyloxycarbonyl groups. Examples of the lower alkanoyloxy group include linear or branched alkanoyloxy groups having 2 to 6 carbon atoms such as acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butylcarbonyloxy, and hexanoyloxy groups.

Examples of the 5 or 6 membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyridyl groups, 1, 2, 5, 6 tetrahydropyridyl, thienyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, 2H-pyrrolyl, imidazolidinyl, pyrazolyl, imidazolyl, pyrazolidinyl, furazanyl, 2-imidazolinyl, imidazolidinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolidinyl, isooxazolyl, thiazolyl, isothiazolyl, pyranyl, 2-pyrazolidinyl, 1, 2,4-triazolyl, 1,2,3-triazolyl, 1, 2, 5-triazolyl, thiazolidinyl, 2-thiazolinyl, 1, 2, 3, 4-tetrazolyl, 1, 3, 4 oxadiazolyl, tetrahydropyranyl, and tetrahydrofuryl. Examples of the saturated 5- to 7-membered heterocyclic ring formed by joining R11 and R12 to each other, together with nitrogen atoms attached thereto, through or not through a nitrogen atom, a sulfur atom or an oxygen atom, include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups. Examples of the lower alkyl imidazolyl group include imidazolylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 4 or 5-) imidazolylmethyl groups, 2- [(1, 2, 4 or 5-) imidazolyl] ethyl, 1 - [(1, 2, 4 or 5) imidazolyl] ethyl, 3 - [(1, 2, 4 or 5) imidazolyl] propyl, 4 - [(1, 2, 4 or 5-) imidazolyl] butyl, 5 - [(1, 2, 4 or 5) imidazolyl] pentyl, 6 - [(1, 2, 4 or 5) imidazolyl] hexyl, 1,1-dimethyl -2- [(1, 2, 4 or 5-) imidazolyl] ethyl, and 2-methyl-3- [(1, 2, 4 or 5) imidazolyl] propyl. Examples of the 1,2,4-triazolyl lower alkyl group include 1,2-triazolylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups (1, 3 or 5) , 2, 4-triazolylmethyl, 2 - [(1, 3 or 5) l, 2,4-triazolyl] ethyl, 1 - [(1, 3 or 5) l, 2,4-triazolyl] ethyl, 3 - [(1, 3 or 5-) 1, 2, 4-triazolyl] propyl, 4 - [(1, 3 or 5-) 1,2, -triazolyl] butyl, 5 - [(1, 3 or 5- ) l, 2,4-triazolyl] pentyl, 6 - [(1, 3 or 5-) 1, 2, 4-triazolyl] hexyl, 1,1-dimethyl-2- [(1, 3 or 5) 1 , 2,4-triazolyl] ethyl, and 2-methyl-3- [(1, 3 or 5-) 1, 2,4-triazolyl] propyl. Examples of the 1,2,3-triazolyl lower alkyl group include 1,2,3-triazolylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups (1, 4 or 5) 1, 2, 3-triazolylmethyl, 2 - [(1, 4 or 5-) 1,2,3-triazolyl] ethyl, 1 - [(1, 4 or 5) l, 2,3-triazolyl] ethyl, 3 - [(1, 4 or 5-) 1, 2, 3-triazolyl] propyl, 4 - [(1, 4 or 5-) l, 2,3-triazolyl] butyl, 5 - [(1, 4 or 5-) l, 2,3-triazolyl] pentyl, 6 - [(1, 4 or 5) 1, 2 , 3-triazolyl] hexyl, 1,1-dimethyl-2- [(1, 4 or 5-) 1, 2, 3-triazolyl] ethyl, and 2-methyl-3- [(1, 4 or 5-) 1, 2, 3-triazolyl] propyl. Examples of the 1, 2, 5-triazolyl lower alkyl group include 1, 2, 5-triazolylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 3 or 4) 1, 2, 5-triazolylmethyl, 2 - [( 1, 3 or 4) l, 2,5-triazolyl] ethyl, 1 - [(1, 3 or 4-) l, 2,5-triazolyl] ethyl, 3 - [(1, 3 or 4) 1 , 2, 5-triazolyl] propyl, 4 - [(1, 3 or 4-) 1,2, 5-triazolyl] butyl, 5 - [(1, 3 or 4-) l, 2,5-triazolyl] pentyl , 6 - [(1, 3 or 4-) 1, 2, 5-triazolyl] hexyl, 1,1-dimethyl-2- [(1, 3 or 4-) 1, 2, 5-triazolyl] ethyl, and 2-methyl-3- [(1, 3 or 4-) 1, 2, 5-triazolyl] propyl. Examples of the pyrazolyl lower alkyl group include pyrazolylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 3, 4 or 5) pyrazolylmethyl groups, 2 - [(1, 3, 4 or 5-) pyrazolyl] ethyl, 1 - [(1, 3, 4 or 5) pyrazolyl] ethyl, 3 - [(1, 3, 4 or 5) pyrazolyl] propyl, 4 - [(1, 3 , 4 or 5-) pyrazolyl] butyl, 5 - [(1, 3, 4 or 5) pyrazolyl] pentyl, 6 - [(1, 3, 4 or 5) pyrazolyl] hexyl, 1, 1-dimethyl- 2- [(1, 3, 4 or 5-) pyrazolyl] ethyl, and 2-methyl-3- [(1, 3, 4 or 5) pyrazolyl] propyl. Examples of the pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring include pyrimidinylalkyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring and whose alkyl portion is a linear alkyl group or branched that has 1 to 6 carbon atoms such as (2, 4, 5 or 6-) pyrimidinylmethyl, 2- [(2, 4, 5 or 6-) pyrimidinyl] ethyl, l - [(2, 4, 5 or 6-) pyrimidinyl] ethyl, 3 groups - [(2, 4, 5 or 6-) pyrimidinyl] propyl, 4 - [(2, 4, 5 or 6-) pyrimidinyl] butyl, 5 - [(2, 4, 5 or 6-) pyrimidinyl] pentyl, 6 - [(2, 4, 5 or 6-) pyrimidinyl] hexyl, 1, l-dimethyl-2- [(2, 4, 5 or 6-) pyrimidinyl] ethyl, 2-methyl-3- [(2, 4, 5 or 6-) pyrimidinyl] propyl, [(1, 3, 4 or 5-) 2,6-dioxopyrimidinyl] methyl, [(1, 3, 4, 5 or 6-) 2-oxopyrimidinyl] methyl, [ (1, 2, 4 or 5-) 6-oxopyrimidinyl] methyl, [(1, 2, 5 or 6-) 4-oxopyrimidinyl] methyl, [(1, 3, 5 or 6-) 2,4-dioxopyrimidinyl] methyl, 2- [(4 or 6-) 2,5-dioxopyrimidinyl] ethyl, 1 - [(1, 3, 4 or 5-) 2,6-dioxopyrimidinyl] ethyl, 3 - [(1, 3 or 5) -) 2,4,6-trioxopyrimidinyl] propyl, 4 - [(1, 3, 4 or 5) 2,6-dioxopyrimidinyl] butyl, 5- [(4 or 6-) 2,5-dioxopyrimidinyl] pentyl, 6 - [(1, 3, 5 or 6-) 2,4-dioxopyrimidinyl] hexyl, 1, 1-dimethyl- [(1, 3 3, 4 or 5) 2,6-dioxopyrimidinyl] ethyl, and -methyl-3- [(1, 3 3, 4 or 5-) 2,6-dioxopyrimidinyl] propyl. Examples of the 3, 5-dioxoisoxazolidin-4-ylidene lower alkyl group include 3,5-dioxoisoxazolidin-4-ylidenealkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups 3, 5 dioxoisoxazolidin-4-ylidenemethyl, 3,5-dioxoisoxazolidin-4-ylidenethyl, 3,5-dioxoisoxazolidin-4-ylidenepropyl, 3,5- dioxoisoxazolidin-4-ylideneisopropyl, 3,5-dioxoisoxazolidin-4-ylidenebutyl, 3,5-dioxoisoxazolidin-4-ylidenepentyl, and 3,5-dioxoisoxazolidin-4-ylidenehexyl. Examples of the 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring include 1,2,4-oxadiazolylalkyl groups which may have a linear or branched having 1 to 6 carbon atoms as a substituent on the 1,2,4-oxadiazole ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups (3 or 5) 1,2,4-oxadiazolylmethyl, 2 - [(3 or 5-) 1, 2,4-oxadiazolyl] ethyl, l - [(3 or 5-) l, 2,4-oxadiazolyl] ethyl, 3 - [( 3 or 5-) l, 2,4-oxadiazolyl] propyl, 4 - [(3 or 5-) 1, 2,4-oxadiazolyl] butyl, 5 - [(3 or 5-) 1,2,4-oxadiazolyl ] pentyl, 6 - [(3 or 5-) l, 2,4-oxadiazolyl] hexyl, 1, l-dimethyl-2- [(3 or 5-) l, 2,4-oxadiazolyl] ethyl, 2-methyl -3- [(3 or 5-) 1, 2,4-oxadiazolyl] propyl, 5-methyl-3- (1, 2, 4-oxadiazolyl) methyl, 3-ethyl-2- [5- (1, 2 , 4-oxadiazolyl)] ethyl, 1- [3-propyl-5- (1,2,4-oxadiazolyl)] ethyl, 3- [5-buty1-3- (1,2, 4-oxadi azolyl)] propyl, 4- [3-penti1-5- (1,2,4-oxadiazolyl)] butyl, 5- [5-hexyl-3- (1,2,4-oxadiazolyl)] pentyl, 6- [ 3-methy1-5- (1,2,4-oxadiazolyl)] hexyl, 1, l-dimethyl-2- [5-isopropyl-3- (1, 2,4-oxadiazolyl)] ethyl, and 2-methyl- 3- [3-isobutyl-5- (1,2,4-oxadiazolyl)] propyl. Examples of the thiazolidinyl lower alkyl group which may have an oxo-corao group or a substituent on the thiazolidine ring include thiazolidinyl-alkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 atoms carbon such as (2, 3, 4 or 5) thiazolidinylmethyl, 2- [(2, 3, 4 or 5-) thiazolidinyl] ethyl, l - [(2, 3, 4 or 5) thiazolidinyl] ethyl groups , 3 - [(2, 3, 4 or 5-) thiazolidinyl] propyl, 4 - [(2, 3, 4 or 5) thiazolidinyl] butyl, 5 - [(2, 3, 4 or 5) thiazolidinyl] pentyl, 6 - [(2, 3, 4 or 5-) thiazolidinyl] hexyl, 1, l-dimethyl-2- [(2, 3, 4 or 5-) thiazolidinyl] ethyl, 2-methyl-3- [( 2, 3, 4 or 5) thiazolidinyl] propyl, 2,4-dioxo-5-thiazolidinylmethyl, 2- [2-oxo- (3, 4 or 5) thiazolidinyl] ethyl, 1- [4-oxo- ( 2, 3 or 5) thiazolidinyl] ethyl, 3- [5-oxo- (2, 3 or 4) thiazolidinyl] propyl, 4- [2, 5-dioxo- (3 or 4) thiazolidinyl] butyl, - [2, 4, 5-trioxo-3-thiazolidinyl] pentyl, 6- [4,5-dioxo- (2 or 3- ) thiazolidinyl] hexyl, 1, l-dimethyl-2- [2, 4-dioxo- (3 or 5) thiazolidinyl] ethyl, 2-methyl-3- [2,4-dioxo- (3 or 5) thiazolidinyl) ] propyl, and 3- [2, 4-dioxo- (3 or 5) thiazolidinyl] propyl. Examples of the phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include, in addition to the phenyl lower alkyl groups described above, phenylalkyl groups which may have a linear alkylenedioxy group or branched alkyl having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups 3, 4-methylenedioxybenzyl, 3,4- trimetilendioxibencilo, 2- (2, 3-ethylenedioxyphenyl) ethyl, l- (3,4-trimetilendioxifenil) ethyl, 3- (2, 3-tetrametilendioxifenil) propyl, 4- (3, 4-methylenedioxyphenyl) butyl, 5- (2, 3 ethylenedioxyphenyl) pentyl, 6- (3, 4-trimethylenedioxyphenyl) hexyl, 1, l-dimethyl-2- (2,3-methylenedioxyphenyl) ethyl, and 2-methyl-3- (3,4-ethylenedioxyphenyl) propyl. Examples of the lower alkoxycarbonyl lower alkyl group include alkoxycarbonylalkyl groups whose alkoxy part is an alkoxy straight or branched group having 1 to 6 carbon atoms and alkyl portion is a linear or branched alkyl having 1 to 6 carbon atoms such as groups methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-methoxycarbonylethyl, 2-ethoxycarbonylethyl, 1-ethoxycarbonylethyl, 3-methoxycarbonylpropyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxicarbonilpentilo, 6-propoxicarbonilhexilo, 1,1-dimeti1-2-butoxycarbonylethyl, 2-methyl- 3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, and hexyloxycarbonylmethyl. Examples of the carboxyl lower alkyl group include carboxyalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl groups, , l-dimethyl-2-carboxyethyl, and 2-methyl-3-carboxypropyl. Examples of the lower alkanoyl group substituted with morpholino include alkanoyl groups substituted with morpholino whose alkanoyl portion is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2 - [(2, 3 or 4) morpholino] acetyl groups, 3 - [(2, 3 or 4-) morpholino] propionyl, 2 - [(2, 3 or 4) morpholino] propionyl, 4- [(2, 3 or 4-) morpholino] butyryl, 5 - [(2) , 3 or 4) morpholino] pentanoyl, 6 - [(2, 3 or 4) morpholino] hexanoyl, 2,2-dimethyl-2- [(2, 3 or 4-) morpholino] propionyl, and 2-methyl -3- [(2, 3 or 4-) morpholino] propionyl. Examples of the piperazinylcarbonyl lower alkyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylcarbonylalkyl groups whose alkyl portion is a linear or branched alkyl group which has 1 to 6 carbon atoms and which can be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which can have a straight or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl group and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-) piperazinyl carbonylmethyl groups, 2 - [(1) , 2 3-) piperazinyl carbonylethyl, 1 - [(1, 2 or 3) piperazinyl carbonylethyl, 3 - [(1, 2 or 3) piperazinylcarbonylpropyl, 4 - [(1, 2 or 3) piperazinylcarbonylbutyl, 5 - [(1, 2 or 3-) piperazinylcarbonylpentyl, 6 - [(1, 2 or 3-) piperazinylcarbonylhexyl, 1, l-dimethyl-2- [(1,2-) piperazinylcarbonylethyl, 2-methyl -3- [(1,2-) piperazinylcarbonylpropyl, (4-benzyl-l-piperazinylcarbonyl) methyl, 2- [4- (2-phenylethyl) -l-piperazinylcarbonyl] ethyl, 1- [4- (3- phenylpropyl) -1-piperazinylcarbonyl] ethyl, 3- [4- (4-phenylbutyl) -1-piperazinylcarbonyl] propyl, 4- [4- (5-phenylpentyl) -1-piperazinylcarbonyl] butyl, 5- [4- (6 phenylpropyl) -1-piperazinylcarbonyl] pentyl, 6- (4-benzyl-l-piperazinylcarbonyl) hexyl, 1, l-dimethyl-2- (4-benzyl-l-piperazinylcarbon il) ethyl, 2-methyl-3- (4-benzyl-l-piperazinylcarbonyl) propyl, [4- (3, -raethylenedioxybenzyl) -1-piperazinylcarbonyl] methyl, 2-. { 4- [2- (2,3-ethylenedioxyphenyl) ethyl] -1-piperazinylcarbonyl} ethyl, 1-. { 4- [3- (3, 4-trimethylenedioxyphenyl) propyl] -1-piperazinylcarbonyl} ethyl, 3-. { 4- [4- (2,3-tetramethylenedioxyphenyl) butyl] -l- piperaziniIcarbonil} propyl, 4-. { 4- [5- (3,4-methylenedioxyphenyl) pentyl] -1-piperazinylcarbonyl} butyl, 5-. { 4- [3- (2, 3-ethylenedioxyphenyl) propyl] -1-piperazinylcarbonyl} pentyl, 6- [4- (3, 4-trimethylenedioxybenzyl) -1-piperazinylcarbonyl] hexyl, 1, l-dimethyl-2- [4- (2,3-tetramethylenedioxybenzyl) -1-piperazinylcarbonyl] ethyl, 2-methyl- 3- [4- (3, 4-Rethylenedioxybenzyl) -1-piperazinylcarbonyl] propyl, (3,4-dibenzyl-l-piperazinylcarbonyl) methyl, (3,, 5-tribenzyl-1-piperazinylcarbonyl) methyl, [2, 4 -di (3,4-methylenedioxybenzyl) -1-piperazinylcarbonyl] methyl, [2,, 6-tri (3,4-methylenedioxybenzyl) -1-piperazinylcarbonyl] methyl, and [3-benzyl-4- (3, 4- methylenedioxybenzyl) -1-piperazinylcarbonyl] methyl. Examples of the piperazinyl lower alkanoyl group which can be substituted on the piperazine ring with a phenyl lower alkyl group which can have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalloyl groups whose alkanoyl portion is a linear or branched alkanoyl group which has 2 to 6 carbon atoms and may be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which may have a straight or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose Alkyl is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 2 - [(1, 2 or 3) piperazinyl] acetyl groups, 3 - [(1, 2 or 3) ) piperazinyl] propionyl, 2 - [(1, 2 or 3) piperazinyl] propionyl, 4 - [(1, 2 or 3) piperazinyl] butyryl, 5 - [(1, 2 or 3) piperazinyl] pentanoyl, 6 - [(1, 2 or 3-) piperazinyl] hexanoyl, 2, 2-dimethyl-3- [(1, 2 or 3) piperazinyl] propionyl, 2-methyl-3 - [(1, 2 or 3- ) piperazinyl] propionyl, 2- (4-benzyl-l-piperazinyl) acetyl, 3- [4- (2-phenylethyl) -l-piperazinyl] propionyl, 2- [4- (3-phenylpropyl) -1-piperazinyl] propionyl, 4- [4- (4-phenylbutyl) -l-piperazinyl] butyryl, 5- [4- (5-phenylpentyl) -l-piperazinyl] pentanoyl, 6- [4- (6-phenylpropyl) -1-piperazinyl ] hexanoyl, 6- (4-benzyl-l-piperazinyl) hexanoyl, 2, 2-dimethy1-3- (4-benzyl-l-piperazinyl) propionyl, 2-methyl-3- (4-benzyl-l-piperazinyl) propionyl, 2- [4- (3, -methylenedioxybenzyl) -l- piperazinyl] acetyl, 3-. { 4- [2- (2,3-ethylenedioxyphenyl) ethyl] -1-piperazinyl} propionyl, 2-. { 4- [3- (3, 4-triraethylenedioxyphenyl) propyl] -1-piperazinyl} propionyl, 4-. { 4- [4- (2,3-tetramethylenediphenyl) butyl] -1-piperazinyl} butyryl, 5-. { 4- [5- (3, 4-methylenedioxyphenyl) pentyl] -l-piperazinyl} pentanoyl, 5-. { 4- [3- (2,3-ethylenedioxyphenyl) propyl] -1-piperazinyl} pentanoyl, 6- [4- (3, 4 -trimetilendioxibencil) -1-piperazinyl] hexanoyl, 2, 2-dimethyl-3- [4- (2, 3-tetrametilendioxibencil) -1-piperazinyl] propionyl, 2-methyl- 3- [4- (3, -methylenedioxybenzyl) -1-piperazinyl] propionyl, 2- (3,4-dibenzyl-1-piperazinyl) acetyl, 2- (3,4,5-tribenzyl-1-piperazinyl) acetyl, 2- [2, -di (3, -raethylenedioxybenzyl) -1- piperazinyl] acetyl, 2- [2,4-, 6-tri (3, -methylenedioxybenzyl) -1-piperazinyl] acetyl, and 2- [3-benzyl-4- (3, -methylenedioxybenzyl) -1-piperazinyl] acetyl. Examples of the lower alkyl group substituted with morpholinocarbonyl include morpholinocarbonylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 3 or 4-) morpholino] carbonylmethyl groups, 2- [(2) , 3 or 4) morpholino] carbonylethyl, l- [(2, 3 or 4) morpholino] carbonylethyl, 3- [(2, 3 or 4) raorfolino] carbonylpropyl, 4- [(2, 3 or 4- ) morpholino] carbonyl butyl, 5- [(2, 3 or 4-) morpholino] carbonylpentyl, 6- [(2, 3 or 4) morpholino] carbonylhexyl, 1, 1-dimethyl -2- [(2, 3 or 4-) morpholino] carbonylethyl, and 2-methyl- -3- [(2, 3 or 4) morpholino] carbonylpropyl. Examples of the imidazolyl lower alkanoyl group include imidazolylalkanoyl groups whose alkanoyl portion is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2 - [(1, 2, 4 or 5) imidazolyl] acetyl groups, 3- [ (1, 2, 4 or 5) imidazolyl] propionyl, 2 - [(1, 2, 4 or 5) imidazolyl] propionyl, 4 - [(1, 2, 4 or 5) imidazolyl] butyryl, 5- [(1, 2, 4 or 5-) imidazolyl] pentanoyl, 6 - [(1, 2, 4 or 5) imidazolyl] hexanoyl, 2, 2-dimethyl-3- [(1, 2, 4 or 5- ) imidazolyl] propionyl, and 2-methyl-3- [(1, 2, 4 or 5- [39 ) imidazolyl] propionyl. Examples of the cycloalkylcarbonyl group include cycloalkylcarbonyl groups whose cycloalkyl moiety is a cycloalkyl group having 3 to 16 carbon atoms such as cyclopropylcarbonyl group, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, ciclooctilcarbonilo, ciclononilcarbonilo, ciclodecilcarbonilo, cicloundecilcarbonilo, ciclododecilcarbonilo, ciclotridecilcarbonilo, ciclotetradecilcarbonilo I ciclopentadecilcarbonilo , and cyclohexadecylcarbonyl. Examples of the lower alkanoyl group substituted with amino which may have a lower alkyl group as a substituent include linear or branched alkanoyl groups having 2 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups They are having 1 to 6 carbon atoms as substituents such as aminoacetyl, 2-aminopropionyl, 3-aminopropionyl, 4-aminobutyryl, 5-aminopentanoilo, 6-arainohexanoilo, 2, 2-dimethyl-3-aminopropionyl, 2-methyl-3 -arainopropionilo, methylaminoacetyl, 2-etilaminopropionilo, 3-propilaminopropionilo, 3-isopropilaminopropionilo, 4-butilaminobutirilo, 5-pentilaminopentanoilo, 6-hexilaminohexanoilo, dimethylaminoacetyl, 3-diisopropilaminopropionilo, (N-ethyl-N- propylamino) acetyl, and 2- (N-methyl-N-hexylamino) acetyl. Examples of the lower alkylene group which may have a hydroxyl group as a substituent include, in addition to the lower alkylene groups described above, linear or branched alkylene groups having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents such as 1-hydroxymethylene, 2-hydroxyethylene, 1-hydroxyethylene, 2-hydroxytrimethylene, 3-hydroxytrimethylene, 1-hydroxytrimethylene, 3-hydroxy-2-methyltrimethylene, l-hydroxy-2-methyltrimethylene, 3-hydroxy-2, 2 groups. dimethyltrimethylene, 1-hydroxy-2,2-dimethyltrimethylene, 3-hydroxy-1-methyltrimethylene, 2-hydroxy-1-methyltrimethylene, 1-hydroxymethylmethylene, hydroxymethylmethylene, 2-hydroxymethyltrimethylene, 2-hydroxymethyl-2-methyltrimethylene, (2- hydroxyethyl) methylene, (1-hydroxyethyl) methylene, 4-hydroxytetramethylene, 2-hydroxytetramethylene, 3-hydroxytetramethylene, 1-hydroxytetramethylene, 5-hydroxypentamethylene, 4-hydroxypentamethylene, 3-hydroxypentamethylene, 2-hydroxypentamethylene or, 1-hydroxypentamethylene, 6-hydroxyhexamethylene, 5-hydroxyhexamethylene, 4-hydroxyhexamethylene, 3-hydroxyhexamethylene, 2-hydroxyhexamethylene, 1-hydroxyhexamethylene, 1,2-dihydroxytrimethylene, 2, 2, -trihydroxytetramethylene, 1,2,6-trihydroxyhexamethylene , and 3, 4, 5-trihydroxypentamethylene.

Examples of the alkyl group which may have a hydroxyl group as a substituent include, in addition to the lower alkyl groups described above, linear or branched alkyl groups having 1 to 16 carbon atoms which may have 1 to 3 hydroxyl groups as substituents as heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, 1-methylhexyl, hexadecyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5, 5, 4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl. Examples of the alkyl group substituted with hydroxyl group include linear or branched alkyl groups having 1 to 16 carbon atoms and 1 to 3 hydroxyl groups as substituents such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2 groups, 3-dihydroxypropyl, 4-hydroxybutyl, 1, l-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl. Examples of the cycloalkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a lower alkyl group include, in addition to the cycloalkyl groups described above, cycloalkyl groups having 3 to 16 carbon atoms which they may have 1 to 3 substituents selected from the group consisting of a hydroxyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-hydroxycyclopropyl, 3-hydroxycyclobutyl, 3-hydroxycyclopentyl, 2-hydroxycyclohexyl, -hydroxycyclohexyl, 3-hydroxycycloheptyl, 4-hydroxycyclooctyl, 5-hydroxy cyclononyl, 3-hydroxycyclodecyl, 4-hydroxycycloundecyl, 5-hydroxycyclododecyl, 6-hydroxycyclotridecyl, 7-hydroxycyclo tetradecyl, 6-hydroxycyclopentadecyl, 8-hydroxycyclohexadecyl, 2,4-dihydroxycyclohexyl, , 4,6-trihydroxycyclohexyl, 1-methylcyclopentyl, 2-ethylcyclopropyl, 3-n-propylcyclobutyl, 2-n-butylcyclohexyl, 4-n-pentylcycloheptyl, 4-n-hexylcyclooctyl, 2,3-dimethylcyclohexyl, 2, 3, 4 -trimethylcyclohexyl, and 2-methyl-4-hydroxycyclohexyl. Examples of the phenoxy lower alkyl group include phenoxyalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as phenoxymethyl, 2-phenoxyethyl, 1-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 1 groups, l-dimethyl-2-phenoxyethyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1-phenoxyisopropyl, and 2-methyl-3-phenoxypropyl. Examples of the lower alkoxy amino group which may have a lower alkyl group as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethoxy, 2-aminoethoxy, 1- groups aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1, l-dimethyl-2-arainoetoxi, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexilaminohexiloxi, dimethylaminomethoxy, 2-diethylaminoethoxy, 2-diisopropylaminoethoxy, (N-ethyl-N-propylamino) methoxy, and 2- (N-meti1-N-hexylamino) ethoxy. Examples of the lower alkyl group substituted with a hydroxyl group include linear or branched alkyl groups having 1 to 6 carbon atoms having 1 to 3 hydroxyl groups corao substituents such as hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 3-hydroxypropyl groups, 2, 3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5, 5, -trihidroxipentilo, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl. Examples of the amino group which may have a lower alkylsulfonyl group as a substituent include amino groups which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents such as, N-ethylsulfonyl-N- amino, methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, tert-butylsulfonylamino, pentylsulfonylamino, hexylsulfonylamino, dimetilsulfonilamino, dietilsulfonilamino, dipropilsulfonilamino, dibutilsulfonilamino, dipentilsulfonilamino, dihexilsulfonilamino,-methylsulfonyl-N-ethylsulfonylamino N propylsulfonylamino, N-methylsulfonyl-N-butylsulfonylamino, and N-methylsulfonyl-N-hexylsulfonylamino. Examples of the lower alkynyl group include linear or branched alkynyl groups having 2 to 6 carbon atoms such as ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl, 2-pentynyl, and -hexinyl. Examples of the anilino group which may have a halogen atom as a substituent on the phenyl ring include anilino groups which may have 1 to 3 halogen atoms as substituents on the phenyl ring such as fluoroanilino 3-anilino, 2-fluoroanilino, , 4-fluoroanilino, 2-broraoanilino, 3-bromoanilino, 4-bromoanilino, 2-iodoanilino, 3-iodoanilino, 4-iodoanilino, 2,3-dibroraoanilino, 2, 4-diyodoanilino, 2, 5-difluoroanilino, 2,6 -dichloroanilino, 2,4,6-trichloroanilino, 2,6-difluoroanilino, 3,5-difluoroanilino, 2,6-difluoroanilino, 2-chloroanilino, 3- chloroanilino, 4-chloroanilino, 2, 3-dichloroanilino, 2,4-dichloroanilino, 2, 5-dichloroanilino, 3, -dicloroanilino, 2,6-dichloroanilino, 3, 5-dichloroanilino, 2, 4, 6-trifluoroanilino, 2 , 4-difluoroanilino, and 3,4-difluoroanilino. Examples of the piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring include piperazinyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring such as (1-, 2- or 3-) piperazinyl, 4-methyl- (l-, 2- or 3-) piperazinyl, 2,3-dimethyl- (1- or 5-) piperazinyl groups, and 2, 3 , 4-trimethyl- (1-, 5- or 6-) piperazinyl. Examples of the pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring include pyrrolidinyl groups which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring such as groups (1-, 2- or 3-) ) pyrrolidinyl, 2-oxo- (l-, 3-, 4- or 5-) pyrrolidinyl, 3-oxo- (l-, 2-, 4- or 5-) pyrrolidinyl, 2,3-dioxo- (1- , 4- or 5-) pyrrolidinyl, and 2,5-dioxo- (l-, 3- or 4-) pyrrolidinyl. Examples of the lower alkanoyl amino group include linear or branched alkanoyl amino groups having 2 to 6 carbon atoms having 1 to 3 halogen atoms as substituents such as acetyl amino, propionyl amino, butyryl amino, pentanoyl amino, 2-methylpropionyl amino groups , e hexanoyl amino. Examples of the phenyl group which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; a lower alkoxy amino group which may have a lower alkyl group as a substituent; a lower alkyl group substituted with hydroxyl; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a lower alkanoylamino group; a cyano group; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; and a phenoxy group include phenyl groups which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms; a halogen atom; an group aminoalkoxy whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms and which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents; a linear or branched alkyl group having 1 to 6 carbon atoms and 1 to 3 hydroxyl groups as substituents; a phenylalkyl group whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkynyl group having 2 to 6 carbon atoms; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a linear or branched alkylthio group having 1 to 6 carbon atoms; a cycloalkyl group having 3 to 16 carbon atoms; a phenylthio group; an adamantyl group; an anilino group which may have 1 to 3 halogen atoms as substituents on the phenyl ring; a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms; an amino group which may have 1 or 2 linear or branched alkanoyl groups having 2 to 6 carbon atoms; a cyano group; a piperazinyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring; a pyrrolidinyl group which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring; and a phenoxy group such as phenyl groups, 2-methylphenyl, 3- methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-isopropylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3-dimethylphenyl, 3-diethylphenyl, 2, -dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl , 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2, -dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2- (bromomethoxy) phenyl, 3- (2-chloroethoxy) phenyl, 4- (2,3-dichloropropoxy) phenyl, 4- (4-fluorobutoxy) phenyl, 3- (5-chloropentyloxy) phenyl, 4- (5-bromohexyloxy) phenyl, 4- (5,6-dibromohexyloxy) phenyl, 3,4-di (trifluoromethoxy) phenyl, 3,4-di (4, 4, 4-trichlorobutoxy) ) phenyl, 2,4-di (3-chloro-2-methoxypropyl) phenyl, 2,5-di (3-chloropropoxy) phenyl lo, 2,6-di (2,2,2-trifluoroethoxy) phenyl, 3,4,5-tri (trifluoromethoxy) phenyl, 4- (2,2,2-trichloroethoxy) phenyl, 2-methyl-4-trifluoromethoxyphenyl , 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-methyl-3-trifluorornetoxy-4-trifluoromethoxyphenyl, 2-phenoxyphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl, , 3-diphenoxyphenyl, 3,4-diphenoxyphenyl, 2,6-diphenoxyphenyl, 3,4,5-trifenoxyphenyl, 2-methyl-4-phenoxyphenyl, 3-ethyl-4-phenoxyphenyl, 2-methoxy-4-phenoxyphenyl, 3-ethoxy-4-phenoxyphenyl, 2-methyl-3-phenoxy-4-trifluoromethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2, 3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3, -difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,, 6-trifluorophenyl, 2-bromophenyl, 3-bromophenyl, 4- bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 4-methylthiophenyl, 4-cyclohexylphenyl, 4-chloro-2-anilinophenyl, 2- (4-chloroaniline) -5-ethoxycarbonylphenyl, 4- [2- (N, N-diethylamino) ethoxy] phenyl, 4- (4-methyl-l-piperazinyl) phenyl, 4- (2-oxo-l-pyrrolidinyl) phenyl, 4- Methylsulfonylaminophenyl, 4- (2-hydroxyethyl) phenyl, 4-benzylphenyl, 4-ethynylphenyl, 4-phenylthiophenyl, 4- (1-adamantyl) phenyl, 5-acetylamino-2-chlorophenyl, 2-propanoylamino enyl, 3-cyanophenyl, 2-cyanophenyl, 4-cyanophenyl, 3-dicyanophenyl, and 3,4,5-tricyclophenyl. Examples of the phenyl lower alkyl group which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and an alkyl group lower include, in addition to the phenyl lower alkyl groups described above, phenylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms and which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a group linear or branched alkoxy having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkyl group having 1 to 6 carbon atoms such as 4-fluorobenzyl, 2-chlorobenzyl groups , 3-chlorobenzyl, 4-chlorobenzyl, 2- (2-fluorophenyl) ethyl, 2- (4-fluorophenyl) ethyl, 2- (4-chlorophenyl) ethyl, 3,4-dibromobenzyl, 3,4-diiodobenzyl, 2, 4-difluorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4,5-trifluorobenzyl, 3- (4-chlorophenyl) propyl, 1- (2-bromophenyl) ethyl, 4- (3-fluorophenyl) butyl , 5- (4-iodophenyl) pentyl, 6- (4-chlorophenyl) hexyl, 1, l-dimethyl-2- (3-fluorophenyl) ethyl, 2-methyl-3- (4-chlorophenyl) propyl, 2-methylbenzyl , 2- (3-methylphenyl) ethyl, 3- (4-methylphenyl) propyl, 1- (2-ethylphenyl) ethyl, 4- (3-ethylphenyl) butyl, 5- (4-ethylphenyl) pentyl, 6- (4- isopropylphenyl) hexyl, 1, l-dimethyl-2- (3-butylphenyl) ethyl, 2-methyl-3- (4-pentylphenyl) propyl, 4-hexylbenzyl, 3,4-dimethylbenzyl, 3,4-diethylbenzyl, 2, 4-dimethylbenzyl, 2,5-dimethylbenzyl, 2,6-diraethylbenzyl, 3,4,5-triraethylbenzyl, 2-methoxybenzyl, 2- (2-methoxyphenyl) ethyl, 2- (3-ethoxyphenyl) ethyl, 2- (4 -methoxyphenyl) ethyl, 4-methoxybenzyl, 1- (2-ethoxyphenyl) ethyl, 3- (3-ethoxyphenyl) propyl, 4- (4-ethoxyphenyl) butyl, 5- (4-isopropoxyphenyl) pentyl, 6- (3-butoxyphenyl) hexyl, 1, 1-dimethyl -2- (4-pentyloxyphenyl) ethyl, 2-methyl-3- (4-hexyloxyphenyl) propyl, 3, -dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, 2,6- dimethoxybenzyl, 3,4,5-trimethoxybenzyl, 2-trifluoromethoxybenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2- [2- (bromomethoxy) phenyl] ethyl, 1- [3- (2-chloroethoxy) phenyl] ethyl, 3- [4- (2,3-dichloropropoxy) phenyl] propyl, 4- [4- (4-fluorobutoxy) phenyl] butyl, 5- [3- (5-chloropentyloxy) phenyl] pentyl, 6- [4- (5- bromohexyloxy) phenyl] hexyl, 1, l-dimethyl-2- [4- (5,6-dibromohexyloxy) phenyl] ethyl, 3,4-di (trifluororatoethoxy) benzyl, 3,4-di (4, 4, 4- trichlorobutoxy) benzyl, 2,4-di (3-chloro-2-ethoxypropyl) encyl, 2,5-di (3-chloropropoxy) benzyl, 2,6-di (2,2,2-trifluoroethoxy) benzyl, 3, 4,5-tri (trifluoromethoxy) benzyl, 4- (2,2,2-trichloroethoxy) benzyl, 2-methyl -4-trifluoromethoxybenzyl, 3-ethyl-4-trichloromethoxybenzyl, 2-methoxy-4-trifluoromethoxybenzyl, 3-ethoxy-4-trichloromethoxybenzyl, 2-methyl-3-trifluoromethoxy-4-trifluoromethoxybenzyl, 2-chloro-3-methylbenzyl, -fluoro-2-trifluoro-ethoxybenzyl, and 3-chloro-2-ethyl-4-methoxybenzyl. Examples of the phenyl lower alkyl group having a lower alkylenedioxy group as a substituent on the Phenyl ring include phenylalkyl groups having a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and which alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2- (2, 3-ethylenedioxyphenyl) ethyl, 1- (3,4-trimethylenedioxyphenyl) ethyl, 3- (2,3-tetramethylenedioxyphenyl) propyl, 4- (3, 4-methylenedioxyphenyl) butyl, 5- (2,3-ethylenedioxyphenyl) pentyl, 6- (3,4-trimethylenedioxyphenyl) hexyl, 1,1-dimethyl-2- (2,3-methylenedioxyphenyl) ethyl, and 2-methyl- 3- (3, 4-ethylenedioxyphenyl) propyl. Examples of the amino group which may have a lower alkanoyl group as a substituent include amino groups which may have a linear or branched alkanoyl group having 1 to 6 carbon atoms as a substituent such as amino, N-acetylamino, N-formylamino groups , N-propionylamino, N-butyrylaraine, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, and N-hexanoylamino. Examples of the group 1, 2, 3, -tetrahydroquinolyl which may have, in the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group include groups 1, 2, 3, 4-tetrahydroquinolyl which may have, in the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a linear or branched alkoxy group having 1 to 6 carbon atoms, and a straight or branched alkylenedioxy group having 1 to 4 carbon atoms such as groups (1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl, 2-oxo- (1, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4 -tetrahydroquinolyl, 2-oxo-6,7-methylenedioxy- (1, 3, 4, 5 or 8-) 1, 2, 3, 4-tetrahydroquinolyl, 4-oxo- (1, 2, 3, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl, 2,4-dioxo- (1, 3, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl, 2,4-dioxo -6,7-methylenedioxy- (1, 3, 5 or 8-) 1,2, 3,4-tetrahydroquinolyl, 5,6-ethylenedioxy- (1, 2, 3, 4, 7 or 8-) 1, 2 , 3, 4-tetrahydroquinolyl, 7, 8-trimethylenedioxy- (1, 2, 3, 4, 5 or 6-) 1, 2, 3, 4-tetrahydroquinolyl, 6,7-tetramethylenedioxy- (1, 2, 3, 4, 5 or 8-) 1, 2, 3, 4-tetrahydroquinolyl, 5-methoxy-2-oxo- (1, 3, 4, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl, and 2-oxo-6,7-ethylenedioxy- (1, 3, 4, 5 or 8-) 1, 2, 3, 4-tet Rahydroquinolyl. Examples of the cycloalkyl lower alkyl group include cycloalkylalkyl groups having 3 to 16 carbon atoms whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as cyclopropylmethyl, cyclohexylmethyl, 2-cyclopropylethyl, 1-cyclobutylethyl groups, 3-cyclopentylpropyl, 4-cyclohexylbutyl, 5-cycloheptylpentyl, 6-cyclooctylhexyl, 1, l-dimethyl-2-cyclononylethyl, 2-methyl-3-cyclodecylpropyl, cycloundecylmethyl, 2-cyclododecylethyl, 1-cyclo-tridecylethyl, 3-cycotetradecylpropyl, 4-cyclopentadecylbutyl, and 5-cyclohexadecylpentyl. Examples of the pyridyl lower alkyl group include pyridylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3 or 4) pyridylmethyl groups, 2 - [(2, 3 or 4- ) pyridyl] ethyl, l - [(2, 3 or 4) pyridyl] ethyl, 3 - [(2, 3 or 4) pyridyl] propyl, 4 - [(2, 3 or 4) pyridyl] butyl, 1, 1-dimethyl-2 - [(2, 3 or 4) pyridyl] ethyl, 5 - [(2, 3 or 4) pyridyl] pentyl, 6 - [(2, 3 or 4) pyridyl] hexyl , l - [(2, 3 or 4-) pyridyl] isopropyl, and 2-methyl-3- [(2, 3 or 4) pyridyl] propyl. Examples of the lower alkyl substituted with an amino group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group include linear or branched alkyl groups having 1 to 6 carbon atoms and an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl groups, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1, l-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3- isopropylareneopropyl, 4-butylaminobutyl, 5- pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino) methyl, 2- (N, N-dimethylaraine) ethyl, 2- (N-methyl-N-hexylamino) ethyl, formylaminomethyl, acetylaminoraethyl , 1-propionylaminoethyl, 2-acetylaminoethyl, 3-butyrylaminopropyl, 4-pentanoylaminobutyl, 5-hexanoylaminopentyl, 6-acetylaminohexyl, N-methyl-N-acetylaminomethyl, 2- (N-ethyl-N-propanoylamino) ethyl, (N-ethyl) -N-butyrylamino) methyl, 2- (N-methyl-N-hexanoylamino) ethyl, and 3- (N, N-dimethylamino) propyl. Examples of the lower alkoxy lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms having a straight or branched alkoxy group having 1 to 6 carbon atoms, as a substituent such as methoxymethyl, 1-ethoxyethyl, 2-methoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl, and 3-methoxypropyl. Examples of the lower alkyl group substituted with 1, 2, 3, 4-tetrahydroisoquinolylcarbonyl include 1, 2, 3, 4-tetrahydroisoquinolylcarbonyl-alkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups (1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, -tetrahydroisoquinolylcarbonylmethyl, 2 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroisoquinolylcarbonyl] ethyl, l - [(d, 2, 3, 4, 5, 6, 7 or 8-) l, 2,3,4-tetrahydroisoquinolylcarbonyl) ethyl, 3 - [(1, 2, 3, 4, 5, 6, 7 u 8-) 1, 2, 3, -tetrahydroisoquinolylcarbonyl] propyl, 4 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroisoquinolylcarbonyl] butyl, 1, l-dimethyl-2- [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydroisoquinolylcarbonyl] ethyl, 5 - [(1, 2, 3, 4, 5 , 6, 7 or 8-) 1, 2, 3, 4-tetrahydroisoquinolylcarbonyl] pentyl, 6 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroisoquinolylcarbonyl ] hexyl, 1 - [(1, 2, 3, 4, 5, 6, 7 or 8-) l, 2,3,4-tetrahydroisoquinolylcarbonyl] isopropyl, and 2-methyl-3- [(1, 2, 3 , 4, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydroisoquinolylcarbonyl] propyl. Examples of the piperidinylcarbonyl group which may have, in the piperidine ring, a substituent selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a lower alkyl furyl group include piperidinylcarbonyl groups which may have, in the piperidine ring, 1 to 3 substituents selected from the group consisting of an alkoxycarbonyl group whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group whose alkyl portion is a linear or branched alkyl group which has 1 to 6 carbon atoms, and a furylalkyl group whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms. carbon such groups (1, 2, 3 or 4-) piperidinylcarbonyl, l-benzyl- (2, 3 or 4-) piperidinylcarbonyl, 1- (2 or 3-furylmethyl- (2, 3 or 4-) piperidinylcarbonyl, 1 - (2-phenylethyl) -2,3 or 4- piperidinylcarbonyl, 1--. { 2 - [(1 or 2-) furyl] ethyl} - (2 , 3 or 4-) piperidinylcarbonyl, 1- (1-phenylethyl) - (2,3- or 4-piperidinylcarbonyl, 1 -. {3 - [(1 or 2) furyl] propyl].} - (2, 3 or 4- piperidinylcarbonyl, 1- (3-phenylpropyl) - (2,3- or 4-piperidinylcarbonyl, 1-. {1 - [(1 or 2-) furyl] ethyl].} - (2, 3 or 4) - piperidinylcarbonyl, 1- (4-phenylbutyl) - (2, 3 or 4-piperidinylcarbonyl, 1 -. {4 - [(1 or 2) furyl] butyl].} - (2, 3 or 4-piperidinylcarbonyl 1- (5-phenylpentyl) - (2, 3 or 4-piperidinylcarbonyl, 1- {5 - [(1 or 2-) furyl] pentyl].} - (2, 3 or 4-piperidinylcarbonyl) - (6-phenylhexyl) - (2, 3 or 4-piperidinylcarbonyl, 1- (6 - [(1 or 2) furyl] hexyl].} - (2, 3 or 4-piperidinylcarbonyl, 1,2-dibenzyl) - (3, 4, 5 or 6-piperidinylcarbonyl, 1, 3-di (l or 2) furylmethyl- (2, 4, 5 or 6-piperidinylcarbonyl, 1, 3, 5-tribenyl- (2, 4 or 6 - piperidinylcarbonyl, 1, 2,6-tri (l or 2-) furylmethyl- (3, 4 or 5-piperidinylcarbonyl, l-benzyl-3- (1 or 2-) furylmethyl- (2, 4, 5 or 6-) Piperidinylcarbonyl, 1- { 1 - [(1 or 2-) furyl] ethyl]} - (2, 3 or 4-) piperidinylcarbonyl, 1-methoxycarbonyl- (2, 3 or 4-) piperidinylcarbonyl, 1-ethoxycarbonyl- (2, 3 or 4-) piperidinylcarbonyl, 1-propoxycarbonyl- (2, 3 or 4-) piperidinylcarbonyl, 1-butoxycarbonyl - (2, 3 or 4-) piperidinylcarbonyl, 1-tert-butoxycarbonyl- (2, 3 or 4-) ) piperidinylcarbonyl, 1-pentyloxycarbonyl- (2, 3 or 4-) piperidinylcarbonyl, 1-hexyloxycarbonyl- (2, 3 or 4-) piperidinylcarbonyl, 1,2-dimethoxycarbonyl- (3, 4, 5 or 6-) piperidinylcarbonyl, , 2,6-triethoxycarbonyl- (3, 4 or 5-) piperidinylcarbonyl, 1- (1 or 2-) furylmethyl-3-tert-butoxycarbonyl- (3, 4, 5 or 6-) piperidinylcarbonyl, l-benzyl-2 -methoxycarbonyl- (2, 4, 5 or 6-) piperidinylcarbonyl, and 1- (1 or 2-) furylmethyl-2,4-dimethoxycarbonyl- (3, 5 or 6-) piperidinylcarbonyl. Examples of the thiazolidinyl lower alkanoyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinyl-alkanoyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkanoyl portion is a linear alkanoyl group or branched having 2 to 6 carbon atoms such as 2- [(2, 3, 4 or 5) thiazolidinyl] acetyl, 3 - [(2, 3, 4 or 5-) thiazolidinyl] propionyl groups, 2 - [( 2, 3, 4 or 5 -) thiazolidinyl] propionyl, 4 - [(2, 3, 4 or 5) thiazolidinyl] butyryl, 5 - [(2, 3, 4 or 5-) l, 2,4-thiazolidinyl ] pentanoyl, 6 - [(2, 3, 4 or 5 -) thiazolidinyl] hexanoyl, 2, 2-dimethy1-3- [(2, 3, 4 or 5) thiazolidinyl] propionyl, 2-methyl-3- [ (2, 3, 4 or 5) thiazolidinyl] propionyl, 2,4-dioxo- (3 or 5) thiazolidinyl acetyl, 3- [2-oxo- (3, 4 or 5- ) thiazolidinyl] propionyl, 2- [4-oxo- (2, 3 or 5) thiazolidinyl] propionyl, 4- [5-oxo- (2, 3 or 4) thiazolidinyl] butyryl, 5- [2, 5- dioxo- - (3 or 4-) thiazolidinyl] pentanoyl, 6- - [2,4,5-trioxo-3-thiazolidinyl] hexanoyl, 2- [4,5-dioxo- - (2 or 3- iimethyl-3- [2, 4-d.ioxo- (3 or 5) thiazolidinyl] propionyl, and 2-methyl-3- [2, -dioxo- (3 or 5) thiazolidinyl] propionyl Examples of the piperidinyl group which can be substituted in the piperidine ring with a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group and a furyl lower alkyl group include piperidinyl groups which can be substituted in the ring of piperidine with 1 to 3 groups selected from the group consisting of an alkoxycarbonyl group whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group whose alkyl portion is a linear alkyl group or ram ized having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms, a benzoyl group, and a furylalkyl group whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms. carbon such as groups (1, 2, 3 or 4-) piperidinyl, 1-benzyl- (2, 3 or 4-) piperidinyl, 1- (2 or 3) furylmethyl- (2, 3 or 4-) piperidinyl, 1- (2-phenylethyl) - (2, 3 or 4-) piperidinyl, 1-. { 2 - [(1 or 2-) furyl] ethyl} - (2, 3 or 4-) piperidinyl, 1- (1-phenylethyl) - (2, 3 or 4-) piperidinyl, 1- (3 - [(1 or 2) furyl] propyl].] - - ( 2, 3 or 4-) piperidinyl, 1- (3-phenylpropyl) - (2, 3 or 4) piperidinyl, 1- { 1 - [(1 or 2-) furyl] ethyl].} - - ( 2, 3 or 4-) piperidinyl, 1- (4-phenylbutyl) - (2, 3 or 4) piperidinyl, 1- {4 - [(1 or 2-) furyl] butyl].} - - ( 2, 3 or 4-) piperidinyl, 1- (5-phenylpentyl) - (2, 3 or 4-) piperidinyl, 1- (5 - [(1 or 2) furyl] pentyl].} - (2, 3 or 4-) piperidinyl, 1- (6-phenylhexyl) - (2, 3 or 4) piperidinyl, 1- {6 - [(1 or 2) furyl] hexyl].} - (2, 3 or 4-) piperidinyl, 1,2-dibenzyl- (3, 4, 5 or 6-) piperidinyl, 1,3-di (l or 2-) furylmethyl- (2, 4, 5 or 6-) piperidinyl, 1,3,5-tribenzyl- (2, 4 or 6-) piperidinyl, 1, 2,6-tri (l or 2-) furylmethyl- (3, 4 or 5-) piperidinyl, l-benzyl-3- ( 1 or 2-) furylmethyl- (2, 4, 5 or 6-) piperidinyl, 1- { 1 - [(1 or 2-) furyl] ethyl].} - (2, 3 or 4-) piperidinyl , 1-benzoyl- (2, 3 or 4-) piperidinyl, 1,2-dibenzoyl- (3, 4, 5 or 6-) piperidinyl, 1, 3, 5-tribenzoyl- (2, 4 or 6-) piperidinyl, l-methyl- (2, 3 or 4-) piperidinyl, l-ethyl- (2, 3 or 4-) piperidinyl, l-propyl- (2, 3 or 4-) piperidinyl, 1-isopropyl- (2, 3 or 4-) piperidinyl, 1-butyl- (2, 3 or 4-) piperidinyl, 1-isobutyl- (2, 3 or 4-) piperidinyl, 1-tert-butyl- (2 , 3 or 4-) piperidinyl, 1-pentyl- (2, 3 or 4-) piperidinyl, l-hexyl- (2, 3 or 4-) piperidinyl, 1,2-dimethyl- (3, 4, 5 or 6) -) piperidinyl, 1, 2, 6-trimethyl- (3, 4 or 5-) piperidinyl, l-methyl-3-benzyl- (3, 4, 5 or 6-) piperidinyl, 1- benzoyl-2-methyl- (2, 4, 5 or 6-) piperidinyl, 1- (1 or 2-) furylmethyl-2,4-dimethyl- (3, 5 or 6-) piperidinyl, 1-methoxycarbonyl- (2 , 3 or 4-) piperidinyl, 1-ethoxycarbonyl- (2, 3 or 4-) piperidinyl, 1-propoxycarbonyl- (2, 3 or 4-) piperidinyl, 1-butoxycarbonyl- (2, 3 or 4-) piperidinyl, 1-tert-butoxycarbonyl- (2, 3 or 4) piperidinyl, 1-pentyloxycarbonyl- (2, 3 or 4-) piperidinyl, 1-hexyloxycarbonyl- (2, 3 or 4-) piperidinyl, 1,2-dimethoxycarbonyl- (3, 4, 5 or 6-) piperidinyl, 1, 2, 6-triethoxycarbonyl- (3, 4 or 5-) piperidinyl, l-methyl-3-tert-butoxycarbonyl- (3, 4, 5 or 6-) piperidinyl, 1-benzoyl-2-methoxycarbonyl- (2, 4, 5 or 6-) piperidinyl, 1- (1 or 2-) furylmethyl-2,4-dimethoxycarbonyl- (3, 5 or 6-) piperidinyl, and -benzyl-2, 4-dimethoxycarbonyl- (3, 5 or 6-) piperidinyl. Examples of the lower alkylcarbonyl group substituted with one group: [Formula 40] (hereinafter referred to as "group A") include carbonylalkyl groups substituted with group A whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as carbonylmethyl groups substituted with group A, carbonylethyl substituted with group 2-A , carbonylethyl substituted with group 1-A, carbonylpropyl substituted with group 3-A, carbonyl butyl substituted with group 4-A, carbonylethyl substituted with group 1, l-dimethyl-2-A, carbonylpentyl substituted with group 5-A, carbonylhexyl substituted with group 6-A, carbonyl isopropyl substituted with group 1-A, and carbonylpropyl substituted with 2-methyl-3-A group. Examples of the lower alkylcarbonyl group substituted with one group: [Formula 41] wherein R34 is an oxo group or a phenyl group, and d is an integer from 0 to 3 (hereinafter referred to as "group B"), include carbonylalkyl groups substituted with group B whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as carbonylmethyl groups substituted with group B, carbonylethyl substituted with group 2-B, carbonylethyl substituted with group 1-B, carbonylpropyl substituted with group 3-B, carbonyl butyl substituted with group 4-B, carbonylethyl substituted with group 1, l-dimethyl-2-B, carbonylpentyl substituted with group 5-B, carbonylhexyl substituted with group 6-B, carbonylisopropyl substituted with group 1-B, and carbonylpropyl substituted with group 2-methyl-3-B. Examples of the pyrrolidinyl lower alkyl group include pyrrolidinylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1-, 2-, or 3-) pyrrolidinylmethyl, 2 - [(1-, 2-, or 3-) pyrrolidinyl] ethyl, 1- [ (1-, 2-, or 3-) pyrrolidinyl] ethyl, 3 - [(1-, 2-, or 3-) pyrrolidinyl] propyl, 4 - [(1-, 2-, or 3 -)? Irrolidinil] butyl, 5 - [(1-, 2-, or 3-) pyrrolidinyl] pentyl, 6 - [(1-, 2-, or 3-) pyrrolidinyl] hexyl, 1, l-dimethyl-2- [(1- , 2-, or 3-) pyrrolidinyl] ethyl, and 2-methyl-3 - [(1-, 2-, or 3-) pyrrolidinyl] propyl. Examples of the morpholino lower alkyl group include morpholinoalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2-, 3- or 4-) morpholinomethyl groups, 2- [(2-3 - or 4-) morpholino] ethyl, l - [(2-, 3- or 4-) morpholino] ethyl, 3 - [(2-, 3- or 4-) morpholino] propyl, 4 - [(2-, 3- or 4-) morpholino] butyl, 5 - [(2-, 3- or 4-) morpholino] pentyl, 6 - [(2-, 3- or 4-) morpholino] hexyl, 1, l-dimethyl-2- [(2-, 3- or 4-) morpholino] ethyl, and 2-methyl-3- [(2-, 3- or 4- ) morpholino] propyl. Examples of the lower alkenyl phenyl group include phenylalkenyl groups whose alkenyl portion is a straight or branched alkenyl group having 2 to 6 carbon atoms and which have 1 to 3 double bonds such as styryl groups, 3-phenyl-2-propenyl group ( trivial name: cinnamyl group), 4-phenyl-2-butenyl, 4-phenyl-3-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 6-phenyl-5-hexenyl, 6-phenyl -4-hexenyl, 6-phenyl-3-hexenyl, 4-phenyl-1,3-butadienyl, and 6-phenyl-1,3,5-hexatrienyl. Examples of the anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring include anilinocarbonylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 carbon atoms. linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as anilinocarbonylmethyl groups, 2-anilinocarbonylethyl, 1-anilinocarbonylethyl, 3-anilinocarbonylpropyl, 4-anilinocarbonylbutyl, 5-anilinocarbonylpentyl, 6-anilinocarbonylhexyl, 1, l-dimethyl-2-anilinocarbonylethyl, 2-methyl-3-anilinocarbonylpropyl, (4-methylanilinocarbonyl) methyl, 2- (3-methylanilinocarbonyl) ethyl, 3- (4-methylanilinocarbonyl) propyl, 1- (2-ethylanilinocarbonyl) ethyl, 4- (3-ethylanilinocarbonyl) butyl, 5- (4-ethylanilinocarbonyl) pentyl, 6- (4- isopropylanilinocarbonyl) hexyl, 1, l-dimethyl-2- (3-butylanilinocarbonyl) ethyl, 2-methyl-3- (4-pentylanilinocarbonyl) propyl, 4-hexylanilinocarbonylmethyl, 3,4-dimethylanilinocarbonylmethyl, 3,4-diethylanilinocarbonylmethyl, 2, 4-dimethylanilinocarbonylmethyl, 2,5-dimethylanilinocarbonylmethyl, 2,6-dimethylanilinocarbonylmethyl, and 3,4,5- trimethylanilinocarbonylmethyl. Examples of the piperazinyl lower alkyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group which has 1 to 6 carbon atoms and a phenylalkyl group which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1-, 2- or 3-) piperazinyl] methyl, 2 - [(1-, 2- or 3-) piperazinyl] ethyl, 1 - [(1-, 2- or 3)] groups -) pipera zinyl] ethyl, 3 - [(l-, 2- or 3-) piperazinyl] propyl, 4 - [(1, 2, 3 or 3) piperazinyl] butyl, 5 - [(1-, 2- or 3- ) piperazinyl] pentyl, 6- [(1-, 2- or 3-) piperazinyl] hexyl, 1, l-dimethyl-2- [(1-, 2- or 3-) piperazinyl] ethyl, 2-methyl-3 - [(1-, 2- or 3-) piperazinyl] propyl, [1-methyl- (2-, 3- or 4-) piperazinyl] methyl, 2- [1-ethyl- (2-, 3- or 4 -) piperazinyl] ethyl, 1- [4-propyl- (1-, 2- or 3-) piperazinyl] ethyl, 3- [3-isopropyl- (1- , 2-, A-, 5- or 6-) piperazinyl] propyl, 4- [2-butyl- (1-, 3-, A-, 5- or 6-) piperazinyl] butyl, 5- [1-isobutyl - (2-, 3- or 4-) piperazinyl] pentyl, 3- [4-methyl- (1-, 2- or 3-) piperazinyl] propyl, 6- [1-tert-butyl- (2-, 3 - or 4-) piperazinyl] hexyl, 1, l-dimethyl-2- [4-pentyl- (1-, 2- or 3-) piperazinyl] ethyl, [1,2-dimethyl- (3-, A-, 5- or 6-) piperazinyl] methyl, [1, 2, 6-trimethyl- (3-, 4- or 5-) piperazinyl] methyl, and 2- [4- (3,4-methylenedioxybenzyl) - (1- , 2- or 3-) piperazinyl] ethyl. Examples of the amidino lower alkyl group which may have a lower alkyl group as a substituent include amidinoalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 or 2 linear alkyl groups or branched having 1 to 6 carbon atoms such as amidinomethyl, 2-amidinoethyl, 1-amidinoethyl, 3-amidinopropyl, 4-amidinobutyl, 5-amidinopentyl, 6-amidinohexyl, 1, 1-dimethyl-2-amidinoethyl, 2- methyl-3-amidinopropyl, N, N-dimethylamidinomethyl, 2- (N, N-dimethylararidino) ethyl, 1- (N-raethylararidino) ethyl, 3- (N-ethylamidino) propyl, 4- (Nn-propylamino) propyl, 5- (Nn-pentylamidino) pentyl, 6- (Nn-hexylamidino) hexyl, and (N-methyl-N-ethylamidino) methyl. Examples of the carbazolyl group which may have a lower alkyl group as a substituent on the ring of Carbazole include carbazolyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the carbazole ring such as (1-, 2-, 3- or 4-) carbazolyl groups, -methyl- (l-, 2-, 3- or 4-) carbazolyl, 9-ethyl- (l-, 2-, 3- or 4-) carbazolyl, l-ethyl- (2-, 3-, A- , 5-, 6-, 7-, 8- or 9-) carbazolyl, 2-n-pro? Il- (l-, 3-, 4-, 5-, 6-, 8- or 9-) carbazolyl, 3-n-butyl- (1-, 2-, A-, 5-, 6-, 7-, 8- or 9-) carbazolyl, 4-n-pentyl- (1-, 2-, 3-, 5 -, 6-, 7-, 8- or 9-) carbazolyl, 5-n-hexyl- (1-, 2-, 3-, 4-, 6-, 7-, 8- or 9-) carbazolyl, 6 , 9-dimethyl- (1-, 2-, 3-, A-, 5-, 7- or 8-) carbazolyl, and 1, 7, 8-trityl- (2-, 3-, A-, 5- , 6-, 7-, 8- or 9-) carbazolyl. Examples of the amidino group which may have a lower alkyl group as a substituent include amidino groups which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents such as amidino, N, N-dimethylamidino groups, N-methylamidino, N-ethylamidino, Nn-propylamidino, Nn-butylamidino, Nn-pentylamidino, Nn-hexylamidoino, N, N-diethylamidoino, and N-methyl-N-ethylamidoino. Examples of the phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group), include, in addition to the phenyl lower alkyl groups described above, groups phenylalkyl whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 3 carbon atoms; to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) such as 3,4-methylenedioxybenzyl groups, 3,4-trimethylenedioxybenzyl, 2- (2,3-ethylenedioxyphenyl) ethyl, 1- ( 3,4-trimethylenedioxyphenyl) ethyl, 3- (2,3-tetramethylenedioxyphenyl) propyl, 4- (3,4-methylenedioxyphenyl) butyl, 5- (2,3-ethylenedioxyphenyl) pentyl, 6- (3,4-trimethylenedioxyphenyl) hexyl, 1, l-dimethyl-2- (2,3-methylenedioxyphenyl) ethyl, 2-methyl-3- (3,4-ethylenedioxyphenyl) propyl, 2-methoxybenzyl, 2- (2-methoxyphenyl) ethyl, 2- ( 3-methoxyphenyl) ethyl, 2- (4-methoxyphenyl) ethyl, 4-methoxybenzyl, 1- (2-ethoxyphenyl) ethyl, 3- (3-ethoxyphenyl) propyl, 4- (4-ethoxyphenyl) butyl, 5- (4 -isopropoxyphenyl) pentyl, 6- (3-butoxyphenyl) hexyl, 1,1-dimethyl-2- (4-pentyloxyphenyl) ethyl, 2-methyl-3- (4-hexyloxyphenyl) propyl, 3,4-dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2, 5-diraethoxybenzyl, 2,6-dimethoxybenzyl, and 3,4,5-trimethoxybenzyl. Examples of the oxalyl group substituted with a piperazinyl group which may have, in the piperazine ring, 1 to 3 substituents selected from the group consisting of phenyl lower alkyl group (which may have, in the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group) and a lower alkyl pyridyl group include piperazinyl substituted oxalyl groups which may having, in the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenylalkyl group whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring) , 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) and a pyridylalkyl group whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as 4- (3,4-methylenedioxybenzyl) - (1-, 2- or 3-) piperazinyloxalyl, 4- (2-, 3- or 4-pyridyl-phenyl) - (1-, 2- or 3-) piperazinyloxalyl, 4- (3,4-dira-ethoxy-benzyl) - (1-, 2- or 3-) piperazinyloxalyl, 4- (2,3-methylenedioxybenzyl) - ( 1-, 2- or 3-) piperazinyloxalyl, 4- (3, 4-ethylenedioxybenzyl) - (1-, 2- or 3-) piperazinyloxalyl, 4- [2- (2-, 3- or 4-pyridyl) ethyl ] - (1-, 2- or 3-) piperazinyloxalyl, 4- [3- (2-, 3- or 4-pyridyl) propyl- (1-, 2- or 3-) piperazinyloxalyl, 2,4-bis ( 2-, 3- or 4-pyridylmethyl) - (1-, 2- or 3-) piperazinyloxalyl, 2- (3,4-methylenedioxybenzyl) -4- (2-, 3- or 4-pyridylmethyl) - (1- , 2- or 3-) piperazinyloxalyl, and 2,3,4- i 70 tri (2-, 3- or 4-pyridylmethyl) - (1-, 2- or 3-) piperazinyloxalyl. Examples of the lower alkyl group substituted with cyano include cyanoalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl groups, 5-cyanopentyl, 6-cyanohexyl, 1, l-dimethyl-2-cyanoethyl, and 2-methyl-3-cyanopropyl. Examples of the 5- to 7-membered saturated heterocyclic ring formed by joining R36 and R37 to each other, together with nitrogen atoms attached thereto, through or not through a nitrogen atom, an oxygen atom, or a sulfur atom include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and houropiperazinyl groups. Examples of the saturated or unsaturated 5- to 10-membered heterocyclic ring formed by joining R14 and R15 to each other, together with nitrogen atoms attached thereto, through or not through a nitrogen atom, an oxygen atom, or an atom of sulfur include 1, 2, 3, 4, 5, 6-hexahydropyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, homopiperazinyl, homopiperidinyl, thiazolidinyl, 1, 2, 5, 5, 6-tetrahydropyridyl, pyrrolyl, pyrazolyl, imidazolyl, 2-pyrrolinyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, 1,2-dihydropyridyl, 1,2-dihydroquinolyl, 1,2,3,4- tetrahydroquinolyl, 1, 2, 3, 4-tetrahydroisoquinolyl, 1,2- dihydroisoquinolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 3, -dihydro-2H-l, 4-benzooxazinilo, 3,4-dihydro-2H-1, - benzothiazolidinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1, 2, 3, -tetrahydrocinnolinyl, 1,2,3,4-tetrahydroftalazinyl, 1,2,3,4-tetrahydroquinazolinyl, 1, 2 -dihidroquinoxalinilo, 3,4- dihydroquinoxalinyl, 1, 4-dihydroquinoxalinyl, 1,2-dihidrocinnolinilo, 1, 2-dihydrophthalazinyl, 3,4-dihydrophthalazinyl, 1, 2-dihydroquinazolinyl, 3,4-dihydroquinazolinyl, indazolyl, indazolinyl, 6 -azabicyclo [3, 2, 1] octyl, 3-aza-spiro [5, 5] undecyl, and thiazolidinyl. Preferably, R14 and R15, together with the nitrogen atom to which they are attached, are bonded together, directly or via a nitrogen atom to form a saturated 6-membered heterocyclic group. Most preferably, they include piperidinyl and piperazinyl groups. Examples of the phenyl lower alkoxy group include phenylalkoxy groups whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms such as benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy groups, phenylpentyloxy, 6-phenylhexyloxy, 1, l-dimethyl-2-phenylethoxy, and 2-methyl-3-phenylpropoxy. Examples of the lower alkyl group substituted with phenyl having 1 or 2 phenyl groups which can be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which can have a lower alkanoyl group as a substituent, an alkoxycarbonyl group lower, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent , a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group; and which may have a pyridyl group in the lower alkyl group include, in addition to the phenyl lower alkyl groups described above, alkyl groups substituted with phenyl having 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of group consisting of a linear or branched alkanoyl group having 1 to 6 carbon atoms, an amino group which may have 1 or 2 linear or branched alkanoyl groups having 1 to 6 carbon atoms as substituents, a linear or alkoxycarbonyl group branched having 1 to 6 carbon atoms, a cyano group, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 carbon atoms halogen as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a phenylalkoxy group whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms, a hydroxy group, and a linear alkylenedioxy group or branched having 1 to 4 carbon atoms; which may have a pyridyl group in the alkyl group, and which alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 1-phenyl-1- (2, 3 or 4) pyridyl groups methyl, 1, 1-diphenylmethyl, l, l-di (4-fluorophenyl) methyl, 1-phenyl-1- (4-methoxyphenyl) methyl, 3,4- methylenedioxybenzyl, 3, 4-etilendioxibencilo, 3,4-trimetilendioxibencilo , 2, 5-difluorobenzyl, 2,4-difluorobenzyl, 3, 4-difluorobenzyl, 3, 5-difluorobenzyl, 2, 6-difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl, 3 , 5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 3, 4-dimethylbenzyl, 2, 3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4 -cianobencilo, 2-cyanobenzyl, 3-cyanobenzyl, 4-methoxybenzyl, 2,3-dichlorobenzyl, 2, 4-dichlorobenzyl, 2, 5-dichlorobenzyl, 3,4-dichlorobenzyl, 2, 6-dichlorobenzyl, 4-fluorobenzyl, 3 -fluorobenzyl, 2-fluorobenz it, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluororatoxybenzyl, 4- methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2- (4-methoxyphenyl) ethyl, 2- (4-fluorophenyl) ethyl, 2- (4 chlorophenyl) ethyl, 2- (3-methoxyphenyl) ethyl, 2- (4-methylphenyl) ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4-nitrobenzyl, 4- (4-methoxyphenyl) butyl, 2- (4-methylphenyl) ethyl, 4-tert-butoxicarbonilbencilo, 3-chloro-6-methoxybenzyl, 4-acetylaminobenzyl, 4-nitro-3-methylbenzyl, 4-hydroxybenzyl, 3-hydroxybenzyl, 2-hydroxybenzyl, 4-tert -butirilbencilo, 4-benzyloxybenzyl, 4-pivaloilbencilo, 2- (4-acetylphenyl) ethyl, 1- (3-propionylphenyl) ethyl, 3- (2-butyrylphenyl) propyl, 4- (4-pentanoilfenil) butyl, 5- ( 3-hexanoylphenyl) pentyl, 6- (2,4-diacetylphenyl) hexyl, 1,1-dimethyl-2- (2,4,6-triacetylphenyl) ethyl, 2-methyl-3- (3,4-diacetylphenyl) propyl 2- (4-aminophenyl) ethyl, 1- (3-propionylaminophenyl) ethyl, 3- (2-butyrylaminophenyl) propyl, 4- (4-pentanoylamino) phenylbutyl, 5- (hexanoylamino) enyl) pentyl, 6- (N-Acetyl-N-propionylaminophenyl) hexyl, 1,1-dimethyl-2- (3,4-diaminophenyl) ethyl, 2-methyl-3- (3,4,5-triacetylaminophenyl) propyl, 2- ( 2-ethoxycarbonylphenyl) ethyl, 1- (3-propoxycarbonylphenyl) ethyl, 3- (4-pentyloxycarbonylphenyl) propyl, 4- (3-hexyloxycarbonylphenyl) butyl, 5- (3,4-dimethoxycarbonylphenyl) pentyl, 6- (3,4 , 5-triethoxycarbonylphenyl) hexyl, 1, l-dimethyl-2- (4- butoxycarbonylphenyl) ethyl, 2-methyl-3- (4-methoxycarbonylphenyl) propyl, 2- (2-cyanophenyl) ethyl, 1- (3-cyanophenyl) ethyl, 3- (4-cyanophenyl) propyl, 4- (2-cyanophenyl) butyl, 5- (3-cyanophenyl) pentyl, 6- (4-cyanophenyl) hexyl, 1, l-dimethyl-2- (2,4-dicyanophenyl) ethyl, 2-methyl-3- (2,, 6-) tricyophenyl) propyl, 2- (2-nitrophenyl) ethyl, 1- (3-nitrophenyl) ethyl, 3- (4-nitrophenyl) propyl, 4- (2-nitrophenyl) butyl, 5- (3-nitrophenyl) pentyl, - (4-nitrophenyl) hexyl, 1, l-dimethyl-2- (2,4-dinitrophenyl) ethyl, 2-methyl-3- (2,4,6-trinitrophenyl) propyl, 2- (2-phenylphenyl) ethyl , 1- (3-phenylphenyl) ethyl, 3- (4-phenylphenyl) propyl, 4- (2-phenylphenyl) butyl, 5- (3-phenylphenyl) pentyl, 6- (4-phenylphenyl) hexyl, 1, 1- dimethyl-2- (2, 4-diphenylphenyl) ethyl, 2-methyl-3- (2,4,6-triphenylphenyl) propyl, 2- (2-fluorophenyl) ethyl, 1- (3-bromophenyl) ethyl, 3- (4-iodophenyl) propyl, 4- (2-bromophenyl) butyl, 5- (3-chlorophenyl) pentyl, 6- (4-bromophenyl) hexyl, 1, l-dimethyl-2- (2,4-dichlorophen) nil) ethyl, 2-methyl-3- (2,4,6-trifluorophenyl) propyl, 2- (2-ethylphenyl) ethyl, 1- (3-propylphenyl) ethyl, 3- (4-butylphenyl) propyl, 4- (2-pentylphenyl) butyl, 5- (3-hexylphenyl) pentyl, 6- (4-trifluoromethylphenyl) hexyl, 1, l-dimethyl-2- (2,4-dimethylphenyl) ethyl, 2-methyl-3- [2 , 4,6-tri (trifluoromethyl) phenyl] propyl, 2- (2-ethoxyphenyl) ethyl, 1- (3-propoxyphenyl) ethyl, 3- (4-butoxyphenyl) propyl, 4- (2-pentyloxyphenyl) butyl, - (3-hexyloxyphenyl) pentyl, 6- (4- trifluoromethoxyphenyl) hexyl, 1, l-dimethyl-2- (2,4-dimethoxyphenyl) ethyl, 2-meth1-3- [2,4,6-tri (trifluoromethoxy) phenyl] propyl, 2- (2-benzyloxyphenyl) ethyl , 1- [3- (2-phenylethoxy) phenyl] ethyl, 3- [4- (3-phenylpropoxy) phenyl] propyl, 4- [2- (4-phenylbutoxy) phenyl] butyl, 5- [3- (5 phenylpentyloxy) phenyl] pentyl, 6- [4- (6-phenylhexyloxy) phenyl] hexyl, 1, l-dimethyl-2- (2,4-dibenzyloxyphenyl) ethyl, 2-methyl-3- (2, 4,6 -tribenzyloxyphenyl) propyl, 2- (2-hydroxyphenyl) ethyl, 1- (3-hydroxyphenyl) ethyl, 3- (4-hydroxyphenyl) propyl, 4- (2-hydroxyphenyl) butyl, 5- (3-hydroxyphenyl) pentyl, 6- (4-hydroxyphenyl) hexyl, 1, l-dimethyl-2- (2,4-dihydroxyphenyl) ethyl, 2-methyl-3- (2,4,6-trihydroxyphenyl) propyl, 2- (3,4- methylenedioxyphenyl) ethyl, 1- (2, 3-ethylenedioxyphenyl) ethyl, 3- (3, 4-trimetilendioxifenil) propyl, 4- (3,4-tetrametilendioxifenil) butyl, 5- (3, 4-methylenedioxyphenyl) pentyl, 6- (3,4-ethylenedioxyphenyl) hexyl, 1, l-dimethyl-2- (3,4-methylenedioxy) ethyl, and 2-methyl-3- (3,4-methylene) dioxyphenyl) propyl. Preferably, they include phenyl substituted lower alkyl groups which can be substituted on the phenyl ring with group (s), as substituent (s), selected from the group consisting of a lower alkanoyl group, an amino group which can have a group lower alkanoyl as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group. Examples of the pyridyl lower alkyl group which may have, in the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent include, in addition to the lower alkyl pyridyl groups described above, pyridylalkyl groups which may have, in the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxy group and a linear or branched alkyl group having 1 to 6 carbon atoms which they may have 1 to 3 hydroxy groups as substituents, and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [2-methyl- (3, 4, 5 or 6-) pyridyl] methyl groups , [2-methyl-3-hydroxy-5-hydroxymethyl- (4 or 6-) pyridyl] methyl, 2- [3-ethyl- (2, 4, 5 or 6-) pyridyl] ethyl, 1- [4 -propyl- (2, 3, 5 or 6-) pyridyl] ethyl, 3- [2-butyl- (3, 4, 5 or 6-) pyridyl] propyl, 4- [3-pentyl- (2, 4, 5 or 6-) pyridyl] butyl, 1, l-dimethyl-2- [4-hexyl- (2, 3, 5 or 6-) pyridyl] ethyl, 5- [2,3-dimethyl- (4, 5 or 6-) pyridyl] pentyl, 6- [2, 4, 6-trimethyl- (3 or 5- ) pyridyl] hexyl, 1- [2-hydroxy- (2, 3, 5 or 6-) pyridyl] isopropyl, 2-methyl-3- [3-hydroxy- (2, 4, 5 or 6-) pyridyl] propyl , [2-hydroxy- (3, 4, 5 or 6-) pyridyl] methyl, 2- [3-hydroxy- (2, 4, 5 or 6-) pyridyl] ethyl, 1- [4-hydroxy- (2 , 3, 5 or 6-) pyridyl] ethyl, 3- [2-hydroxy- (3, 4, 5 or 6-) pyridyl] propyl, 4- [3-hydroxy- (2, 4, 5 or 6-) pyridyl] butyl, 1, l-dimethyl-2- [4-hydroxy- (2, 3, 5 or 6-) pyridyl] ethyl, 5- [2,3-dihydroxy- (4, 5 or 6-) pyridyl] pentyl, 6- [2, 4, 6-trihydroxy- (3 or 5-) pyridyl] hexyl, [2-hydroxymethyl- (3, 4, 5 or 6-) pyridyl] methyl, 2- [3- (2- hydroxyethyl) - (2, 4, 5 or 6-) pyridyl] ethyl, 1- [4- (3-hydroxypropyl) - (2, 3, 5 or 6-) pyridyl] ethyl, 3- [2- (4- hydroxybutyl) - (3, 4, 5 or 6-) pyridyl] propyl, 4- [3- (5-hydroxypentyl) - (2, 4, 5 or 6-) pyridyl] butyl, 1, 1-dimethyl-2- [4- (6-hydroxyhexyl) - (2, 3, 5 or 6) pyridyl] ethyl, 5- [2, 3-di (hydroxymethyl) - (4, 5 or 6) pyridyl] pentyl, 6- [ 2, 4, 6-tri (hydroxymethyl) - (3 or 5- ) pyridyl] hexyl, 1- [2-hydroxymethyl- (2, 3, 5 or 6-) pyridyl] isopropyl, 2-methyl-3- [3- (2,3-dihydroxypropyl) - (2, 4, 5 or 6-) pyridyl] propyl, [2-butyl-3- (2, 2,4-trihydroxybutyl) - (4, 5 or 6) pyridyl] methyl, and [2-methyl-5-hydroxymethyl- (3, 4 or 6-) pyridyl] methyl. Examples of the pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring include pyrrolylalkyl groups which may have 1 to 3 alkyl groups linear or branched having 1 to 6 carbon atoms in the pyrrole ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-) pyrrolyl] methyl groups , 2 - [(1, 2 or 3) pyrrolyl] ethyl, 1 - [(1, 2 or 3) pyrrolyl] ethyl, 3 - [(1, 2 or 3) pyrrolyl] propyl, 4 - [( 1, 2 or 3) pyrrolyl] butyl, 5 - [(1, 2 or 3) pyrrolyl] pentyl, 6 - [(1, 2 or 3) pyrrolyl] hexyl, 1,1-dimethyl-2- [ (1, 2 or 3) pyrrolyl] ethyl, 2-methyl-3- [(1, 2 or 3) pyrrolyl] propyl, [1-methyl- (2 or 3) pyrrolyl] methyl, 2- [2 -ethyl- (l, 3, 4 or 5-) pyrrolyl] ethyl, 1- [3-propyl- (1, 2, 4 or 5-) pyrrolyl] ethyl, 3- [1-butyl- (2, 3 or 4-) pyrrolyl] propyl, 4- [2-pentyl- (1, 3, 4 or 5) pyrrolyl] butyl, 5- [3-hexyl- (1, 2, 4 or 5) pyrrolyl] pentyl, - [1,2-dimethyl- (3, 4 or 5-) pyrrolyl] hexyl, 1, l-dimethyl-2- [1, 2, 3-trimethyl- (4 or 5-) pyrrolyl] ethyl, and 2- methyl-3- [l-ethyl-2-methyl- (3, 4 or 5-) pyrrolyl] propyl. Examples of the benzoxazolyl lower alkyl group include benzoxazolylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4, 5, 6 or 7-) benzooxazolyl] methyl groups, 2- [ (2, 4, 5, 6 or 7) benzooxazolyl] ethyl, l - [(2, 4, 5, 6 or 7-) benzooxazolyl] ethyl, 3 - [(2, 4, 5, 6 or 7-) benzooxazolyl] propyl, 4 - [(2, 4, 5, 6 or 7-) benzooxazolyl] butyl, 5 - [(2, 4, 5, 6 or 7-) benzooxazolyl] pentyl, 6 - [(2, 4, 5, 6 or 7-) benzooxazolyl] hexyl, 1, l-dimethyl-2- [(2, 4, 5, 6 or 7- benzooxazolyl] ethyl, and 2-methyl-3- [(2, 4, 5, 6 or 7-) benzooxazolyl] propyl. Examples of the benzothiazolyl lower alkyl group include benzothiazolylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4, 5, 6 or 7-) benzothiazolyl] methyl groups, 2- [ (2, 4, 5, 6 or 7) benzothiazolyl] ethyl, l - [(2, 4, 5, 6 or 7-) benzothiazolyl] ethyl, 3 - [(2, 4, 5, 6 or 7-) benzothiazolyl] propyl, 4 - [(2, 4, 5, 6 or 7) benzothiazolyl] butyl, 5 - [(2, 4, 5, 6 or 7) benzothiazolyl] pentyl, 6 - [(2, 4, 5, 6 or 7-) benzothiazolyl] hexyl, 1, l-dimethyl-2- [(2, 4, 5, 6 or 7-) enzothiazolyl] ethyl, and 2-methyl-3- [(2, 4, 5 , 6 or 7-) benzothiazolyl] propyl. Examples of the furyl lower alkyl group include furylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2 or 3) furyl] methyl groups, 2 - [(2 or 3-) furyl] ethyl, 1- [(2 or 3-) furyl] ethyl, 3 - [(2 or 3) furyl] propyl, 4 - [(2 or 3) furyl] butyl, 5 - [(2 or 3 -) furyl] pentyl, 6 - [(2 or 3-) furyl] hexyl, 1, l-dimethyl-2- [(2 or 3-) furyl] ethyl, and 2-methyl-3 - [(2 or 3 -) furil] propyl. Examples of the thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinyl alkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and which alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4 or 5) thiazolidinylmethyl groups, - [(2, 3, 4 or 5) thiazolidinyl] ethyl, l - [(2, 3, 4 or 5) thiazolidinyl] ethyl, 3 - [(2, 3, 4 or 5) thiazolidinyl] propyl, 4 - [(2, 3, 4 or 5-) thiazolidinyl] butyl, 5 - [(2, 3, 4 or 5) thiazolidinyl] pentyl, 6 - [(2, 3, 4 or 5) thiazolidinyl] hexyl , 1, l-dimethyl-2- [(2, 3, 4 or 5) thiazolidinyl] ethyl, 2-methyl-3 - [(2, 3, 4 or 5) thiazolidinyl] propyl, [2, 4- dioxo- (3 or 5) thiazolidinyl] methyl, 2- [2-oxo- (3, 4 or 5) thiazolidinyl] ethyl, l- [4-oxo- (2, 3 or 5) thiazolidinyl] ethyl, 3- [2-oxo- (3, 4 or 5-) thiazolidinyl] propyl, 4- [5-oxo- (2, 3 or 4) thiazolidinyl] butyl, 5- [2, 5-dioxo- (3 or 4-) thiazolidinyl] pentyl, 6- [2, 4, 5-trioxo-3-thiazolidinyl] hexyl, 1- [5-dioxo- (2 or 3) thiazolidinyl] ethyl, 2- [5-dioxo- (2- or 3-) thiazolidinyl] ethyl, 1, dimethyl-2- [2, 4-dioxo- (3 or 5) thiazolidinyl] ethyl, and 2-methyl-3- [2,4-dioxo- (3 or 5) thiazolidinyl] propyl. Examples of the thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylidene alkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and which alkyl portion is a linear alkyl group or branched that has 1 to 6 carbon atoms such as (2, 4 or 5) thiazolidinylidenemethyl, (2, 4 or 5) thiazolidinylideneethyl, (2, 4 or 5) thiazolidinylidenepropyl, (2, 4 or 5-) thiazolidinylideneisopropyl groups, (2, 4 or 5) thiazolidinylidenebutyl, (2, 4 or 5) thiazolidinylidenepentyl, (2, 4 or 5) thiazolidinylidenehexyl, 4,5-dioxo-2-thiazolidinylidenemethyl, 2,5-dioxo-4-thiazolidinylidenemethyl, 2,4-dioxo-5-thiazolidinylidenemethyl, 4-oxo- (2 or 5) thiazolidinylideneethyl, 5-oxo- (2 or 4) thiazolidinylidenepropyl, and 2-oxo- (4 or 5) thiazolidinylidenebutyl. Examples of the benzoyl group which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, an amino group which can have a lower alkylsulfonyl group as a substituent, a halogen atom, an alkoxy group lower, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group which may have a group oxo as a substituent on the thiazolidine ring, and a lower alkylenedioxy group include benzoyl groups which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a halogen atom; a linear or branched alkoxy group having 1 to 6 carbon atoms; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a thiazolidinyl alkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms; a thiazolidinylidene alkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms; and a straight or branched alkylenedioxy group having 1 to 4 carbon atoms such as benzoyl, 4-cyanobenzoyl, 3,4-methylenedioxybenzoyl, 2-aminobenzoyl, 3-aminobenzoyl, 4-aminobenzoyl, 3,4-diaminobenzoyl, 2 groups, 4,6-triaminobenzoyl, 4-methoxybenzoyl, 4-trifluoromethylbenzoyl, 4-chlorobenzoyl, 3,4-difluorobenzoyl, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 3,4-dimethoxybenzoyl, 4-fluorobenzoyl, 3-cyanobenzoyl, 2-cyanobenzoyl, 2, 3-dicyanobenzoyl, 3,4,5-trithiobenzoyl, 4-methylbenzoyl, 4- (2,4-dioxothiazolidinylmethyl) benzoyl, 4- (2,4-dioxothiazolidinylidene-ethyl) benzoyl, 2-methylbenzoyl, 3- methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4-hexylbenzoyl, 3,4-diraethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4, 5-trimethylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 3-butoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3, -dietoxybenzoyl, 2,4-dimethoxybenzoyl 2, 5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, 3,4,5-trimethoxybenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-trifluoromethylbenzoyl, 2- (bromomethyl) benzoyl, 3- (2-chloroethyl) benzoyl, - (2,3-dichloropropyl) benzoyl, 4- (4-fluorobutyl) benzoyl, 3- (5-chloropentyl) benzoyl, 4- (5-bromohexyl) benzoyl, 4- (5,6-dibromohexyl) benzoyl, 3, 4-di (trifluoromethyl) benzoyl, 3,4-di (,, 4-trichlorobutyl) benzoyl, 2, -di (3-chloro-2-methylpropyl) benzoyl, 2,5-di (3-chloropropyl) benzoyl, 2 , 6-di (2,2,2-trifluoroethyl) benzoyl, 3,4,5-tri (trifluoromethyl) ben zoilo, 4- (2,2,2-trichloroethyl) benzoyl, 2-methyl- -trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-methoxy-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-ethoxy- 4-trichloromethylbenzoyl, 2-methyl-3-trifluorornethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2, 4- 2, 5-difluorobenzoyl, diiodobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3,4-difluorobenzoyl, 3,5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2, 3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-trifluorobenzoyl, 2,4-difluorobenzoyl, 3, -difluorobenzoyl, 3,4-methylenedioxybenzoyl, 3,4-trimethylenedioxybenzoyl, 2,3-ethylenedioxybenzoyl, 3,4-triraethylenedioxybenzoyl, 2,3-tetramethylenedioxybenzoyl, 2,3-methylenedioxybenzoyl, 3,4-ethylenedioxybenzoyl, and methanesulfonylaminobenzoyl. Examples of the thiazolidinyl lower alkanoyl group which can be substituted on the thiazolidine ring with a group selected from the group consisting of an oxo group and a group of the formula: [Formula 42] R; = N-N = Rb wherein R a and R b each represent a lower alkyl group, include thiazolidinyl alkylanyl groups which can be substituted on the thiazolidine ring with 1 to 3 substituents selected from the group consisting of an oxo group and a group of the formula: [Formula 43-1] = N- N = ( wherein Ra and R each represents a linear or branched alkyl group having 1 to 6 carbon atoms, and whose alkanoyl portion is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2- [(2, 3, 4 or 5-) thiazolidinyl acetyl, 3- [(2, 3, 5-) thiazolidinyl propionyl, 2- [(2, 3, 5-) thiazolidinyl propionyl, 4- [(2, 3, 5) thiazolidinyl] butyryl, 5- [(2, 3, 5) thiazolidinyl pentanoyl, 6- [(2, 3, 4, 5-) thiazolidinyl hexanoyl, 2, 2-dimethyl-3- [(2, 3, 5) thiazolidinyl propionyl] , 2-methyl-3- [(2, 3, 5) thiazolidinyl propionyl, [2,4-dioxo- (3, 5-) thiazolidinyl acetyl, 3- [2-oxo- (3, 4 or 5) thiazolidinyl] propionyl, 2- [4-oxo- (2,3-) thiazolidinyl-propionyl, 4- [5-oxo- (2,3-) 4-thiazolidinyl butyryl, 5- [2, 5-dioxo- (3-4-) thiazolidinyl pentanoyl, 6- [2, 4, 5-trioxo-3-thiazolidinyl] hexanoyl, 2- [4,5-dioxo- (2 or 3) thiazolidinyl acetyl, 2,2-dimethyl-3- [2, - dioxo- (3 or 5-) thiazolidinyl propionyl, 2-methyl-3- [2, 4-dioxo- (3 or 5) t iazolidinyl propionyl, 2- [4-oxo-2-isopropylidenehydrazono- (3 or 5-) thiazolidinyl] acetyl, 2- [2-oxo-5-isopropylidenehydrazono- (3 or 4) thiazolidinyl] acetyl, 2- [2,4-di (isopropylidenehydrazono) - (3 or 5) thiazolidinyl] acetyl 3- [2-methylidenehydrazono- (3, 4 or 5) thiazolidinyl] propionyl, 2- [4-ethylidenehydrazono- (2, 3 or 5) thiazolidinyl] propionyl, 4- [5-propylidenehydrazono- (2, 3 or 4-) thiazolidinyl] butyryl, 5- [2,5-di (isopropylidenehydrazono) - (3 or 4) thiazolidinyl] pentanoyl, 6- [2,4,5-tri (isopropylidenehydrazono) -3-thiazolidinyl] hexanoyl, 2- [4,5-di (isopropylidenehydrazono) - (2 or 3) thiazolidinyl] acetyl, 2,2-dimethyl-3- [4-butylidenehydrazono (2,3- or 5-) thiazolidinyl] propionyl, 2-methyl- 3- [5-pentylidene- (2, 3 or 4) thiazolidinyl] propionyl, and 2- (hexylidenehydrazono) - (3, 4 or 5) thiazolidinyl acetyl. Examples of the lower alkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a halogen atom include, in addition to the lower alkyl groups described above, linear or branched alkyl groups having 1 to 6 carbon atoms which they may have 1 to 3 substituents selected from the group consisting of a hydroxy group and a halogen atom such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1, -dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4, 4, 4- trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-phenylpropyl, 5-bromohexyl, 5,6-dibromohexyl, 2-hydroxy-3-fluoropropyl, and 2,2-dichloro-3-hydroxybutyl. Examples of the carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group include carbamoyl groups which may have 1 or 2 groups selected from the group consisting of a linear or branched alkyl group which has 1 to 6 carbon atoms and which has a linear or branched alkoxy group having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms such as carbamoyl groups, N- (2- methoxyethyl) carbamoyl, methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, tert-butylcarbamoyl, pentylcarbamoyl, hexylcarbaraoyl, dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, dibutylcarbamoyl, dipentylcarbamoyl, dihexylcarbamoyl, N-methyl-N-ethylcarbamoyl, N-ethyl-N-propylcarbamoyl, N-methyl-N-butylcarbamoyl, N-methyl-N-hexylcarbamoyl, N- (methoxymethyl) carbamoyl, N- (3-propoxypropyl) carbamoyl, N- (4-buto) xibutyl) carbamoyl, N- (4-ethoxybutyl) carbamoyl, N- (5- pentyloxypentyl) carbamoyl, N- (5-methox-pentyl) carbamoyl, N- (6-hex? Lox? Hex?) Carbamoyl, di (2-methox? Et? L) carbamoyl, N- (2-ethoxyethyl) -N -methylcarbamoyl, and N- (2-methox? et? l) -N-ethylcarbamoyl. Examples of the phenyl group which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a carbamoyl group which can have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group include phenyl which can be substituted in the phenyl ring with 1 to 3 groups selected from the group consisting of a carbamoyl group which can have 1 or 2 groups selected from the group consisting of an alkoxyalkyl group whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms and one group linear or branched alkyl having 1 to 6 carbon atoms; a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms; a carboxy group; a cyano group; a phenyl group; a halogen atom; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a benzoyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring; a phenylalkyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring and which alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms, and a hydroxyl group such as phenyl groups, 2- methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,3-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3- ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl , 3, 4, 5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4- trifluoromethoxyphenyl, 2- (bromomethoxy) phenyl, 3- (2-chloroethoxy) phenyl, 4- (2,3-dichloropropoxy) phenyl, 4- (4-fluorobutoxy) phenyl, 3- (5-chloropentyloxy) phenyl, 4- ( 5-bromohexyloxy) phenyl, 4- (5,6-dibromohexyloxy) phenyl, 3,4-di (trifluoromethoxy) phenyl, 3,4-di (4,4,4-trichlorobutoxy) phenyl, 2,4-di ( 3-chloro-2-methoxypropyl) phenyl, 2,5-di (3-chloropropoxy) phenyl, 2,6-di (2,2,2-trifluoroethoxy) phenyl, 3,4,5-tri (trifluoromethoxy) phenyl, 4- (2,2,2-trichloroethoxy) phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, -trifluoromethylphenyl, 4-trifluoromethylphenyl, 2- (bromomethyl) phenyl, 3- (2-chloroethyl) phenyl, 4- (2,3-dichloropropyl) phenyl, 4- (4-fluorobutyl) phenyl, 3- (5-chloropentyl) phenyl, 4- (5-bromohexyl) phenyl, 4- (5,6-dibromohexyl) phenyl, 3,4-di (trifluoromethyl) phenyl, 3,4-di (4,4,4-trichlorobutyl) phenyl, 2, 4-di (3-chloro-2-methylprop il) phenyl, 2,5-di (3-chloropropyl) phenyl, 2,6-di (2,2,2-trifluoroethyl) phenyl, 3,4,5-tri (trifluoromethyl) phenyl, 4- (2, 2) , 2-trichloroethyl) phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl, 2-methoxycarbonylphenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 2-ethoxycarbonylphenyl, 3-ethoxycarbonylphenyl, 4-ethoxycarbonylphenyl, 4-isopropoxycarbonylphenyl , 3-butoxycarbonylphenyl, 4-tert-butoxycarbonylphenyl, 4- pentyloxycarbonylphenyl, 4-hexyloxycarbonylphenyl, 3,4-dimethoxycarbonylphenyl, 3,4-diethoxycarbonylphenyl, 2,4-dimethoxycarbonylphenyl, 2,5-diethoxycarbonylphenyl, 2,6-dimethoxycarbonylphenyl, 3,, 5-triethoxycarbonylphenyl, 2-cyanophenyl, 3-cyanophenyl , 4-cyanophenyl, 3,4-dicyanophenyl, 3,5-dicyanophenyl, 2,4-dicyanophenyl, 2,5-dicyanophenyl, 2,6-dicyanophenyl, 3,4,5-tricyclophenyl, 2-phenylphenyl, 3-phenylphenyl , 4-phenylphenyl, 3,4-diphenylphenyl, 3,5-diphenylphenyl, 2-diphenylphenyl, 2,5-diphenylphenyl, 2,6-diphenylphenyl, 3,4,5-triphenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2- fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,4,6-trifluorophenyl, 2- bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3,4-dihydroxyphenyl, 3, 5-dihydroxyphenyl, 2,4-dihydroxyphenyl, 2, 5- dihydroxyphenyl, 2,6-dihydroxyphenyl, 3,4,5-trihydroxyphenyl, 3-benzylphenyl, 2- (2-phenylethyl) phenyl, 4- (l-phenylethyl) phenyl, 2- (3-phenylpropyl) phenyl, 3- ( 4-phenylbutyl) phenyl, 4- (5-phenylpentyl) phenyl, 2- (6-phenylhexyl) phenyl, 4- (1,1-diraethyl-2-phenylethyl) phenyl, 3- (2- methyl-3-phenylpropyl) phenyl, 2- (4-fluorobenzyl) phenyl, 2-methyl-5-chlorophenyl, 2-methoxy-5-chlorophenyl, 4- (4-fluorobenzoyl) phenyl, 4- (4-fluorobenzyl) phenyl , 3- (2-chlorobenzyl) phenyl, 4- (3-chlorobenzyl) phenyl, 2- (4-chlorobenzyl) phenyl, 3- [2- (4-fluorophenyl) ethyl] phenyl, 4- [2- (4- chlorophenyl) ethyl] phenyl, 2- (3,4-dibromobenzyl) phenyl, 3- (3,4-diiodobenzyl) phenyl, 4- (2,4-difluorobenzyl) phenyl, 2- (2,5-dichlorobenzyl) phenyl, 3- (2,6-dichlorobenzyl) phenyl, 4- (3,4,5-trifluorobenzyl) phenyl, 2- [3- (4-chlorophenyl) propyl] phenyl, 3- [l- (2-bromophenyl) ethyl] phenyl, 4- [4- (3-fluorophenyl) butyl] phenyl, 2- [5- (4-iodophenyl) pentyl] phenyl, 3- [6- (4-chlorophenyl) hexyl] phenyl, 2- [1, -dimethyl-2- (3-fluorophenyl) ethyl] phenyl, 4- [2-methyl-3- (4-chlorophenyl) propyl] phenyl, 2,4-dibenzylphenyl, 2,4,6-tribenzylphenyl, 2-chloro- 4-cyanophenyl, 3-hydroxy-4-phenylphenyl, 3-ethoxycarbonyl-2-benzoylphenyl, 2-benzyl-4-methyl-6-methoxyphenyl, 4- [(2-methoxyethyl) carbamoyl] phenyl, 3- ( N-ethyl-N-isopropylcarbaraoyl) phenyl, 4-dimethylcarbaraoylphenyl, 2-carboxyphenyl, 3-carboxyphenyl, and 4-carboxyphenyl. Examples of the phenyl group having a lower alkylenedioxy group as a substituent on the phenyl ring include phenyl groups having a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring such as groups 3, 4- methylenedioxyphenyl, 3,4-trimethylenedioxyphenyl, 2,3- ethylenedioxyphenyl, 2,3-tetramethylenedioxyphenyl, 2,3-methylenedioxyphenyl, 3, -ethylenedioxyphenyl, and 2,3-trimethylenedioxyphenyl. Examples of the naphthyl lower alkyl group include naphthylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1 or 2-) naphthylmethyl, 2 - [(1 or 2) naphthyl] ethyl groups , 1 - [(1 or 2-) naphthyl] ethyl, 3 - [(1 or 2-) naphthyl] propyl, 4 - [(1 or 2) -naphthyl] -butyl, 5 - [(1 or 2) -naphthyl] ] pentyl, 6 - [(1 or 2-) naphthyl] hexyl, 1, 1-dimethyl-2- [(1 or 2-) naphthyl] ethyl, and 2-methyl-3 - [(1 or 2) -naphthyl] ] propyl. Examples of the phenoxy group which can be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent include phenoxy groups which may be substituted on the phenyl group with 1 to 3 groups selected from the group consisting of a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms, which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as phenoxy, 2-methylphenoxy, 3- groups methylphenyl, 4-methylphenoxy, 2-ethylphenoxy, 3- ethylphenoxy, 4-ethylphenoxy, 4-isopropylphenoxy, 3-butylphenoxy, 4-pentylphenoxy, 4-hexylphenoxy, 3, -dimethylphenoxy, 3,4-diethylphenoxy, 2,4-dimethylphenoxy, 2,5-dimethylphenoxy, 2,6-dimethylphenoxy , 3, 4, 5-trimethylphenoxy, 2-methoxyphenoxy, 3-methoxyphenoxy, 4-methoxyphenoxy, 2-ethoxyphenoxy, 3-ethoxyphenoxy, 4-ethoxyphenoxy, 4-isopropoxyphenoxy, 3-butoxyphenoxy, 4-pentyloxy-phenoxy, 4-hexyloxyphenoxy, 3 , 4-dimethoxyphenoxy, 3,4-diethoxyphenoxy, 2,4-dimethoxyphenoxy, 2,5-dimethoxyphenoxy, 2,6-dimethoxyphenoxy, 3,4,5-trimethoxyphenoxy, 2-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 2 - (bromomethoxy) phenoxy, 3- (2-chloroethoxy) phenoxy, 4- (2,3-dichloropropoxy) phenoxy, 4- (4-fluorobutoxy) phenoxy, 3- (5-chloropentyloxy) phenoxy, 4- (5-bromohexyloxy) ) phenoxy, 4- (5,6-dibromohexyloxy) phenoxy, 3,4-di (trifluoromethoxy) phenoxy, 3,4-di (4, 4, 4-trichlorobutoxy) phenoxy, 2, -di (3-chloro-2) -methoxypropyl) phenoxy, 2,5-di (3-chloropropoxy) phenoxy, 2,6-di (2,2,2-trifluoroethoxy) phenoxy, 3, 4, 5-tri (trifl) uoromethoxy) phenoxy, 4- (2, 2, 2-trichloroethoxy) phenoxy, 2-methyl-4-trifluoromethoxyphenoxy, 3-ethyl-4-trichloromethoxyphenoxy, 2-methoxy-4-trifluoromethoxyphenoxy, 3-ethoxy-4-trichloromethoxyphenoxy, 2 -trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 4-trifluoromethylphenoxy, 2- (bromomethyl) phenoxy, 3- (2-chloroethyl) phenoxy, 4- (2,3-dichloropropyl) phenoxy, 4- (-fluorobutyl) phenoxy, 3- (5 -chloropentyl) phenoxy, 4- (5-bromohexyl) phenoxy, 4- (5, 6- dibromohexyl) phenoxy, 3,4-di (trifluoromethyl) phenoxy, 3,4-di (4, 4, 4-trichlorobutyl) phenoxy, 2,4-di (3-chloro-2-methylpropyl) phenoxy, 2, 5- di (3-chloropropyl) phenoxy, 2,6-di (2,2,2-trifluoroethyl) phenoxy, 3,4,5-tri (trifluoromethyl) phenoxy, 4- (2,2,2-trichloroethyl) phenoxy), -methyl-4-trifluoromethylphenoxy, 3-ethyl-4-trichloromethylphenoxy, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 3-dicyanophenoxy, 3, 5-dicyanophenoxy, 2,3-dicyanophenoxy, 2,4-dicyanophenoxy, 2, 5-dicyanophenoxy, 2,6-dicyanophenoxy, 3, 4, 5-tricianofenoxi, 2-cyano-4-methylphenoxy, 3-cyano-4-methoxyphenoxy, 3-cyano-5-trifluoromethylphenoxy, and 4-cyano-3 -trifluoromethoxyphenoxy. Examples of the phenyl lower alkoxy group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and an alkoxy group lower which may have a halogen atom as a substituent include, in addition to the lower alkoxy phenyl groups described above, phenylalkoxy groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 6 carbon atoms which may have 1 to 3 carbon atoms halogen-corao substituents, and whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms such as 2,5-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 3,5-difluorobenzyloxy groups, 2,6-difluorobenzyloxy, 3-trifluoromethylbenzyloxy, 2-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 3,4-dimethoxybenzyloxy, 3,5-dimethoxybenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-methylbenzyloxy, 3-methylbenzyloxy, 4-Rethylbenzyloxy, 3,4-dimethylbenzyloxy, 2,3-dimethylbenzyloxy, 2-methoxybenzyloxy, 3-methoxybenzyloxy, 4-methoxybenzyloxy, 2,3-dichlorobenzyloxy, 2,4-dichlorobenzyloxy, 2,5-dichlorobenzyloxy, 3-dichlorobenzyloxy , 2,6-dichlorobenzyloxy, 4-fluorobenzyloxy, 3-fluorobenzyloxy, 2-fluorobenzyloxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 2-trifluoromethoxybenzyloxy, 4-tert-butylbenzyloxy, 4-ethylbenzyloxy, 4-isopropylbenzyloxy, 4-methoxy-3 -chlorobenzyloxy, 2- (4-methoxyphenyl) ethoxy, 2- (4-fluorophenyl) etho xi, 2- (4-chlorophenyl) ethoxy, 2- (3-methoxyphenyl) ethoxy, 2- (4-methylphenyl) ethoxy, 3-methyl-4-chlorobenzyloxy, 4- (4-methoxyphenyl) butoxy, 2- (4 -methylphenyl) ethoxy, 4-tert-butylocybenzyloxy, 3-chloro-6-methoxybenzyloxy, 4-methoxy-3-methylbenzyloxy, 2- (2-fluorophenyl) ethoxy, 1- (3-bromophenyl) ethoxy, 3- (4- iodophenyl) propoxy, 4- (2-bromophenyl) butoxy, 5- (3- chlorophenyl) pentyloxy, 6- (4-bromophenyl) hexyloxy, 1, l-dimethyl-2- (2, -dichlorophenyl) ethoxy, 2-methyl-3- (2,4,6-trifluorophenyl) propoxy, 2- (2 -ethylphenyl) ethoxy, 1- (3-propylphenyl) ethoxy, 3- (4-butylphenyl) propoxy, 4- (2-pentylphenyl) butoxy, 5- (3-hexylphenyl) pentyloxy, 6- (4-trifluoromethylphenyl) hexyloxy, 1, 1-dimethyl-2- (2,4-dimethylphenyl) ethoxy, 2-methyl-3- [2,4,6-tri (trifluororaethyl) phenyl] propoxy, 2- (2-ethoxyphenyl) ethoxy, 1- ( 3-propoxyphenyl) ethoxy, 3- (4-butoxyphenyl) propoxy, 4- (2-pentyloxyphenyl) butoxy, 5- (3-hexyloxyphenyl) pentyloxy, 6- (4-trifluoromethoxyphenyl) hexyloxy, 1, 1-dimethyl-2- (2,4-dimethoxyphenyl) ethoxy, and 2-methyl-3- [2,4,6-tri (trifluoromethoxy) phenyl] propoxy. Examples of the lower alkyl group substituted with 1,2,3-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring include alkyl groups substituted with 1, 2, 3 , 4-tetrahydronaphthyl which may have 1 to 5 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the 1,2,3,4-tetrahydronaphthalene ring, and whose alkyl portion is a linear alkyl group or branched having 1 to 6 carbon atoms such as (1, 2, 5 or 6-) 1,2, 3,4-tetrahydronaphthylmethyl, 2 - [(1, 2, 5 or 6) 1, 2,3 groups , 4-tetrahydronaphthyl] ethyl, 1 - [(1, 2, 5 or 6-) l, 2,3,4- tetrahydronaphthyl ethyl, 3 - [(1, 2, 5 or 6-) l, 2,3,4-tetrahydronaphthyl propyl, 4 - [(1, 2, 5 or 6-) l, 2,3,4-tetrahydronaphthyl butyl , 5 - [(1, 2, 5 or 6-) l, 2,3,4-tetrahydronaphthyl pentyl, 6 - [(1, 2, 5 or 6-) l, 2,3,4-tetrahydronaphthyl hexyl, 1 , l-dimethyl-2- [(1, 2, 5 or 6-) l, 2,3,4-tetrahydronaphthyl ethyl, 2-methyl-3- [(1, 2, 5 or 6-) l, 2, 3,4-tetrahydronaphthyl propyl, 1,1,4,4-tetramethyl (2, 3, 5 or 6-) 1, 2, 3, -tetrahydronaphthylmethyl, 1, 1,4,4,5-pentamethyl (2, 3) , 6, 7 or 8-) 1,2,3,4-tetrahydronaphthylmethyl, 1,4-, 4-trimethyl (2, 3, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydronaphthylmethyl, 5,6- dimethyl (2, 3, 7 or 8-) 1, 2, 3, 4-tetrahydronaphthylmethyl, 2- [1-methyl- (1, 2, 3, 4, , 6, 7 or 8-) 1, 2,3,4-tetrahydronaphthyl] ethyl, 1- [2-ethyl- (1, 2, 3, 4, 5, 6, 7 or 8-) 1,2, 3, 4-tetrahydronaphthyl] ethyl, 3- [3-propyl- (1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydronaphthyl] propyl, 4- [(4 -butyl- (1, 2, 3, 4, 5, 6, 7 or 8-) l, 2,3,4-tetrahydronaphthyl] butyl, 5- [5-pentyl- (1, 2, 3, 4, 6, 7 or 8-) 1, 2, 3, 4-tetrahydronaphthyl] pentyl, 6- [6-hexyl- (1, 2, 3, 4, 5, 7 or 8-) 1, 2, 3, 4- tetrahydronaphthyl] hexyl, 1,1-dimethyl-2- [1,7-dimethyl- (1, 2, 3, 4, 5, 6 or 8-) 1, 2,3,4-tetrahydronaphthyl] ethyl, and 2- methyl-3- [1,1-trimethyl- (2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydronaphthyl] propyl. Examples of the piperidinyl group which may have 1 to 3 lower alkyl groups as substituents on the piperidine ring include piperidinyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperidine ring such as (1, 2, 3 or 4-) piperidinyl, 1-ethyl- (2, 3 or 4-) piperidinyl, 1-ethyl- (2, 3 or 4-) piperidinyl, l-propyl- (2, 3 or 4-) piperidinyl, 1-isopropyl- (2, 3 or 4-) piperidinyl, l-butyl- (2, 3 or 4-) piperidinyl, 1-isobutyl - (2, 3 or 4-) piperidinyl, 1-tert-butyl- (2, 3 or 4) piperidinyl, 1-pentyl- (2, 3 or 4-) piperidinyl, l-hexyl- (2, 3 or 4-) piperidinyl, 1,2-dimethyl- (3, 4, 5 or 6-) piperidinyl, and 1, 2, 6-trimethyl- (3, 4 or 5-) piperidinyl. Examples of the quinolyl lower alkyl group include quinolyalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4, 5, 6, 7 or 8-) quinolyl-methyl groups , 2 - [(2, 3, 4, 5, 6, 7 or 8-) quinolyl] ethyl, l - [(2, 3, 4, 5, 6, 7 or 8-) quinolyl] ethyl, 3- [ (2, 3, 4, 5, 6, 7 or 8-) quinolyl] propyl, 4 - [(2, 3, 4, 5, 6, 7 or 8-) quinolyl] butyl, 5 - [(2, 3 , 4, 5, 6, 7 or 8-) pentyl, and 6 - [(2, 3, 4, 5, 6, 7 or 8-) hexyl. Examples of the 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group include groups 1, 2, 3, 4-tetrazolylalkyl whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have, in the tetrazole ring, a substituent selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and an alkyl phenyl group whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms, such as groups [ (1 or 5-) 1, 2, 3, 4-tetrazolyl] methyl, 2 - [(1 or 5) 1,2, 3,4-tetrazolyl] ethyl, 1 - [(1 or 5) 1, 2,3,4-tetrazolyl] ethyl, 3 - [(1 or 5-) 1, 2, 3, 4-tetrazolyl] propyl, 4 - [(1 or 5) 1,2, 3,4-tetrazolyl] butyl, 5 - [(l or 5-) l, 2,3,4-tetrazolyl] pentyl, 6 - [(l or 5-) 1, 2, 3, 4-tetrazolyl] hexyl, 5- [l-methyl] -5- (1,2, 3, 4-tetrazolyl)] pentyl, 6- [l-methyl-5- (1,2, 3,4-tetrazolyl)] hexyl, 5-methyl-1- (1,2 , 3,4-tetrazolyl) methyl, 2- [5-ethyl-l- (1, 2,3,4-tetrazolyl] hexyl, 1, 1-dimethyl-2- [(1 or 5-) 1, 2, 3,4-tetrazolyl)] ethyl, 2-methyl-3 - [(1 or 5-) 1, 2,3,4-tetrazolyl] propyl, [1-methyl-5- (1, 2, 3, 4 tetrazolyl)] methyl, [l-ethyl-5- (1, 2, 3, 4-tetrazolyl)] methyl, 2- [1-propyl-5- (1,2,3,4-tetrazolyl)] ethyl, 1 - [1-buti1-5 - (1,2,3,4-tetrazolyl)] ethyl, 3- [l-pentyl-5- (1, 2,3,4-tetrazolyl)] propyl, 3- [5-propyl-1- (1,2,3,4-tetrazolyl)] propyl, 4- [5-butyl-1- (1,2,3,4-tetrazolyl)] butyl, 5- [ 5-pentyl-1- (1,2,3,4-tetrazolyl)] pentyl, 6- [5-hexyl-1- (1,2,3,4-tetrazolyl)] hexyl, [l-ethyl-5- (1,2,3,4-tetrazolyl)] methyl, [l-benzyl-5- (1,2,3,4-tetrazolyl)] methyl, 1- [(2-phenylethyl) -5- (l, 2 , 3,4-tetrazolyl)] methyl, 2- [1- (3-phenylpropyl) -5- (1,2,3-tetrazolyl)] ethyl, 1- [1- (4-phenylbutyl) -5- ( 1,2, 3,4-tetrazolyl)] ethyl, 3- [1- (5-phenylpentyl) -5- (1, 2, 3, 4- tetrazolyl)] propyl, 4- [1- (6-phenylhexyl) -5- (1, 2,3,4-tetrazolyl)] butyl, 5- [1- (1, 1-diraethyl-2-phenylethyl) -5 - (1,2,3,4-tetrazolyl)] methyl, 6- [1- (2-methyl-3-phenylpropyl) -5- (1,2,4,4-tetrazolyl)] hexyl, 5-benzyl- l- (1, 2, 3, 4-tetrazolyl) methyl, 2- [5- (1-phenylethyl) -1- (1, 2, 3, 4-tetrazolyl)] ethyl, 3- [5- (3- phenylpropyl) -l- (1,2,3-tetrazolyl)] propyl, 4- [5- (4-phenylbutyl) -1- (1,2,3-tetrazolyl)] butyl, 5- [5- ( 5-phenylpentyl) -1- (1, 2, 3, 4-tetrazolyl)] pentyl, and 6- [5- (6-phenylhexyl) -l- (1, 2,3,4-tetrazolyl)] hexyl. Examples of the thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring include thiazolylalkyl groups which may have 1 or 2 phenyl groups as substituents on the thiazole ring and which alkyl portion is a linear alkyl group or branched having 1 to 6 carbon atoms such as [(2, 4 or 5) thiazolyl] methyl, 2 - [(2, 4 or 5) thiazolyl] ethyl, l - [(2, 4 or 5- ) thiazolyl] ethyl, 3 - [(2, 4 or 5) thiazolyl] propyl, 4 - [(2, 4 or 5) thiazolyl] butyl, 5 - [(2, 4 or 5) thiazolyl] pentyl, 6 - [(2, 4 or 5-) thiazolyl] hexyl, 1,1-dimethyl-2- [(2, 4 or 5) thiazolyl] ethyl, 2-methyl-3- [(2, 4 or 5- ) thiazolyl] propyl, [2-phenyl- (4 or 5) thiazolyl] methyl, 2- [4-phenyl- (2 or 5) thiazolyl] ethyl, 1- [5-phenyl- (2 or 4-) thiazolyl] ethyl, 3- [2-phenyl- (2 or 5-) thiazolyl] propyl, 4- (2,4-diphenyl-5-thiazolyl) butyl, 5- (2,5-diphenyl-4-thiazolyl) pentyl , 6- (, 5-diphenyl-2-thiazolyl) hexyl, 1, l-dimethyl-2- [2-phenyl- (4 or -) thiazolyl] ethyl, 2-methyl-3- [4-phenyl- (2 or 5) thiazolyl] propyl, [4-phenyl- (2 or 5) thiazolyl] methyl, [5-phenyl- (2 or 4-) thiazolyl] methyl, (2, 4-diphenyl-5-thiazolyl) methyl, (2,5-diphenyl-4-thiazolyl) methyl, and (4,5-diphenyl-2-thiazolyl) methyl. Examples of the benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom include benzoylalkyl groups which may have, on the phenyl ring, 3 substituents selected from the group consisting of a linear or branched alkoxy group having 6 carbon atoms and a halogen atom and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as benzoylmethyl groups, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoilpentilo, 6-benzoilhexilo, 1, l-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, 4-fluorobenzoilmetilo, 2-clorobenzoilmetilo, 3-clorobenzoilmetilo, 4-clorobenzoilmetilo, 2- (4-fluorobenzoyl) ethyl, 2- (4-chlorobenzoyl) ethyl, 3, 4-dibroraobenzoilmetilo, 3,4-diyodobenzoilmetilo, 2, 4-difluorobenzoilmetilo, 2,5-diclorobenzoilmetilo, 2, 6-dichlorobenzoylmethyl, 3, 4,5-trifluorobenzoylmethyl, 3- (4-chlorobenzoyl) propyl, 1- (2-bromobenzoyl) ethyl, 4- (3-fluorobenzoyl) butyl, 5- (4-iodobenzoyl) pentyl, 6- (4-chlorobenzoyl) hexyl , 1, l-dimethyl-2- (3-fluorobenzoyl) ethyl, 2-methyl-3- (4-chlorobenzoyl) propyl, 2-metoxibenzoilmetilo, 2- (3-methoxybenzoyl) ethyl, 2- (4-methoxybenzoyl) ethyl, 4-metoxibenzoilmetilo, l- (2 -ethoxybenzoyl) ethyl, 3- (3-ethoxybenzoyl) propyl, 4- (4-ethoxybenzoyl) butyl, 5- (4-isopropoxybenzoyl) pentyl, 6- (3-butoxybenzoyl) hexyl, 1, 1-dimethyl-2- ( 4-pentiloxibenzoil) ethyl, 2-meti1-3- (4-hexiloxibenzoil) propyl, 3,4-dimetoxibenzoilmetilo, 3, 4-dietoxibenzoilmetilo, 2,4-dimetoxibenzoilmetilo, 2, 5-dimetoxibenzoilmetilo, 2,6-dimetoxibenzoilmetilo, 3 , 4,5-trimethoxybenzoylmethyl, 2-chloro-4-methoxybenzoylmethyl, and 3-fluoro-5-ethoxybenzoylmethyl. Examples of the piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring include piperidinylalkyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the ring of piperidine and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2, 3 or 4-) piperidinyl] methyl groups, 2 - [(1, 2, 3 or 4) -) piperidinyl] ethyl, 1- [(1, 2, 3 or 4-) piperidinyl] ethyl, 3 - [(1, 2, 3 or 4-) piperidinyl] propyl, 4 - [(1, 2, 3 or 4-) piperidinyl] butyl, 5- [(1, 2, 3 or 4-) piperidinyl] pentyl, 6 - [(1, 2, 3 or 4-) piperidinyl] hexyl, 1, 1-dimethyl-2- [ (1, 2, 3 or 4-) piperidinyl] ethyl, 2-methyl-3- [(1, 2, 3 or 4- ) piperidinyl] propyl, [1-methyl- (2, 3 or 4-) piperidinyl] methyl, 2- [1-ethyl- (2, 3 or 4-) piperidinyl] ethyl, 1- [4-propyl- (1 , 2 or 3-) piperidinyl ethyl, 3- [3-isopropyl- (1, 2, or 6-) piperidinyl propyl, 4- [2-butyl- (1, 3, 4, 5 or 6-) piperidinyl butyl, 5- [1-isobutyl- (2, 3 or 4-) piperidinyl pentyl, 6- [1-tert-butyl- (2, 3 or 4-) piperidinyl hexyl, 1, l-dimethyl-2- [4-pentyl] - (1, 2 or 3-) piperidinyl ethyl, 2-methyl-3- [1-hexyl- (2, 3 or 4-) piperidinyl propyl, [1,2-dimethyl- (3, 4, 5 or 6- ) piperidinyl methyl, and [1, 2, 6-trimethyl- (3, 4 or 5-) piperidinyl methyl. Examples of the imidazolyl group which may have 1 to 3 phenyl groups as substituents on the imidazole ring include imidazolyl groups which may have 1 to 3 phenyl groups as substituents on the imidazole ring such as groups (1, 2, 4 or 5) ) imidazolyl, l-phenyl- (2, 4 or 5) imidazolyl, 2-phenyl- (1, 4 or 5) imidazolyl, 4-phenyl- (1, 2 or 5) imidazolyl, 5-phenyl- ( 1, 2 or 4) imidazolyl, 1,2-diphenyl- (4 or 5) imidazolyl, 2,4-diphenyl- (1 or 5) imidazolyl, 4,5-diphenyl- (1 or 2) imidazolyl , 2, 5-diphenyl- (1 or 4-) imidazolyl, and 2,4,5,5-triphenyl-1-imidazolyl. Examples of the benzimidazolyl group which may have 1 to 3 lower alkyl groups as substituents on the benzimidazole ring include benzimidazolyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the benzimidazole ring such as (1, 2, 4, 5, 6 or 7-) benzimidazolyl, l-methyl- (2, 4, 5, 6 or 7-) benzimidazolyl groups, -ethyl- (1, 4, 5, 6 or 7) benzimidazolyl, 4-propyl- (1, 2, 5, 6 or 7) benzimidazolyl, 5-butyl- (1, 2, 4, 6 or 7) ) benzimidazolyl, 6-pentyl- (1, 2, 4, 5 or 7) benzimidazolyl, 7-hexyl- (1, 2, 4, 5 or 6) benzimidazolyl, l-ethyl- (2, 4, 5, 6 or 7-) benzimidazolyl] hexyl, l-butyl- (2, 4, 5, 6 or 7) benzimidazolyl, 1-isopropyl- (1, 2, 4, 5, 6 or 7) benzimidazolyl, 1, 2 -dimethyl- (4, 5, 6 or 7-) benzimidazolyl, l-methyl-4-ethyl- (2, 5, 6 or 7) benzimidazolyl, l-propyl-5-methyl- (2, 4, 6 or 7-) benziraidazolyl, and 1, 2, 5-trimethyl- (2, 4, 5, 6 or 7-) enimidazolyl. Examples of the pyridyl lower alkoxy group include pyridylalkoxy groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3 or 4) pyridylmethoxy groups, 2 - [(2, 3 or 4- ) pyridyl] ethoxy, l - [(2, 3 or 4) pyridyl] ethoxy, 3 - [(2, 3 or 4) pyridyl] propoxy, 4 - [(2, 3 or 4) pyridyl] butoxy, ll-dimethyl-2- [(2, 3 or 4) pyridyl] ethoxy, 5 - [(2, 3 or 4) pyridyl] pentyloxy, 6- [(2, 3 or 4) pyridyl] hexyloxy, l - [(2, 3 or 4) pyridyl] isopropoxy, and 2-methyl-3- [(2, 3 or 4) pyridyl] propoxy. Examples of the 1, 2, 3, 4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include groups 1, 2, 3, 4-tetrahydroquinolyl-alkyl which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as groups (1 , 2, 3, 4, 5, 6, 7 or 8-) l, 2,3,4-tetrahydroquinolylmethyl, 2 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1,2 , 3,4-tetrahydroquinolyl] ethyl, 1 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1,2,3,4-tetrahydroquinolyl] ethyl, 3 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] propyl, 4 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] butyl, 5 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, -tetrahydroquinolyl] pentyl, 6 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] hexyl, 1, l-dimethyl-2 - [(1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] ethyl, 2-methyl-3- [(1, 2, 3, 4, 5, 6, 7 or 8-) l, 2,3,4-tetrahydroquinolyl] propyl, [ 2-oxo- (1, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] methyl, [4-oxo- (1, 2, 3, 5, 6, 7 u 8-) 1, 2, 3 , 4-tetrahydroquinolyl] methyl, [2, 4-dioxo- (1, 3, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] methyl, 2- [2-oxo- (l, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] ethyl, 3- [4-oxo- (1, 2, 3, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] propyl, 4- [2,4-dioxo- (1, 3, 5, 6, 7 'or 8-) 1, 2, 3, 4-tetrahydroquinolyl] butyl, 5- [2 -oxo- (1, 3, 4, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydroquinolyl] pentyl, and 6- [4-oxo- (1, 2, 3, 5, 6, 7 or 8-) 1,2, 3, 4-tetrahydroquinolyl] hexyl. Examples of group 1, 3, -oxadiazolyl alkyl lower which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring include 1,3,4-oxadiazolylalkyl groups which may have an oxo group as a substituent on the 1,3-oxadiazole ring and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2 or 5-) 1,3,4-oxadiazolyl-ethyl, 2 - [(2 or 5-) 1, 3, 4- oxadiazolyl] ethyl, l - [(2 or 5-) 1, 3,4-oxadiazolyl] ethyl, 3- [(2 or 5-) l, 3,4-oxadiazolyl] propyl, 4 - [(2 or 5- ) 1, 3, 4-oxadiazolyl] butyl, 5 - [(2 or 5-) 1, 3, 4-oxadiazolyl] pentyl, 6 - [(2 or 5-) l, 3,4-oxadiazolyl] hexyl, 1 , l-dimethyl-2- [(2 or 5-) l, 3,4-oxadiazolyl] ethyl, 2-methyl-3- [(2 or 5-) l, 3,4-oxadiazolyl] propyl, 2-oxo - [(3 or 5-) 1, 3, 4-oxadiazolyl] methyl, 5-oxo - [(2 or 3-) 1, 3, 4-oxadiazolyl] methyl, 2- [2-oxo- (3 or 5 -) (1,3,4-oxadiazolyl)] ethyl, l- [5-oxo- (2 or 3-) l, 3,4-oxadiazolyl] ethyl, 3 - [(2 or 5-) 1, 3, 4-Oxadiazolyl] propyl, 4- [2-oxo (3 or 5-) 1, 3, 4-oxadiazolyl] butyl lo, 5- [5-oxo (2 or 3-) l, 3,4-oxadiazolyl] pentyl, 6- [2-oxo (3 or 5-) 1,3,4-oxadiazolyl] hexyl, 1, l- dimethyl-2- [5-oxo (2 or 3-) 1, 3, 4-oxadiazolyl] ethyl, and 2-methyl-3- [2-oxo (3 or 5-) 1, 3, 4-oxadiazolyl] propyl . Examples of the thienyl lower alkyl group include thienylalkyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2 or 3) thienylmethyl, 2 - [(2 or 3) thienyl] ethyl groups , l - [(2 or 3-) thienyl] ethyl, 3 - [(2 or 3) thienyl] propyl, 4 - [(2 or 3- ) thienyl] butyl, 5 - [(2 or 3) thienyl] pentyl, 6 - [(2 or 3) thienyl] hexyl, 1, l-dimethyl-2- [(2 or 3) thienyl] ethyl, and 2-methyl-3 - [(2 or 3) thienyl] propyl. Examples of the pyrimidinylcarbonyl groups that may have an oxo group as a substituent on the pyrimidine ring include pyrimidinylcarbonyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring such as (2, 3, 4 or 6-) pyrimidinylcarbonyl , 2,6-dioxo- (1, 3, 4 or 5) pyrimidinylcarbonyl, 2-oxo- (1, 3, 4, 5 or 6) pyrimidinylcarbonyl, 6-oxo- (1, 2, 3, 4 or 5-) pyrimidinylcarbonyl, 4-oxo- (1, 2, 3, 5 or 6) pyrimidinylcarbonyl, 2,4-dioxo- (1, 3, 4 or 6) pyrimidinylcarbonyl, and 2, 4, 6-trioxo- (1, 3 or 5-) pyrimidinylcarbonyl. Examples of the lower alkoxy lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have a straight or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as methoxymethoxy, 1-ethoxyethoxy groups, 2-methoxyethoxy, 2-propoxyethoxy, 3-isopropoxypropoxy, 4-butoxybutoxy, 5-pentyloxypentyloxy, 6-hexyloxyhexyloxy, 1,1-dimethyl-2-methoxyethoxy, 2-methyl-3-ethoxypropoxy, and 3-methoxypropoxy. Examples of the lower alkoxycarbonyl lower alkoxy group include alkoxycarbonylalkoxy groups whose two alkoxy portions are linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxycarbonyl ethoxy, ethoxycarbonylmethoxy, 2-methoxycarbonylethoxy, 2-ethoxycarbonyl ethoxy, 1-ethoxycarbonyl ethoxy, 3-methoxycarbonylpropoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy groups , 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, and hexyloxycarbonylmethoxy. Examples of the carboxy lower alkoxy group include carboxyalkoxy groups whose alkoxy portion is a linear or branched alkoxy group having 1 to 6 carbon atoms such as carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, carboxypentyloxy, 6-carboxyhexyloxy, 1, l-dimethyl-2-carboxyethoxy, and 2-methyl-3-carboxypropoxy. Examples of the phenoxy lower alkanoyl group include phenoxyalkanoyl groups whose alkanoyl portion is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-phenoxyacetyl, 3-phenoxypropionyl, 2-phenoxypropionyl, 4-phenoxybutyryl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, 2,2-dimethyl-2-phenoxypropionyl, and 2-methyl-3-phenoxypropionyl. Examples of group 1,2,3,4- tetrahydroquinolylcarbonyl which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1, 2, 3, 4-tetrahydroquinolylcarbonyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring such as [(1, 3, 4, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] carbonyl, [2-oxo- (1, 3, 4, 5, 6, 7 or 8-) 1, 2, 3,4-tetrahydroquinolyl] carbonyl, [4-oxo- (1, 2, 3, 5, 6, 7 or 8-) 1, 2, 3, 4-tetrahydroquinolyl] carbonyl, and [2,4-dioxo- ( 1, 3, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydroquinolyl] carbonyl. Examples of the 1, 2, 3, 4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolyl groups which may have 1 or 2 oxo groups as substituents on the the tetrahydroquinoline ring such as groups (1, 2, 3, 4, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydroquinolyl, 2-oxo- (1, 3, 4, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydroquinolyl, 4-oxo- (1, 2, 3, 5, 6, 7 or 8-) 1,2, 3,4-tetrahydroquinolyl, and 2, -dioxo - (1, 3, 5, 6, 7 or 8-) 1, 2,3,4-tetrahydroquinolyl. Examples of the amino group which a lower alkoxycarbonyl group may have as a substituent include amino groups which may have a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms such as amino, methoxycarbonylamino, ethoxycarbonylamino groups, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, and hexyloxycarbonylamino. Examples of the benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring include benzoyl groups which may have 1 to 3 linear or branched alkoxy groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as benzoi groups, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoylchloride, 3-butoxybenzoyl, 4-pentiloxibenzoilo, 4-hexiloxibenzoilo, 3, -dimetoxibenzoilo, 3, 4-diethoxybenzoyl, 2,4-dimethoxybenzoyl, 2,5-diraetoxybenzoyl, 2,6-dimethoxybenzoyl, and 3,4,5-trimethoxybenzoyl. Examples of the lower alkyl group having 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, an atom of halogen, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group include, in addition to the lower alkyl phenyl groups described above, linear or branched alkyl groups having 1 to 6 carbon atoms and 1 to 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a group cyano, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkylthio group having 1 to 6 carbon atoms such as 1, 1-diphenylmethyl, 1, 1-di (4-) groups fluorophenyl) methyl, 1-phenyl-1- (4-methoxyphenyl) methyl, 3,3-diphenylpropyl, 2, 5-difluorobenzyl, 2, -difluorobencilo, 3,4-difluorobenzyl, 3, 5-difluorobenzyl, 2, 6- difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl , 3,5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 3, 4-dimethylbenzyl, 2, 3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl , 4-cyanobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-raetoxibencilo, 2, 3-dichlorobenzyl, 2, dichlorobenzyl, 2,5 dichlorobenzyl, 3-dichlorobenzyl, 2, 6-dichlorobenzyl, 4-fluorobenzyl, 3 -fluorobenzyl, 2-fluorobenzyl, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3- trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluoro-ethoxybenzyl, 4-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2- (4-ethoxyphenyl) ethyl, - (4-fluorophenyl) ethyl, 2- (4-chlorophenyl) ethyl, 2- (3-methoxyphenyl) ethyl, 2- (4-methylphenyl) ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4 -nitrobenzyl, 4- (4-methoxyphenyl) butyl, 2- (4-methylphenyl) ethyl, 4-tert-butyclocarbonylbenzyl, 3-chloro-6-methoxybenzyl, 4-nitro-3-methylbenzyl, 4-tert-butyrylbenzyl, 2 - (2-ethoxycarbonylphenyl) ethyl, 1- (3-propoxycarbonylphenyl) ethyl, 3- (4-pentyloxycarbonylphenyl) propyl, 4- (3-hexyloxycarbonylphenyl) butyl, 5- (3,4-dimethoxycarbonylphenyl) pentyl, 6- (3 , 4,5-diethoxycarbonylphenyl) hexyl, 1,1-dimethyl-2- (4-butoxycarbonylphenyl) ethyl, 2-methyl-3- (4-ethoxycarbonylphenyl) propyl, 2- (2-cyanophenyl) ethyl, 1- (3 -cyanophenyl) ethyl, 3- (4-cyanophenyl) propyl, 4- (2-cyanophenyl) butyl, 5- (3-cyanophenyl) pentyl, 6- (4-cyanophenyl) hexyl, 1, l-dimethyl-2- (2, -dicyanophenyl) ethyl, 2-methyl-3- (2,4,6-tricityophenyl) propyl, 2- (2-nitrophenyl) ethyl , 1- (3-nitrophenyl) ethyl, 3- (4-nitrophenyl) propyl, 4- (2-nitrophenyl) butyl, 5- (3-nitrophenyl) pentyl, 6- (4-nitrophenyl) hexyl, 1, 1- dimethyl-2- (2,4-dinitrophenyl) ethyl, 2- methy1-3- (2,4,6-trinitrophenyl) propyl, 2- (2-phenylphenyl) ethyl, 1- (3-phenylphenyl) ethyl, 3- (4-phenylphenyl) propyl, 4- (2-phenylphenyl) butyl , 5- (3-phenylphenyl) pentyl, 6- (4-phenylphenyl) hexyl, 1, l-dimethyl-2- (2,4-diphenylphenyl) ethyl, 2-methyl-3- (2,4,6-triphenylphenyl) ) propyl, 2- (2-fluorophenyl) ethyl, 1- (3-bromophenyl) ethyl, 3- (4-iodophenyl) propyl, 4- (2-bromophenyl) butyl, 5- (3-chlorophenyl) pentyl, 6- (4-bromoru phenyl) hexyl, 1, l-dimethyl-2- (2,4-dichlorophenyl) ethyl, 2-methyl-3- (2,4,6-trifluorophenyl) propyl, 2- (2-ethylphenyl) ethyl, 1- (3-propylphenyl) ethyl, 3- (4-butylphenyl) propyl, 4- (2-pentylphenyl) butyl, 5- (3-hexylphenyl) pentyl, 6- (4-trifluoromethylphenyl) hexyl, 1, 1-dimethyl -2- (2,4-dimethylphenyl) ethyl, 2-methyl-3- [2,4,6-tri (trifluoromethyl) phenyl] propyl, 2- (2-ethoxyphenyl) ethyl, 1- (3-propoxyphenyl) ethyl , 3- (4-butoxyphenyl) propyl, 4- (2-pentyloxyphenyl) butyl, 5- (3-hexyloxyphenyl) pentyl, 6- (4-trifluoromethoxyphenyl) hexyl, 1, 1-dimethyl-2- (2, 4- d imethoxyphenyl) ethyl, 2-methyl-3- [2,4,6-tri (trifluoromethoxy) phenyl] propyl, 2-methylthiobenzyl, 3-methylthiobenzyl, 4-methylthiobenzyl, 3,4-dirathylthiobenzyl, 2,3-dirathylthiobenzyl, 2 - (2-Ethylthiophenyl) ethyl, 2- (4-methylthiophenyl) ethyl, 1- (3-propylthiophenyl) ethyl, 3- (4-butylthiophenyl) propyl, 4- (2-pentylthiophenyl) butyl, 5- (3-hexylthiophenyl) ) pentyl, 6- (4-methylthiophenyl) hexyl, 1,1-dimethyl-2- (2,4-dimethylthiophenyl) ethyl, 2-ethyl-3- [2, 4, 6 trimethylthiophenyl] propyl, 2-ethyl-4-cyanobenzyl, 3-ethoxy-4-ethoxycarbonylbenzyl, 4-phenyl-3-nitrobenzyl, 3-fluoro-4-methoxybenzyl, 4-trifluoromethyl-3-cyanobenzyl, and 3-trifluoromethoxy-3 -fluorobenzyl. Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have one atom of halogen-corao a substituent include phenyl groups which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a linear or branched alkoxy group having 6 carbon atoms which may have 1 to 3 carbon atoms; halogen as substituents and a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 halogen atoms as substituents such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2- ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2 , 6-dimethylphenyl, 3, 4, 5-trim ethylphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3, -dietoxyphenyl, 2, -dimethoxyphenyl, 2,5- dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-triraethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2- (bromoraethoxy) phenyl, 3- (2-chloroethoxy) phenyl, 4- (2, 3 -dichloropropoxy) phenyl, 4- (4-fluorobutoxy) phenyl, 3- (5-chloropentyloxy) phenyl, 4- (5-bromohexyloxy) phenyl, 4- (5,6-dibromohexyloxy) phenyl, 3,4-di (trifluoromethoxy) ) phenyl, 3, -di (4, 4, -trichlorobutoxy) phenyl, 2,4-di (3-chloro-2-methoxypropyl) phenyl, 2,5-di (3-chloropropoxy) phenyl, 2,6-di (2,2,2-trifluoroethoxy) phenyl, 3,4,5-tri (trifluoromethoxy) phenyl, 4- (2,2,2-trichloroethoxy) phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4- trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2- (bromomethyl) phenyl, 3- (2-chloroethyl) phenyl, 4- (2 , 3-dichloropropyl) phenyl, 4- (4-fluorobutyl) phenyl, 3- (5-chloropentyl) phenyl, 4- (5-bromohexyl) phenyl, 4- (5,6-dibromohexyl) phenyl, 3, 4-di (trifluoromethyl) phenyl, 3,4-di (4, 4, 4-trichlorobutyl) phenyl, 2,4-di (3-chloro-2-methylpropyl) phenyl, 2,5-di (3-) chloropropyl) phenyl, 2,6-di (2,2,2-trifluoroethyl) phenyl, 3,4,5-tri (trifluoromethyl) phenyl, 4- (2,2,2-trichloroethyl) phenyl, 2-methyl-4 -trifluoromethylphenyl, and 3-ethyl-trichloromethylphenyl. Examples of the pyrrolidinyl lower alkyl group which may have, in the pyrrolidine ring, 1 to 3 groups lower alkyl which may have a hydroxyl group as a substituent include pyrrolidinylalkyl groups which may have, in the pyrrolidine ring, 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 groups hydroxyl as substituents and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-) pyrrolidinyl] methyl, 2 - [(1, 2 or 3) pyrrolidinyl] groups ] ethyl, 1 - [(1, 2 or 3) pyrrolidinyl] ethyl, 3 - [(1, 2 or 3) pyrrolidinyl] propyl, 4 - [(1, 2 or 3) pyrrolidinyl] butyl, 5- [(1, 2 or 3) pyrrolidinyl] pentyl, 6 - [(1, 2 or 3) pyrrolidinyl] hexyl, 1, 1-dimethyl-2- [(1, 2 or 3) pyrrolidinyl] ethyl, 2 -methyl-3- [(1, 2 or 3-) pyrrolidinyl] propyl, [1-methyl- (2 or 3) pyrrolidinyl] methyl, 2- [2-ethyl- (1, 3, 4 or 5-) pyrrolidinyl] ethyl, 1- [3-propyl- (1, 2, 4 or 5-) pyrrolidinyl] ethyl, 3- [1-butyl- (2 or 3) pyrrolidinyl] propyl,, 4- [2-pe Nityl- (1, 3, 4 or 5-) pyrrolidinyl] butyl, 5- [3-hexyl- (1, 2, 4 or 5-) pyrrolidinyl] pentyl, 6- [1,2-dimethyl- (3, 4 or 5-) pyrrolidinyl] hexyl, 1, l-dimethyl-2- [1,2,3-triraethyl- (4 or 5-) pyrrolidinyl] ethyl, 2-methyl-3- [l-ethyl-2-methyl- (3, 4 or 5-) pyrrolidinyl] propyl, [1- (2-hydroxyethyl) - (2 or 3) pyrrolidinyl] methyl, [2-hydroxymethyl- (1, 3, 4 or 5) pyrrolidinyl] methyl, 2- [2-hydroxymethyl- (1, 3, 4 or 5-) pyrrolidinyl] ethyl, 1- [3- (3-hydroxypropyl) - (1, 2, 4 or 5- ) pyrrolidinyl] ethyl, 3- [1- (4-hydroxybutyl) - (2 or 3) pyrrolidinyl] propyl, 4- [2- (5-hydroxypentyl) - (1, 3, 4 or 5-) pyrrolidinyl] butyl , 5- [3- (6-hydroxyhexyl) - (1, 2, 4 or 5-) pyrrolidinyl] pentyl, 6- [1,2-dihydroxymethyl- (3, 4 or 5-) pyrrolidinyl] hexyl, 1, -dimethyl-2- [1, 2, 3-trihydroxymethyl- (4 or 5) pyrrolidinyl] ethyl, 2-methyl-3- [2- (1, 2-hydroxyethyl) - (1, 3, 4 or 5- pyrrolidinyl] propyl, and [2- (2, 3, 4-trihydroxybutyl) - (1, 3, 4 or 5) pyrrolidinyl] methyl. Examples of the amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may be having 1 or 2 substituents selected from the group consisting of a phenyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminomethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1, l-dimethyl-2-aminoethyl, N, N-diethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylamidoethyl, (N-ethyl-N-propylamino) methyl, 2- (N-methyl-N-hexylamino) ethyl, phenylaminomethyl, 1-phenylaminoethyl, 2-phenylaminoethyl, 3-phenylaminopropyl, 4-phenylamin obutilo, 5- phenylaminopentyl, 6-phenylarainohexyl, N-methyl-N-phenylaminomethyl, 2- (N-ethyl-N-phenylamino) ethyl, (N-ethyl-N-phenylamino) methyl, and 2- (N-phenyl-N-phenylamino) ethyl. Examples of the tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group include tetrahydrofuryl alkyl groups which may have a hydroxyl group as a substituent in the lower alkyl group and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2 or 3) tetrahydrofuryl] methyl, 2 - [(2 or 3) tetrahydrofuryl] ethyl, 1 - [(2 or 3) tetrahydrofuryl] ethyl, 3- groups [(2 or 3-) tetrahydrofuryl] propyl, 4 - [(2 or 3-) tetrahydrofuryl] butyl, 5- [(2 or 3-) tetrahydrofuryl] pentyl, 6- [(2 or 3) tetrahydrofuryl] hexyl, 1, 1-dimethyl-2- [(2 or 3) -tetrahydrofuryl] ethyl, 2-methyl-3- [(2 or 3) -tetrahydrofuryl] propyl, 1-hydroxy-1 - [(2 or 3) -tetrahydrofuryl] ] methyl, 2-hydroxy-2- [(2 or 3) -tetrahydrofuryl] ethyl, 2-hydroxy-1 - [(2 or 3) -tetrahydrofuryl] ethyl, 3-hydroxy-3- [(2 or 3-) tetrahydrotetrahydrofuryl] propyl, 4-hydroxy-4- [(2 or 3-) tetrah idrofuryl] butyl, 5-hydroxy-5- [(2 or 3-) tetrahydrofuryl] pentyl, 6-hydroxy-6- [(2 or 3-) tetrahydrofuryl] hexyl, 2-hydroxy-1, 1-dimethyl-2- [(2 or 3-) tetrahydrofuryl] ethyl, and 3-hydroxy-2-methyl-3- [(2 or 3- ) tetrahydrofuryl] propyl. Examples of the phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group include, in addition to the phenoxy lower alkyl groups described above, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a nitro group and whose alkyl portion is a linear or branched alkyl group having 1 to 3 carbon atoms; to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3,4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2- (2-ethylphenoxy) ethyl groups, - (3-methylphenoxy) ethyl, 2- (4-methylphenoxy) ethyl, 1- (3-propylphenoxy) ethyl, 3- (4-butylphenoxy) propyl, 4- (2-pentylphenoxy) butyl, - 5- (3- hexylphenoxy) pentyl, 6- (4-methylphenoxy) hexyl, 1,1-dimethyl-2- (2,4-dimethylphenoxy) i) ethyl, 2-methyl-3- (2,4,6-triraethyl phenoxy) propyl, 2- (4-nitro-3-methylphenoxy) ethyl, 4-nitrophenoxymethyl, 3-nitrophenoxymethyl, 2-nitrophenoxymethyl, 2- (2 -nitrophenoxy) ethyl, 2- (4-nitrophenoxy) ethyl, 1- (3-nitrophenoxy) ethyl, 3- (4-nitrophenoxy) propyl, 4- (2-nitrophenoxy) butyl, 5- (3-nitrophenoxy) pentyl, 6- (4-nitrophenoxy) hexyl, 1, l-dimethyl-2- (2,4-dinitrophenoxy) ethyl, and 2-methyl-3- (2,4,6-trinitrofenoxy) propyl. Examples of the lower alkanoyl phenyl group include phenylalkanoyl groups whose alkanoyl portion is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl, 5-phenylpentanoyl, 6-phenylhexanoyl, 2,2-dimethyl-3-phenylpropionyl, and 2-methyl-3-phenylpropionyl. Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group which may have a halogen atom include phenyl groups which may have, in the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms such as phenyl groups, 3, - difluorophenyl, 2-fluorophenyl, 3-bromophenyl, 4-iodophenyl, 4-methylphenyl, 2-methylphenyl, 3-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3, -dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifl / uoromethylphenyl , 4-trifluoromethylphenyl, 2- (bromomethyl) phenyl, 3- (2-chloroethyl) phenyl, 4- (2, 3- dichloropropyl) phenyl, 4- (4-fluorobutyl) phenyl, 3- (5-chloropentyl) phenyl, 4- (5-bromohexyl) phenyl, 4- (5,6-dibromohexyl) phenyl, 3,4-di (trifluoromethyl) phenyl, 3,4-di (4, 4, 4-trichlorobutyl) phenyl, 2,4-di (3-chloro-2-methylpropyl) phenyl, 2,5-di (3-chloropropyl) phenyl, 2,6- di (2,2,2-trifluoroethyl) phenyl, 3,4,5-tri (trifluoromethyl) phenyl, 4- (2,2,2-trichloroethyl) phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4 -trichloromethylphenyl, 2-chloro-4-trifluoromethylphenyl, 3-ethyl-4-fluorophenyl, 3-fluoro-4-trichloromethylphenyl, 2-phenyl-3-trifluoromethyl-4-trifluoromethylphenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl , 4-buraphenyl, 2-iodophenyl, 3-iodophenyl, 2, 3-dibromophenyl, 2,4-diiodophenyl, 2,5-difluorophenyl, 2,6-dichlorophenyl, 2,, 6-trichlorophenyl, 2,4-difluorophenyl, 3, 5-difluorophenyl, 2,6-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6 -dichlorophenyl or, 3, 5-dichlorophenyl, 2,4,6,6-trifluorophenyl, and 2,4-difluorophenyl. Examples of the saturated 5- to 7-membered heterocyclic group formed by mutually linking R20 and R21, R22 and R23, R26 and R27, R29 and R30 or R32 and R33 together with the nitrogen atoms attached thereto, through or not through a Nitrogen atom, an oxygen atom or a sulfur atom, include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups.

Examples of the phenoxy lower alkyl group which may have, on the phenyl ring, a lower alkyl group as a substituent include, in addition to the phenoxy lower alkyl groups described above, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents and whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3-methyl groups; , 4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2- (2-ethylphenoxy) ethyl, 2- (4-methylphenoxy) ethyl, 1- (3-propylphenoxy) ethyl, 3- (4 -butylphenoxy) propyl, 4- (2-pentylphenoxy) butyl, 5- (3-hexylphenoxy) pentyl, 6- (4-methylphenoxy) hexyl, 1, 1-dimethyl-2- (2,4-dimethylphenoxy) ethyl, and 2-methy1-3- (2,4,6-trimethylphenoxy) propyl. More preferred is a compound represented by the general formula (1) or a salt thereof, wherein Xi represents a nitrogen atom or a group -CH =, R1 represents a group -Z-R6, Z represents a group -N ( R8) -B-, a group -BN (R8) -, a group -BO-O- or a group -N (R9a) -CO-N- (R9b) -, R8 represents a hydrogen atom, an alkyl group lower one which may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower group lower alkylsulfonyl or a phenyl lower alkyl group, B represents a group -CO- or a lower alkylene group, Bo represents a lower alkylene group, R9a represents a hydrogen atom or a lower alkyl group, R9b represents a hydrogen atom or a group lower alkyl, R6 represents a group [Formula 43-2] R7 represents a halogen atom or a lower alkyl group which may have a halogen atom as a substituent, m represents an integer of 1 or 2 (when m represents 2, two R7s may be identical or different) and R2 represents an atom of hydrogen, a halogen atom, or a lower alkyl group, Y represents a group -O-, or a group -N (R5) -, R5 represents a hydrogen atom, or a lower alkyl group, A represents a group [Formula 43-3 [ p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, or a lower alkyl group which may have a halogen atom as a substituent, R4 represents a group - (T) XN (R14 ) R15, T represents a group -N (R17) -B3-CO-, a group -B-C0-, or a group -CO-, R17 represents a hydrogen atom, or a lower alkyl group, B3 represents a lower alkylene group, B represents a lower alkenylene group or a lower alkylene group which may have a hydroxyl group as a substituent, 1 represents 0 or 1, R14 represents a hydrogen atom or a group alkyl which may have a hydroxyl group, a substituent, R15 represents (36a) an oxalyl group substituted with piperazinyl which may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (which may have 1 to 3 groups selected from the group consisting of group consisting in a lower alkylenedioxy group and a lower alkoxy group as a substituent (s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent (s) on the piperazine ring, R14 and R15, together with the nitrogen atom at which join, form a heterocyclic group which is a piperidinyl or piperazinyl group, wherein the heterocyclic ring can be substituted by a group selected from the group consisting of (28) a lower alkyl group substituted with phenyl which can be substituted by a group , in the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, an atom of halogen, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a group f enyl lower alkoxy, a hydroxyl group, and a lower alkylenedioxy group (49) a group - (B? 2CO) tN (R20) R21, or (84) a group - (0-? 5) s-CO-N ( R26) R27, B12 represents a lower alkylene group, t represents 0 or 1, R20 and R21, together with the nitrogen atom to which they are attached, form a saturated heterocyclic group which is a group piperidinyl or piperazinyl which, in the heterocyclic ring, may be substituted by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, B15 represents a lower alkylene group, s represents 0 or 1, R26 and R27 they can be identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or a lower alkyl imidazolyl group, and R26 and R27, together with the nitrogen atom to which they are attached, can be attached one to the other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 7 merobes, (wherein the heterocyclic ring can be substituted by 1 to 3 phenyl alkyl groups lower that may have a lower alkylenedioxy group on the phenyl ring). For example, a compound represented by the general formula (1) or a salt thereof is preferred, wherein Xi represents a nitrogen atom, R1 represents a group -Z-R6, Z represents a group -N (R8) -B-, R8 represents a hydrogen atom, or a lower alkyl group which may have a lower alkoxy group as a substituent, B represents a group -CO-, R represents a group [Formula 43-4] R7 represents a halogen atom or a lower alkyl group which may have a halogen atom as a substituent, m represents an integer of 1 or 2 (when m represents 2, two R7s may be identical or different) and R2 represents an atom of hydrogen, Y represents a group -O-, or a group -N (R5) -, R5 represents a hydrogen atom, or a lower alkyl group, A represents a group [Formula 43-5] , p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, or a lower alkyl group which may have a halogen atom as a substituent, R4 represents a group - (T)? -N (R14) R15, T represents a group -N (R17) -B3-CO-, a group -B4-C0-, or a group -CO-, R17 represents an atom of hydrogen, or a lower alkyl group, B3 represents a lower alkylene group, B4 represents a lower alkylene group which may have a hydroxyl group as a substituent, 1 represents 0 or 1, R14 and R15, together with the nitrogen atom to which they bind, form a heterocyclic group which is a piperidinyl or piperazinyl group which, in the heterocyclic ring, can be substituted by (28) a lower alkyl group substituted with phenyl which can be substituted by a lower alkylenedioxy group on the phenyl ring. Another highly preferred example is a compound represented by the general formula (1) or a salt thereof, wherein Xi represents a nitrogen atom, R1 represents a group -Z-R6, Z represents a group -N (R8) -B -, R8 represents a hydrogen atom, or a lower alkyl group which may have a lower alkoxy group as a substituent, B represents a group -CO-, R represents a group [Formula 43-6] R7 represents a halogen atom or a lower alkyl group which may have a halogen atom as a substituent, m represents an integer of 1 or 2 (when m represents 2, two R7s may be identical or different) and R2 represents an atom of hydrogen, Y represents a group -O-, or a group -N (R5) -, R5 represents a hydrogen atom, or a lower alkyl group, A represents a group [Formula 43-7] , p represents 1 or 2, R 3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, or a lower alkyl group which may have a halogen atom as a substituent, R 4 represents a group - (T) XN (R 14 ) R15, R17 represents a hydrogen atom, or a group lower alkyl, B represents a lower alkylene group, B represents a lower alkylene group which may have a hydroxyl group as a substituent, 1 represents 0, R14 and R15, together with the nitrogen atom to which they are attached, form a heterocyclic group which is a piperidinyl or piperazinyl group wherein, in the heterocyclic ring, a substituent selected from the group consisting of (49) a group - (Bi2CO) tN (R20) R21, and (84) a group - ( O-Bis) s-CO-N (R26) R27, B12 represents a lower alkylene group, t represents 0 or 1, R20 and R21, together with the nitrogen atom to which they are attached, form a saturated heterocyclic group which is piperazine or piperidine wherein, in the heterocyclic ring, a substituent which is a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, B 15 represents a lower alkylene group, s represents 0 or 1, R26 and R27, together with the nitrogen atom to which they are bound, bind to each other, directly or through an atom of oxygen or nitrogen atom to form a 6-membered saturated heterocyclic ring, (wherein the heterocyclic ring can be substituted by 1 to 3 phenyl lower alkyl groups which can have a lower alkylenedioxy group as a substituent on the phenyl ring). The methods for producing compounds according to the present invention will be described below. A compound according to the present invention represented by the general formula (1) is produced, in which several groups can be used as Y, for example, according to reaction formulas 1 to 4 below. [Reaction formula 1] [Formula 44] (2) (the) wherein, R1, R2, Xi and A are the same as those described above, Yx represents a group -O-, a group -S- or a group -NH-, and X2 represents a halogen atom. The reaction between the compound (2) and the compound (3) is generally carried out in the presence or absence of a suitable solvent and in the presence or absence of a basic compound. 3. 4 Examples of the inert solvent to be used include aromatic hydrocarbons such as benzene, toluene, and 'xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol , fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethyl sulfoxide, N, N-dimethylformamide, N-methylpyrrolidone, and hexaramethylphosphoric triamide, and a mixture of them. Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide, sodium hydride, hydride of potassium, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, and sodium n-butoxide, and organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo [4.3.0] noneno-5 (DBN), 1,8-diazabicyclo [5.4.0] undecene-7 (DBU), and 1,4- diazabicyclo [2.2.2] octane (DABCO), and a mixture thereof. When the reaction is carried out in the presence of a basic compound, the basic compound is typically used in an equimolar amount to that of the compound (2) and preferably 1 to 10 times that of the compound (2) on a molar basis. The compound (3) is typically used in an amount at least equimolar to that of the compound (2) and preferably 1 to 10 times that of the compound (2) on a molar basis. The reaction is typically carried out at -30 a 200 ° C, and preferably at about -30 to 150 ° C, and is generally completed in about 5 minutes to 80 hours. To this reaction system, an alkali metal halide such as sodium iodide or potassium iodide can be added, and a phase transfer catalyst can be added. Examples of the phase transfer catalyst include quaternary ammonium salts substituted with a group selected from the group consisting of a linear or branched alkyl group having 1 to 18 carbon atoms, an alkyl phenyl group whose alkyl portion is a linear alkyl group or branched having 1 to 6 carbon atoms and a phenyl group, such as tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium fluoride, tetrabutylammonium iodide, tetrabutylammonium hydroxide, tetrabutylammonium hydrogensulfite, tributylmethylammonium chloride, tributylbenzylammonium chloride, tetrapentylammonium chloride, tetrapentylammonium bromide, tetrahexylammonium chloride, benzyldimethyloctylammonium chloride, methyltrihexylammonium chloride, benzyldimethyloctadecanemmonium chloride, methyltridecanilaramonium chloride, benzyltripropylammonium chloride, benzyltriethylammonium chloride, phenyltriethylammonium, tetraethylammonium chloride, tetramethylammonium chloride; phosphonium salts substituted with a linear or branched alkyl group having 1 to 18 carbon atoms such as tetrabutylphosphonium chloride; and pyridinium salts substituted with a linear or branched alkyl group having 1 to 18 carbon atoms such as 1-dodecanylpyridinium chloride. These phase transfer catalysts are used individually or in a combination of two or more types. Typically, the phase transfer catalyst is used in an equimolar amount of 0.1 to 1 times that of compound (2) and preferably 0.1 to 0.5 times that of compound (2) on a molar basis. A compound (Ia) in which Yi represents a group -NH-, can also be produced by reacting a compound (2) with a compound (3) in the presence of an acid instead of a basic compound. Examples of the acid used herein include mineral acids such as acid hydrochloric, sulfuric acid, and hydrobromic acid, and organic acids such as acetic acid, trifluoroacetic acid, and p-toluenesulfonic acid. These acids are used individually or in a mixture of two types or more. A compound (1) wherein Y represents a group -N (R5) -, and R5 represents a group that is not a hydrogen atom, can be produced from a compound (1) wherein Y represents a group -NH- of according to the reaction formula 2. [Reaction formula 2] [Formula 45] (le) (I d) where R1, R2, Xi, A and X2 are the same as those described above, R5a represents a lower alkyl group, phenyl lower alkyl group or cycloalkyl group, R5 represents a hydrogen, lower alkyl group, phenyl group or phenyl lower alkyl group, R5c represents a lower alkanoyl group or benzoyl group, RB represents a hydrogen atom or lower alkyl group, and R5b and RB can be attached to each other together with attached carbon atoms to these groups to form a cycloalkyl ring, provided that the carbon number of the alkyl portion in the group -CHRBR5b of the compound (Id) is 1 to 6. The reaction of the compound (Ib) and the compound (4) is brought to under the same conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The reaction of the compound (Ib) and the compound (5) is carried out, for example, in the presence of a reducing agent and in the presence or absence of a suie solvent. Henceforth, this method is called "method A". Examples of the solvent used herein include water, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, acetonitrile, fatty acids such as formic acid, and acetic acid, ethers such as diethyl ether, tetrahydrofuran , dioxane, monoglyme, and diglyme, aromatic hydrocarbons such as benzene, toluene, and xylene, and halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride and a mixture thereof.

Examples of the reducing agent include fatty acids and alkali metal salts thereof such as formic acid, sodium formate, and sodium acetate, hydride reducing agents such as sodium borohydride, sodium cyanoborohydride, sodium triacetyloxyborohydride, and sodium hydride. lithium aluminum, or a mixture of these hydride reducing agents, and catalytic hydrogen reducing agents such as palladium black, palladium-carbon, platinum oxide, platinum black, and Raney nickel. Using a fatty acid or an alkali metal salt thereof such as formic acid, sodium formate, or sodium acetate as a reducing agent, the suitable reaction temperature is typically from room temperature to about 200 ° C, and preferably about 50 to about 150 ° C. The reaction is completed generally in about 10 minutes to 10 hours. It is preferable to use a fatty acid or an alkali metal salt thereof in a large excess amount with respect to the compound (Ib). Using a hydride reducing agent, the suitable reaction temperature is typically -80 to 100 ° C, and preferably -80 to 70 ° C. The reaction is completed generally in about 30 minutes to 60 hours. The hydride reducing agent is typically used in an equimolar amount 1 to 20 times that of compound (Ib), and preferably 1 to 6 times that of compound (Ib) on a molar basis. Especially using lithium aluminum hydride as a hydride reducing agent, it is preferable to employ an ether such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, or diglyme, or an aromatic hydrocarbon such as benzene, toluene, or xylene, as a solvent. To the reaction system, an amine such as trimethylamine, triethylamine, and N-ethyldiisopropylamine, or molecular sieves such as Molecular Sieve 3A (MS-3A) or Molecular Sieve 4A (MS-4A) can be added. Using a catalytic hydrogen reducing agent, the reaction is preferably carried out in a hydrogen atmosphere typically at a normal pressure at about 20 atm, and preferably at a normal pressure at about 10 atm, or in the presence of a donor. hydrogen such as formic acid, ammonium formate, cyclohexene, or hydrated hydrazine, at a temperature of typically -30 to 100 ° C, and preferably 0 to 60 ° C. The reaction is completed generally in about 1 to 12 hours. The catalytic hydrogen reducing agent is typically used in an amount of from about 0.1% to 40% by weight, and preferably about 1 to 20% by weight based on the compound (Ib). In the reaction of the compound (Ib) and the compound (5), the compound (5) is typically used in at least an amount equimolar to that of the compound (Ib), and preferably in an amount equal to a large excess amount on a molar basis. The reaction is carried out using a compound (5), of which RB and R5b (attached to a carbon atom) are joined together to form a cycloalkyl ring together with the carbon atom in the presence of a hydride reducing agent, as a Starting material. In this case, instead of the compound (5), cycloalkyloxytrialkylsilane such as [(1-ethoxycyclopropyl) oxy] trimethylsilane can be used as the starting material to produce the compound (5) described above in the reaction system. The compound (Id) can also be produced by reacting the compound (Ib) with the compound (5) under the same conditions as in the reaction between the compound (lf) with hydroxylamine of the reaction formula 3 described below, and then reducing the resulting compound represented by the general formula: [Formula 46] (R5b) wherein R1, R2, Xx, RB and R5b are the same as those described above. The same reaction conditions as in method A can be applied to this reduction reaction.

The reaction of the compound (Ib) and the compound (6) is carried out by a method for reacting the compound (Ib) with the carboxylic acid of the compound (6) according to a general reaction to produce an amide bond. This reaction can be carried out by any known reaction to produce an amide bond. Specific examples of the method include: (a) a mixed anhydride acid method, specifically, a method of reacting an alkylhalocarboxylic acid with the carboxylic acid (6) to prepare a mixed acid anhydride, and then reacting the amine (Ib) with the mixed acid anhydride; (b) an active ester method, specifically, a method for preparing, from the carboxylic acid (6), an active ester such as a phenyl ester, p-nitrophenyl ester, N-hydroxysuccinimide ester, or 1-hydroxybenzotriazole ester, or an active amide with benzoxazolin-2-thione, and then reacting the active ester or amide with the amine (Ib); (c) a carbodiimide method, specifically, a method for condensing the carboxylic acid (6) with the amine (Ib) in the presence of an activator such as dicyclohexylcarbodiimide, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (SC), or carbonyldiimidazole; (d) other methods, for example, a method for preparing a carboxylic anhydride from the carboxylic acid (6) by the action of a dehydrator such as acetic anhydride, and then reacting the carboxylic anhydride with the amine (Ib), a method of reacting an ester of the carboxylic acid (6) with a lower alcohol with the amine (Ib) at a high pressure and a high temperature, and a method of reacting an acid halide of the carboxylic acid (6), ie, carboxylic acid halide, with the amine (Ib). The mixed acid anhydride used in the mixed anhydride (a) method described above, which is obtained by a general Schotten-Baumann reaction, is used as such without isolation in the reaction with the amine (2) to produce the compound of the present invention represented by the general formula (le). The Schotten-Baumann reaction described above is carried out in the presence of a basic compound. Examples of the basic compound to be used include compounds commonly used in the Schotten-Baumann reaction, for example, organic bases such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo [ 4.3.0] noneno-5 (DBN), 1,8-diazabicyclo [5.4.0] undecene-7 (DBU), and 1,4-diazabicyclo [2.2.2] octane (DABCO), and inorganic bases including carbonates such such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, metal hydroxides such as sodium hydroxide, hydroxide of potassium, and calcium hydroxide, potassium hydride, sodium hydride, potassium, sodium, sodium amide, and metal alcoholates such as sodium methylate and sodium ethylate. These basic corapuestos are used individually or in a combination of two or more types. The reaction is typically carried out at about -20 to 100 ° C, and preferably at about 0 to 50 ° C. The reaction time is about 5 minutes to 10 hours, and preferably about 5 minutes to 2 hours. The resulting mixed acidic anhydride is reacted with the amine (Ib) typically at about -20 to 150 ° C and preferably at about 10 to 50 ° C. The reaction time is about 5 minutes to 10 hours and preferably about 5 minutes to 5 hours. The mixed acidic acidic acid method is generally carried out in a solvent. Any solvent can be used as long as it is conventionally used in the mixed acidic acidic acid method. Specific examples of the solvent include halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dimethoxyethane, esters such as methyl acetate , ethyl acetate, and isopropyl acetate, and polar aprotic solvents such as N, N-dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric acid triamide, and a mixture thereof. Examples of the alkylhalocarboxylic acid used in the mixed acid anhydride method include methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, and isobutyl chloroformiate. In the mixed acid anhydride method, the carboxylic acid (6), alkylhalocarboxylic acid, and the amine (Ib) may be preferably used in equimolar amounts with each other. However, each of the alkyl halocarboxylic acid and the carboxylic acid (6) can be used 1 to 1.5 times those of the amine (Ib) on a molar basis, respectively. In method (c) for carrying out a condensation reaction in the presence of an activator, the reaction is carried out in a suitable solvent in the presence or absence of a basic compound. Any of the solvents and basic compounds used in the reaction in methods (d) of reacting the amine (Ib) with a carboxylic acid halide described below can be used for this reaction. It is appropriate to use the activator typically in at least an amount equimolar to that of the compound (Ib), and preferably 1 to 5 times that of the compound (Ib) on a molar basis. When WSC is used as an activator, the reaction can be carried out properly if 1- hydroxybenzotriazole and / or an acid such a hydrochloric acid is added to the reaction system. This reaction is typically carried out at about -20 to 180 ° C and preferably at about 0 to 150 ° C, and is typically completed in about 5 minutes to 90 hours. When a method (d) for reacting the amine (Ib) with a carboxylic acid halide is employed, the reaction is carried out in a suitable solvent in the presence of a basic compound. Any basic compound can be used as long as it is widely known in the art. Any basic compound can be used as long as it is used in, for example, the Shotten-Baumann reaction. Examples of the solvent include, in addition to the solvents used in the mixed acid anhydride method, alcohols such as methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, and methyl cellosolve, acetonitrile, pyridine, acetone, and water. The ratio of the amine (Ib) to the carboxylic acid halide is not particularly limited and can be suitably selected from a wide range. Typically, the latter can be used in an amount at least approximately equimolar to that of the former, and preferably approximately 1 to 5 times those of the former on a molar basis. This reaction is typically carried out at about -20 to 180 ° C and preferably at about 0 to 150 ° C, and is typically completed in 5 minutes to 50 hours.

In addition, the reaction to produce an amide bond shown in reaction formula 2 can also be carried out by reacting the carboxylic acid (6) and the amine (Ib) in the presence of a phosphorus compound condensing agent. such as triphenylphosphine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric acid azide, or bis (2-oxo-3-oxazolidinyl) phosphinic chloride. The condensation agent is used individually or in a mixture of two types or more. The reaction is carried out, in the presence of the solvent and the basic compound which are used in the method to react the amine (Ib) with the carboxylic acid halide described above, typically at about -20 to 150 ° C, and preferably at about 0 to 100 ° C, and is typically completed in 5 minutes to about 30 hours. The condensation agent and the carboxylic acid (6) each can be used in at least an amount equimolar to that of the amine (Ib), and preferably about 1 to 2 times that of the amine (Ib) on a base molar. The compound (1), wherein Y represents a group -CH (OH) - or a group -C (= N-0H), is produced from a compound wherein Y represents a group -CO-, according to the formula of reaction 3.

[Reaction formula 3] [Formula 47] (lh) wherein R1, R2, Xi and A are the same as those described above. The compound (lg) is produced by reducing the compound (lf) - In the reduction reaction described above, a reduction method using a hydride reducing agent is favorably used. Examples of the reducing agent that will be used include lithium aluminum hydride, sodium borohydride, borane, diborane, and lithium-trimethoxyborane borohydride. These reducing agents are used individually or in a mixture of two or more types. The reducing agent is typically used in at least an amount equimolar to that of the compound (1f), and preferably 1 to 15 times that of the compound (1f) on a molar basis. This reduction reaction is typically carried out in a suitable solvent, for example, water, a lower alcohol such corao methanol, ethanol, or isopropanol, an ether such as tetrahydrofuran, diethyl ether, diisopropyl ether, or diglyme, or a halogenated hydrocarbon such as dichloromethane, chloroform, or carbon tetrachloride, or a mixture thereof, to about -60 at 150 ° C preferably about -30 to 100 ° C and generally for about 10 minutes to 40 hours. In case lithium aluminum hydride or borane is used as the reducing agentIt is preferable to use an anhydrous solvent such as tetrahydrofuran, diethyl ether, diisopropyl ether, or diglyme. The compound (lh) is produced by reacting the compound (I) and hydroxylamine in a suitable inert solvent in the presence or absence of a basic compound. Examples of the basic compound used herein include inorganic basic compounds such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, and potassium carbonate, alkali metal salts of fatty acids such as sodium acetate, organic bases such such as piperidine, piperidinium acetate, triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo [4.3.0] noneno-5 (DBN), 1,8-diazabicyclo [5.4. 0] undecene-7 (DBU), and 1,4-diazabicyclo [2.2.2] octane (DABCO). These basic compounds can be used individually or in a mixture of two types or more . Any inert solvent can be used as long as it does not adversely affect the reaction. Examples of the inert solvent include water, aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, lower alcohols such such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, dimethyl sulfoxide, N , N-dimethylformamide, and hexamethyl triamide phosphate, and a mixture thereof. The hydroxylamine is typically used in at least an amount equimolar to that of the compound (lf), and preferably 1 to 5 times that of the compound (lf) on a molar basis. The reaction temperature is typically room temperature at 200 ° C and preferably about 50 to 150 ° C. The reaction is completed generally in about 5 minutes to 30 hours. The compound (1), wherein Y represents a group -S (0) n- (n = 1 or 2), is produced from a compound wherein Y represents a group -S-, according to the reaction formula .

[Reaction formula 4 [Formula 48] (lzzzz) (laaaaa) wherein R1, R2, Xx and A are the same as those described above, A? 6 represents a group -A or a group -A10-T2-COOR59a, T2 represents a group -N (R17) -B3-, a group - B19-N (R18) -, a group -B4-, a group -Q-B5-, a group -Be-N- (R19) -B7-, a group -CO-B10-, a group -CH (OH ) -Bu-, a group -B23a-CO-, or a direct link, where R17, B3, B19, R18, B4, B5, B6, R19, B7, B? 0 and Bu are the same as those described above, A10 represents. [Formula 49] group f. - (R3), or group wherein R and p are the same as those described above, provided that a is joined to a group -S or a group -S (0) j, and b is linked to a group -T2, R59a is a hydrogen atom or an alkyl group lower, and j is 1 or 2. The reaction to convert the compound (lzzzz) to the compound (laaaaa) is carried out in a suitable solvent in the presence of an oxidizing agent.

Examples of the solvent include water, fatty acids such as formic acid, acetic acid, and trifluoroacetic acid, alcohols such as methanol and ethanol, and halogenated hydrocarbons such as chloroform and dichloromethane, and a mixture thereof. Examples of the oxidizing agent include percents such as performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloroperbenzoic acid, and o-carboxyperbenzoic acid, hydrogen peroxide, sodium metaperiodate, dicromic acid, dichromates such as sodium dichromate and dichromate. of potassium, permanganic acid, permanganates such as sodium permanganate and potassium permanganate, and polomo salts such as lead tetraacetate. These oxidizing agents are used individually or in a mixture of two or more types. The oxidizing agent is typically suitably used in at least an amount equimolar to that of the compound (lzzzz), and preferably 1 to 2 times that of the compound (lzzzz) on a molar basis. In the oxidation reaction which converts a sulfur atom to a sulfonyl group (j = 2), the oxidizing agent is preferably used in an amount typically at least twice that of the compound (lzzzz) and preferably 2 to 4 times that of the compound (lzzzz) on a molar basis.

The reaction is carried out typically at -10 to 150 ° C, and preferably at about -10 to 100 ° C and is generally completed in about 1 to 100 hours. The compound of the present invention represented by the general formula (1) wherein several groups can be used as A, is produced, for example, according to the following reaction formulas 5 to 36. The compound (1), wherein A represents: [Formula 50] group wherein R represents a lower alkyl imidazolyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring, a 1,2-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl group lower alkyl which may have an oxo group as a substituent on the thiazolidine ring, or a group - (T) ~NR14R15, (T is a lower alkylene group and 1 is 1) is produced by reacting the compound (7); ) with the compound (8) as is shown in reaction formula 5 [Reaction formula 5] [Formula 51] (7) (li) where R1, R2, Yi and Xi are the same as those described above, Al represents [Formula 52] group where R3 and p are the same as those described above, R37a represents a group -B2? -X2, B2? represents a lower alkylene group, and X2 is the same as that described above, and A2 represents [Formula 53] group wherein R3 and p are the same as those described above, R38 represents a group -B2? -R4a, B2? is the same as that described above, R 4a represents an imidazolyl group, a 1,2,4-triazolyl group, a 1,2,3-triazolyl group, a 1,2,5- triazolyl, a pyrazolyl group, a pyrimidinyl group having an oxo group as a substituent on the pyrimidine ring, a 1,2-oxadiazolyl group which may have a lower alkyl group as a substituent on the 1, 2 ring, -oxadiazole, a thiazolidinyl group which may have an oxo group as a substituent on the thiazolidine ring, or a group -NR14R15, and R14 and R15 are the same as those described above. The reaction of the compound (7) with the compound (8) is carried out under the same conditions as in the reaction between the compound (2) and the compound (3) according to the reaction formula 1. The compound (1 ), where A represents [Formula 54] group wherein R 4 is an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, an alkyl pyrazolyl group lower, a lower alkyl pyrimidinyl group having an oxo group as a substituent on the pyrimidine ring, a 1,2-oxadia zol group, or the lower alkyl which may have a lower alkyl group as a substituent on the 1, 2, 4 -oxadia zol ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, or a group - (T)? -NR14R15 (T is a lower alkylene group and 1 is 1) is also produced by reacting the compound (8) with the compound (9) according to the reaction formula 6. [Reaction formula 6] [Formula 55] (9) (lj) wherein R1, R2, Xi and Yi and R4a are the same as those described above, A3 represents [Formula 56] group where R3 and p are the same as those described above, R39 represents a group - (B2?) fC0RA, B2? is the same as that described above, RA represents a hydrogen atom or a lower alkyl group, and f represents 0 or 1, and A4 represents [Formula 57 ^ group or group wherein R3 and p are the same as those described above R 40 represents a group - (B2i) fCHRAR4a, and B21, RA, f and R4a are the same as those described above, provided that the alkyl portion of the group - (B2?) tCHRAR4a does not have more than 6 carbon atoms. The reaction of the compound (9) with the compound (8) is carried out under the same conditions as in the reaction between the compound (Ib) and the compound (5) of the reaction formula 2. The compound (1), where A represents [Formula 58] group wherein R represents a 3,5-dioxoisooxazolidinyl lower alkylidene group which may have an oxo group as a substituent on the 3,5-dioxoisooxazolidine ring, is produced by reacting the compound (11) with the compound (10) of according to the reaction formula 7.

[Reaction formula 7] [Formula 59] (10) (lk) where R1, R2, Xi and Y are equal to those above, and A represents [Formula 60] group wherein R3 and p are the same as those described above, R41 represents a group -B22 (C02R43) (C02R44), B22 represents a lower alkylidene group, and R43 and R44 each represents a lower alkyl group, and A6 represents [Formula 61] group wherein R3 and p are the same as those described above, and R4 is a group represented by [Formula 62 i where B22 is equal to that described above. The reaction of the compound (10) with the compound (11) is carried out under the same condition as in the reaction to convert the compound (lf) to the compound (lh) according to the reaction formula 3. The compound ( 1), where A represents [Formula 63] group where R represents [Formula 64] group is produced from the compound (13), corao is shown in the reaction formula 8.

[Reaction formula 8] [Formula 65] (13) ?? (lm) wherein R1, R2, Xi, Y and R13 are the same as those described above, A7 represents [Formula 66] group wherein R3 and p are the same as those described above, and R 45 represents a halogen atom, A8 represents [Formula 67] group where R3 and p are the same as those described above, and R represents [Formula 68] where R13 is equal to that described above, Ag represents: [Formula 69] group group wherein R3 and p are the same as those described above, and R represents a group [Formula 70] where R, 13 is equal to that described above, and A, 8a represents [Formula 7 1] group wherein R3 and p are the same as those described above, and R 46 ' represents a group [Formula 72] where R, 13 is equal to that described above. The reaction of the compound (13) with the compound (12) is carried out in a suitable inert solvent in the presence of a basic compound. Examples of the basic compound used herein include metallic sodium, metallic potassium, metallic magnesium, sodium hydride, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, and potassium tert-butoxide, and alkyl and aryl lithium. or lithium amides such as methyl lithium, n-butyl lithium, phenyl lithium, and lithium diisopropylamide. These basic compounds are used individually or in a mixture of two types or more. The basic compound is suitably used in a typical manner in at least an amount equimolar to that of the compound (13), and preferably 1 to 5 times that of the compound (13) on a molar basis. Examples of the inert solvent to be used include aromatic hydrocarbons such as benzene, toluene, and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme, aliphatic hydrocarbons such as n-hexane, heptane, and cyclohexane, halogenated hydrocarbons such such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, dimethyl sulfoxide, and N, -dimethylformamide, and a mixture thereof. The reaction is typically carried out at about -90 to 150 ° C and preferably at about -90 to 120 ° C, and is generally completed in about 10 minutes to 10 hours. The compound (12) is suitably used in typical forra at at least an amount equimolar to that of the compound (13) and preferably 1 to 5 times that of the compound (13) on a molar basis. The reaction to convert the compound (11) to the compound (lm) is carried out in a suitable inert solvent and in the presence of an acid. Examples of the acid used herein include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as sulfonic acids including p-toluenesulfonic acid. These acids are used individually or in a mixture of two types or more . The acid is preferably preferably used in at least an amount equimolar to that of the compound (11) and preferably in an amount equal to a large excess amount with respect to the compound (11) on a molar basis. Any solvent can be used in this reaction as long as it is used in the reaction between the compound (13) and the compound (12). This reaction is typically carried out from room temperature to 200 ° C, preferably from room temperature to about 150 ° C, and. It is usually completed in approximately 1 to 20 hours. The reaction to convert the compound (11) to the compound (11 ') is carried out in a suitable solvent and in the presence of an acid and a catalyst. Examples of the solvent used herein include water, lower alcohols such as methanol, ethanol, and isopropanol, ketones such as acetone and methyl ethyl ketone, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran , diisopropyl ether, diglyme, and 1,4-dioxane, aromatic hydrocarbons such as benzene, toluene, and xylene, acetonitrile, dimethyl sulfoxide, N, N-dimethylacetamide, N, N-dimethylformamide, and N-methylpyrrolidone, and a mixture from the same. Examples of the acid used herein include organic in acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, and organic acids such as boron trifluoride diethyl etherate, formic acid, acetic acid, trifluoroacetic acid, and p-toluenesulfonic acid. Examples of the catalyst include alkylsilane compounds such as triethylsilane. The acid and catalyst described above are each typically used in an amount about 0.01 to 5 times that of compound (11), and preferably about 0.01 to 1 times that of compound (11) on a molar basis. The reaction is carried out at about room temperature at 200 ° C, and preferably at about room temperature at 150 ° C, and is generally completed in about 1 to 10 hours. The reaction that converts the compound (11) to the compound (11 ') can be carried out in a suitable solvent and in the presence of a catalytic hydrogen reducing agent. Examples of the solvent to be used include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as n-hexane, alicyclic hydrocarbons such as cyclohexane, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, monoglyme, diglyme, and 1,4-dioxane, esters such as methyl acetate, ethyl acetate, and butyl acetate, and aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, and a mixture thereof. Examples of the catalytic hydrogen reducing agent include palladium, palladium black, palladium-carbon, palladium-carbon hydroxide, rhodium-alumina, platinum, platinum oxide, copper chromite, Raney nickel, and palladium acetate. The catalytic hydrogen reducing agent is typically used in an amount of 0.01 to 1 times that of the compound (11) on a weight basis. The reaction proceeds favorably typically at about -20 to 100 ° C and preferably at about 0 to 80 ° C, and is generally complete in about 0.5 to 20 hours. The hydrogen pressure is typically from 1 to 10 atm. It is preferable to add a mineral acid such as hydrochloric acid to this reaction system. The compound (1), wherein A represents [Formula 73] group where R represents [Formula 74] group wherein R 13 represents a group that is not a hydrogen atom, is produced from a compound wherein R 13 is a hydrogen atom, according to the following reaction formula 9.

[Reaction formula 9] [Formula 75] (lq-2) (lp-2) wherein R1, R2, Xx, Y, Ai0, RA, R13a and X2 are the same as those described above, provided that a and b of A10 are linked to Y and a piperidinyl group, respectively, R13b represents a lower alkyl group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl imidazolyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a piperazylcarbonyl lower alkyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring , or lower alkyl group substituted with morpholinocarbonyl, R13c represents a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a benzoyl group, a lower alkanoyl group substituted with morpholmo, a piperazyl lower alkyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring; or a lower alkanoyl imidazolyl group, and R13d represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a phenyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a rmidazolyl group, a lower alkyl imidazolyl group , a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a piperazylcarbonyl lower alkyl group which may be substituted, on the piperazm ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the ring phenyl, or a lower alkyl group substituted with morpholinocarbonyl, provided that the alkyl portion of the side chain (-CHRAR13d group) of the compound (lq) has no more than 6 carbon atoms. The reaction of the compound (ln-1) with the compound (13 ') is carried out under the same conditions as in the reaction between the compound (Ib) and the compound (4) according to the reaction formula 2. The reaction between the compound (ln-1) and the compound (14) is carried out under the same conditions as in the reaction between the compound (Ib) and the compound (6) according to the reaction formula 2. The reaction between the compound (ln-1) and the compound (15) is carried out under the same conditions as in the reaction between the compound (Ib) and the compound (5) of the reaction formula 2. Also, the reaction between the compound (ln-2) and the compound (13 ') is carried out under the same conditions as in the reaction between the compound (Ib) and the compound (4) according to the reaction formula 2, the reaction between the compound (ln-2) and compound (14) is carried out under the same conditions as in the reaction between compound (Ib) and compound (6) d according to the reaction formula 2, and the reaction between the compound (ln-2) and the compound (15) is carried out under the same conditions as in the reaction between the compound (Ib) and the compound (5) according to the reaction formula 2.

In reaction formula 9, the hydrolysis of the compounds (lo-1) and (lo-2) wherein R 13b represents a lower alkoxycarbonyl lower alkyl group can produce the corresponding compounds (lo-1) and (lo-2) in where R 13b represents a carboxyl lower alkyl group. In reaction formula 9, the hydrolysis of the compounds (lp-1) and (lp-2), wherein R13c represents a lower alkoxycarbonyl group, can produce the corresponding compounds (lp-1) and (lp-2), wherein R13c is a hydrogen atom. The hydrolysis reaction (hereinafter, this hydrolysis reaction will be called "B hydrolysis") can be carried out in the presence or absence of a suitable solvent and in the presence of an acidic or basic compound. Examples of the solvent to be used herein include water, lower alcohols such as methanol, ethanol, isopropanol, and tert-butanol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme, and diglyme, acids fatty acids such as acetic acid and formic acid, esters such as methyl acetate and ethyl acetate, halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride, dimethyl sulfoxide, N, N-dimethylformamide, and hexamethylphosphoric triamide , and a mixture of them. Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid, organic acids such as formic acid, acetic acid, acid trifluoroacetic, sulfonic acids including p-toluenesulfonic acid, and Lewis acids such as boron tribromide and boron trichloride. These acids are used individually or in a mixture of two types or more. Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, and metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and lithium hydroxide. These basic compounds are used individually or in a mixture of two types or more. The hydrolysis reaction favorably proceeds typically at about 0 to about 200 ° C and preferably at about 0 to 150 ° C, and is generally completed in about 10 minutes to 50 hours. The compound (1) wherein A represents [Formula 76] group where R represents [Formula 77] group wherein R, 13 represents a lower alkyl imidazolyl group, is produced as shown in reaction formula 10 below.

[Reaction formula 10] [Formula 78] where R1, R2, Xi, Y, A? 0, R13a, B2? and X2 are the same as those described above, provided that a and b of AlO are linked to Y and a piperidinyl group, respectively. The reaction of the compound (lr-1) and the compound (16) and the reaction of the compound (lr-2) and the compound (16) are carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above.

The compound (1) wherein A represents [Formula 79] group where R represents [Formula 80] group wherein R 13 represents a lower alkanoyl group substituted with morpholino, a piperazinyl lower alkyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a lower alkanoyl imidazolyl group, can be produced from the corresponding compound, wherein R 13 represents a lower alkanoyl group which can have a halogen atom as a substituent, as shown in reaction formula 11 below.

Reaction formula 11] Formula 81] R4 'H (17) R4 'H (17) wherein R1, R2, Xi, Y, R13a, B2i and X2 are the same as those described above, and R47 'is a morpholino group, a piperazinyl group that can be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or an imidazolyl group, provided that a and b of A 0 are attached to Y and a piperidinyl group, respectively. The reaction of the compound (lt-1) and the compound (17) and the reaction of the compound (lt-2) and the compound (17) are carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above . The compound (1) wherein A represents [Formula 82] group where R represents [Formula 83] group wherein R, 1 3 represents a piperazinylcarbonyl lower alkyl group which is substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a lower alkyl group substituted with mor fol inocarboni lo, the corresponding compound is produced wherein R13 is a carboxy group, as shown in reaction formula 12 below.

[Reaction formula 12 '[Formula 84] R4SI1 (18) where R1, R2, Xi, Y, A? 0, R13a and B2? are the same as those described above, R48 is a piperazinyl group which may be substituted, on the piperazine ring, with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, or a morpholino group, provided that a and b of A10 join Y and a piperidinyl group, respectively. The reaction of the compound (lv-1) and the compound (18) and the reaction of the compound (lv-2) and the compound (18) are carried out under the same conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula above. The compound (1) wherein A represents [Formula 85] group wherein R4 represents a group - (T)? -NR14R15, is produced as shown in reaction formulas 13 and 14 below. [Reaction formula 13] [Formula 86] nRl5 wherein R 1, R 2, X 1 R Y, A 0, X 2, 1, R 14 and R 15 are the same as those described above, Ti is a lower alkylene group, a -C0B8- group, a -S02- group or a group - CH (OH) -B9-, and B8 and B9 are the same as those described above, provided that, in compounds (35) and (lpp), a and b of A? 0 join Y and - (T?) ?, respectively. The reaction of the compound (35) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The compound (35) where 1 is 0 can also be producing by reacting the corresponding compound (35) with the compound (36) in a suitable solvent in the presence of a basic compound and a catalyst. Any solvent and basic compound can be used as long as they are used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. Examples of the catalyst include various metal complexes as well as various combinations of a metal complexes with a ligand. Examples of the metal complex include palladium (II) acetate, tetrakis (triphenylphosphine) palladium (0), and tris (dibenzylidene ketone) dipalladium (0). Examples of the ligand include R-2, 2'-bis (diphenylphosphino) -1, 1'-biphenyl (R-BINAP), S-2,2'-bis (diphenylphosphino) -1, l-binaphthyl (S-BINAP) ), RAC-2,2'-bis (diphenylphosphino) -1, l-binaphthyl (RAC-BINAP), t-butylphosphine, and 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene. The catalyst is suitably used in a typical manner in at least an equimolar amount to the compound (35) and preferably 1 to 5 times that of the compound (35) on a molar basis. This reaction is typically carried out at about 0 to 200 ° C and preferably at about 0 to 150 ° C, and is generally completed in about 1 to 60 hours. This reaction will be called "reaction C". [Reaction formula 14] [Formula 87] wherein R2, Xx, Y, Axo, T2, R14 and R15 are the same as those described above, provided that, in compounds (37) and (lqq), a and b of? 0 are bound to Y and T2, respectively, and R95 represents a group R1 or a halogen atom. The R1 used herein is the same as that described above. The reaction of the compound (37) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The compound (1) wherein A represents [Formula 88] group wherein R represents a group? -NR14R15, and 1 represents 0, it may also be produced by the method shown in reaction formula 15. [Reaction formula 15; [Formula 89] (lrr) (lss) where R1, R2, Xi, Y, RA, X2, T, 1 and A? 0 are the same as those described above, R49 is the same group as R15 defined in (15), (22), (23), ( 27) and (36a), R49a is R15 defined in (2) to (5), (7), (8), (10), (11), (13), (14), (16) to (21) ), (24), (25), (26), (26a), (27a), (28a), (29a), (30a), (31a), (32a), (33a), (34a), (35a), or (37a), a phenoxycarbonyl group and a lower alkylsulfonyl group, R, 49b represents a hydrogen atom, a group alkyl which may have a hydroxyl group as a substituent, a phenoxy lower alkyl group, a phenyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom, a group lower alkoxy which may have a halogen atom as a substituent, and a lower alkyl group, a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom, a group lower alkoxy which may have a halogen atom as a substituent, and a lower alkyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a phenyl group which may have a group lower alkylenedioxy on the phenyl ring, a lower alkyl group substituted with lower alkoxycarbonyl, a lower alkyl group substituted with carboxy, a cycloalkyl group at lower alkyl, a cycloalkyl group, a lower alkyl pyridyl group, a pyridyl group, a lower alkyl group substituted with an amino group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group, a group lower alkoxy lower alkyl, an imidazolyl group, a lower alkyl imidazolyl group, a lower alkyl group substituted with 1,2,3,4-tetrahydroisoquinolylcarbonyl, an alkyl carbonyl group lower substituted with a group A, a pyrrolidinyl group, a pyrrolidinyl lower alkyl group, a morpholino group, a lower alkyl morpholino group, an anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a group piperazinyl which may have, in the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an alkyl piperazinyl group lower which may have, in the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an amidino group which may have a lower alkyl group as a substituent, an amidino lower alkyl group which can have a lower alkyl group as a substituent, a lower alkyl carbonyl group substituted with a group B, or a lower alkyl group substituted with cyano, R 1 a represents a hydrogen atom or a lower alkyl group which can have a corao hydroxyl group a substituent, and R34, d, R36, R37 and B2o are equal to those described above, provided that, in the compounds (Irr), (Iss), (lss') and (lss "), a and b of Aio join Y and N, respectively, and, in the compound (lss"), the CHR AnR49b side chain (-Y-A10N (R14a) (CHR, AAnR449ybD) has no more than 6 carbon atoms The reaction of the compound (lrr) and the compound (38a) is carried out under the same conditions as in the reaction of the compound ( Ib) and the compound (4) shown in reaction formula 2 above The reaction of the compound (lrr) with the compound (38) is carried out under the same conditions as in the reaction of the compound (Ib) and the compound (6) shown in reaction formula 2 above The reaction of the compound (lrr) with the compound (38b) is carried out under a condition similar to that of the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above The compound (1) wherein A represents [Formula 90] group wherein R4 represents a group - (T)? -NR14R15, 1 represents 1, and T represents a group -CH (OH) -B9-, can also be produced by the method shown in reaction formula 16 below.

[Reaction formula 16] [Formula 91] (ltt) (luu) where R1, R2, Xi, A? 0, Y, B8, B9, R14 and R15 are the same as those described above, provided that, in the compounds (ltt) and (luu), a_ and b of A? 0 are united a Y already B8 or B9, respectively. The reaction which converts the compound (ltt) to the compound (luu) is carried out under the same condition as in the reaction which converts the compound (lf) to the compound (lg) shown in the reaction formula 3 above. The compound (1) wherein A represents [Formula 92] group wherein R4 represents a group - (T) 1-NR14R15, 1 represents 1, and T represents a group -CH (OH) -Bn-CO-, can also be produced by the method shown in reaction formula 17 below.

[Reaction formula 17] [Formula 93] (lww) wherein R1, R2, Xx, A? 0, Y, Bio, Bu, R14 and R15 are the same as those described above, provided that, in the compounds (lvv) and (lww), a and b of A? 0 are bound to And already a group -COBio or -CH (OH) Bn-, respectively. The reaction which converts the compound (lvv) to the compound (lww) is carried out under the same conditions as in the reaction which converts the compound (lf) to the compound (lg) shown in the reaction formula 3 above. The compound (1) wherein A represents [Formula 94] group wherein R4 is a group - (T)? NR14R15, and R, 14 and R, 15 are joined together to form a 5-10 membered heterocyclic group saturated or unsaturated having several substituents therein, may be produced as shown in the reaction formulas 18 to 20, 22, 24 to 31, and 34 to 36 below. [Reaction formula 18] [Formula 95] (35 ') (l zz) (lbbb) wherein R1, R2, RB, Xi, Y, T, 1, A? 0 and X2 are the same as those described above, provided that a and b of Aio join a group Y and a group (T) I, respectively; R14b and R15a represent the misrao heterocyclic group from 5 to 10 members saturated or unsaturated as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one secondary amine therein; R14c and R15b represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with R50 therein; R14d and R15c represent the same saturated or unsaturated 5- to 10-membered heterocyclic group defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with R51 therein; R14e and R15d represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with a group R52 (RB) CH - in the same; R14f and R15e represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one tertiary amine in it substituted with a group [Formula 96] wherein R50 is the substituent misrao for the heterocyclic ring, which is formed by joining R14 and R15 to each other, which (28), (30), (31), (32), (33), (34), ( 36), (37), (38), (41), (43), (44), (45), (47), (49) (provided that t is 1), (50) (provided that it is 0), (51), (52), (53), (54), (55), (56), (57), (58), (59), (60), (62), (63), (64), (65), (66), (70), (77), (79), (82), (83), (87), (88a), or (90a) described above; R51 is the same substituent for the heterocyclic group, which is formed by joining R14 and R15 to each other, such as (35), (39), (40), (42), (50) (provided that 1 is) , (67), (75), (76), (77), (78), (80), (81) or (84) (provided that s is 0) described above; R52 is a hydrogen atom, a lower alkyl group having 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have an lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, (the lower alkyl group optionally has a pyridyl group in the lower alkyl group), a phenyl group which may have, on the phenyl ring 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group having an alkanoyl group lower as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may having a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxy group, and a lower alkylenedioxy group, a pyridyl lower alkyl group the which may have, in the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyridyl group which may have, on the ring of pyridine, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring, a pyrrolyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring, a benzoxazolyl lower alkyl group, a benzoxazolyl group, a benzothiazolyl group lower alkyl, a benzothiazolyl group, a fuplo lower alkyl group, a furyl group, a lower alkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a halogen atom, a naphthyl lower alkyl group, a group naphthyl, a phenoxy lower alkyl group, a -B? 2CO-NR20R21 group; a -Bi3NR22R23 group, a lower alkyl group substituted with a 1, 2, 3, 4-tetrahdronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1, 2, 3, 4-tetrah? dronaphthalene, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1, 2, 3, 4-tetrahydronaphthalene ring, a quinolyl lower alkyl group, a quinolyl group, a 1,2,3,4-tetrazole or lower alkyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a group 1, 2, 3, 4-tetrazole which may have, in the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring, a thiazolyl group which may have a phenyl group as a substituent on the thiazole ring, a benzoyl lower alkyl group which may have, on the phenyl ring, 1 a 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring, a benzoyl lower alkyl group which may have, in the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl group which may have a lower alkyl group in the piperidine ring, a group 1, 2, 3, 4-tetrahydroquinolyl lower alkyl which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1, 2, 3, 4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, a 1,3,4-diol group oxadiazolyl which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, a cycloalkyl lower alkyl group, a cycloalkyl group, a thienyl lower alkyl group, a thienyl group, a lower alkyl lower alkoxy group, a carboxyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a lower alkyl imidazolyl group, or an imidazolyl group; and RB and R52, together with carbon atoms to which they are attached, can form a cycloalkyl group or a tetrahydro-4H-pyranyl group; provided that the alkyl portion of the group R52 (RB) CH-in the compound (laaa) does not have more than six carbon atoms. The reaction of the compound (35 ') and the compound (39) is carried out under the same conditions as in the reaction of the compound (Ib) with the compound (4) shown in the reaction formula 2 above. The reaction of the compound (35 ') and the compound (40) is carried out under the same conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (35 ') and the compound (41) is carried out under the same conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reaction is carried out using a compound (41), whose RB and R52 (attached to a carbon atom) join together to form a cycloalkyl ring or a tetrahydro-4H-pyran ring together with the carbon atom in the presence of a hydride reducing agent, as a material of departure. In this case, instead of the compound (41), cycloalkyloxytrialkylsilane such a corao [(1-ethoxycyclopropyl) oxy] trimethylsilane can be used as the starting material (to produce the compound (41) described above in the reaction system). The reaction of the compound (35 ') and the compound (42) is carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The compound (35 ') can also be produced from the compound (lyy), (lzz) or (laaa) under the same reaction conditions as in the reaction which converts the compound (liii') to the compound (lhhhJ) shown in the reaction formula 24 below. [Reaction formula 19] [Formula 97] (lccc) (lddd) wherein R1, R2, Xi, Y, T, 1, A? 0 and X2 are the same as those described above, provided that a and b of Aio join Y and a (T) l, respectively; R14g and R15f are the raismo heterocyclic group of 5 to 10 members saturated or unsaturated as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one tertiary amine substituted with a lower alkoxycarbonyl group therein; and R14h and R15g are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one secondary amine therein. The reaction which converts the compound (lccc) into the compound (lddd) can be carried out under the same reaction conditions as in the hydrolysis B as described in reaction formula 9 above. [Reaction formula 20] [Formula 98] (l eee) (lfff) where R1, R2, Xi, Y, T, 1 and A0 are the same as those described above, provided that a and b of A? o join a group Y and a group (T) I, respectively, R74a represents a nitro group or a group -R1, and; R141 and R15h are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the groups heterocyclics has at least one lower alkoxycarbonyl lower alkoxy group, lower alkoxycarbonyl group, lower alkoxycarbonyl lower alkyl group, or a group - (B12CO) tN (R20a) R51 'therein; R1:? and R151 are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one carboxy lower alkoxy group, carboxy group, carboxy lower alkyl group , or a group - (Bi2CO) tN (R20a) R52 'therein; B12 and t are the same as those described above; R20a represents a hydrogen atom, a cycloalkyl group, an amino group which may have a lower alkoxycarbonyl group as a substituent, a benzoyl group which may have 1 to 3 alkoxy groups as substituents on the phenyl ring, a lower alkyl group, a lower alkyl group which may have, on the phenyl ring, substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, and a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group, a phenyl group which may have, on the phenyl ring, 1 to 3 selected substituents of the group that it consists of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a lower alkyl cycloalkyl group, a lower alkyl pyrrolidinyl group which may have, in the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, a lower alkyl group substituted with amino which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group, a lower alkyl group substituted with 1, 2,3,4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring, an alkyl naphthyl group lower, a pyridyl lower alkyl group, a lower alkyl quinolyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, in the ring of t etrazole, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of lower alkyl group and a nitro group, a lower alkanoyl phenyl group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkanoyl imidazolyl group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group, or a group carboxy lower alkyl; R51 'is a lower alkoxycarbonyl group or a lower alkoxycarbonyl lower alkyl group; R52 'is a hydrogen atom or a carboxy lower alkyl group; and R53 is a lower alkyl group. The reaction which converts the compound (leee) into the compound (lfff) can be carried out under the same reaction conditions as those described in hydrolysis B as described in reaction formula 9 above. The reaction of the compound (lfff) and the compound (43) can be carried out under any condition of a typical esterification reaction. For example, the reaction is carried out in the presence of a mineral acid such as hydrochloric acid or sulfuric acid, and a halogenating agent such as thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, or phosphorus trichloride. The compound (43) is used in a large amount excessive to that of compound (lfff). The reaction favorably proceeds typically at about 0 to 150 ° C and preferably at about 50 to 100 ° C, and is completed generally in about 1 to 10 hours. The esterification reaction can be carried out using a condensing agent such as carbodiimide in the presence of a basic compound such as dimethylaminoopyridine. The typical reaction conditions for producing an amide bond can also be used, which are used in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2. The reaction of the compound (lfff) and the compound (43) is carried out in the presence of the same basic compound and solvent as those used in the reaction of compound (2) and compound (3) of reaction formula 1. The reaction is typically carried out at about 0 to 100 ° C and preferably to around 0 to 70 ° C, and is generally completed in about 1 to 30 hours. The compound (leee) can also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the same conditions as in the reaction of the compound (2) and the compound (3) shown in the formula of reaction 1.

[Reaction formula 21] [Formula 99] where R1, R2, Xi, Y, Ai0, R13a, B2? and R53 are the same as those described above, and R54 is a lower alkyl group, provided that a and b of A? 0 are linked to a group Y and a piperidinyl group, respectively. The reaction that converts the compound (lggg-1) into the compound (lv-1) and the reaction that converts the compound (lggg-2) to the compound (lv-2) are carried out under the same reaction conditions as in the hydrolysis B described in the reaction formula 9. The reaction of the compound (lv-1) and the compound (43) and the reaction of the compound (lv-2) and the compound (43) are carried out under the same reaction conditions as in the reaction of the compound (lfff) and the compound (43) shown in the reaction formula above. The compound (lggg-1) can also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the same conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. Similarly, the compound (lggg-2) can also be produced using a halogenated lower alkyl such as methyl iodide in place of the compound (43) under the same conditions as in the reaction of the compound (2) and the co-tax (3) shown in reaction formula 1 above.

[Reaction formula 22] [Formula 100] (lhhh) (liii) where R1, R2, Xi, Y, T, 1 and Ai0 are the same as those described above, provided that a and b of A? 0 join a group Y and a group (T) l, respectively; R14k and R15] are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group -B2? CONHNH2 (wherein B2? is the same as described above) in it; and R141 and R15k are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group [Formula 101] in the same. The reaction that converts the compound (lhhh) into compound (liii) is carried out under the same conditions as in the reaction of the compound (Ib) and the compound (6) shown in reaction formula 2 above, [Reaction formula 23] [Formula 102; (44) (44a) (47) (lrrr) where R1, R2, Xi, Y, A10, B2? and X2 are the same as those described above, provided that a and b of A10 are attached to a group Y and a group (T) I, respectively, R55 is a lower alkanoyl group, and R55a is a lower alkyl group. The reaction of the compound (44) and the compound (45) is carried out under the same conditions as in the reaction which converts the compound (lf) to the compound (lh) shown in the reaction formula 3 above. The reaction of the compound (44a) and the compound (46) it is carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The reaction which converts the compound (47) to the compound (lrrr) is carried out under the same conditions as in the reaction which converts the compound (lf) to the compound (lh) shown in the reaction formula 3 above. [Reaction formula 24] [Formula 103] (lhhh ') (l i i i') wherein R1, R2, Xi, Y, T, 1, A? 0 and X2 are the same as those described above, provided that a and b of A10 join a group Y and a group (T) I, respectively; R14m and R151 are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R above, respectively, except that each of the heterocyclic groups has at least one hydroxyl group or lower alkyl group substituted with one hydroxyl group in the same; R14n and R15m are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 up, respectively, except that each of the heterocyclic groups has at least one -OR56 group therein; R56 represents a phenyl group having, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group the which may have a halogen atom as a substituent, a phenyl lower alkyl group which may have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, a pyridyl lower alkyl group, a lower alkyl group, a lower alkoxy lower alkyl group, a benzoyl group, an alkoxycarbonyl group lower alkyl, a carboxyl lower alkyl group; or a group -B? 5-CO-NR26R27 (wherein B? 5, R26 and R27 are the same as those described above), provided that R56 of the compound (48), which reacts with the heterocyclic group substituted with at least a lower alkyl group substituted with a hydroxy group of the compound (lhhh '), either an unsubstituted phenyl group or a lower alkyl group. The reaction of the compound (lhhh ') and the compound (48) is carried out under the same conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The reaction which converts the compound (liii ') to the compound (lhhh') is carried out under the same conditions as in the hydrolysis B as described in the reaction formula 9 above. The compound (liii ') can be converted to the compound (lhhh') by a reduction reaction. This reduction reaction is, for example, carried out in a suitable solvent in the presence of a catalytic hydrogen reducing agent. Examples of the solvent include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol, aliphatic hydrocarbons such as hexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl ether, monoglyme, and diglyme, esters such as acetate of ethyl and methyl acetate, polar aprotic solvents such as N, N-dimethylformamide, and a mixture thereof. Examples of the catalytic hydrogen reducing agent include palladium, black palladium, palladium-carbon, platinum, platinum oxide, copper chromite, and Raney nickel. These reducing agents can be used individually or as a mixture of two or more types. The catalytic hydrogen reducing agent is preferably used generally in an amount of 0.02 to 1 times that of the compound (liii ') on a weight basis. The reaction temperature is typically set at about -20 to 100 ° C and preferably at about 0 to about 80 ° C. The reaction is preferably carried out at a hydrogen pressure typically of 1-10 atm, and is generally complete in about 0.5 to 20 hours. [Reaction formula 25] [Formula 104] (luuu) (lvvv) (lxxx) where R1, R2, Xi, Y, T, 1, A? 0, RA and X2 are the same as those described above, provided that a. and b of Ai0 join a group Y and a group (T) l, respectively; R140 and R15n are the same heterocyclic group of 5 to 10 saturated or unsaturated members as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one - (B? 2CO) tNHR20a group therein; R14p and R150 are the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one - (B? 2CO) tN (R20a) group R21b therein; and R1 q and R15p are the misrao saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group - (B? 2CO) tN (R20a ) R21c in it; R14r and R15q represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group (B? 2CO) tN (R20a) ( CHRAR21d) in the misrao, where B? 2, t and R20a are equal to those described above; R21b represents a lower alkyl group, a cycloalkyl group, a lower alkyl group which may have 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a lower alkylthio group, a phenyl group which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and an alkyl group lower which may have a halogen atom as a substituent, a lower alkyl cycloalkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, a lower alkyl group substituted with amino which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group , a substituted lower alkyl, 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1, 2, 3, 4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl group lower alkyl, a quinolyl lower alkyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a lower alkyl group; phenyl lower alkyl, a 1,2-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, a lower alkoxycarbonyl group, lower alkyl, a pyridyl group, or a carboxyl lower alkyl group; R21c represents a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a lower alkoxycarbonyl group, a lower alkanoyl phenyl group, a lower alkanoyl group which may have a halogen atom as a substituent or a lower alkanoyl imidazolyl group; and R21d represents a hydrogen atom, a lower alkyl group, a lower alkyl group having 1 or 2 phenyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent and a group lower alkylthio, a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group it consists of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which can be substituted with a halogen atom, a lower alkoxy group which can be substituted with an halogen and a lower alkylthio group, a lower alkyl cycloalkyl group, a cycloalkyl group, a pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, a pyrrolidinyl group which may have, in the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent, a lower alkyl group substituted with amino which may have a group selected from the group consisting of a phenyl group and a lower alkyl group, a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups or as substituents on the 1, 2, 3, 4-tetrahydronaphthalene ring, a 1,2,3,4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3-ring, 4-tetrahydronaphthalene, a naphthyl lower alkyl group, a naphthyl group, a pyridyl lower alkyl group, a pyridyl group, a quinolyl lower alkyl group, a quinolyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, in the tetrazol ring, 1 to 3 3i: substituents selected from the group consisting of a lower alkyl group and a lower alkyl phenyl group, a 1,2,3,4-tetrazolyl group which may have, on the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,4-triazolyl group, a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group, a tetrahydrofuryl group which may have a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a group lower alkyl and a nitro group, a lower alkoxycarbonyl lower alkyl group or a carboxy lower alkyl group; provided that the alkyl portion of CHRAR21d in the side chain (- (B2iCO) tN (R20a) (CHRAR21d)) does not have more than 6 carbon atoms. The reaction of the compound (luuu) with the compound (49) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (luuu) and the compound (51) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reaction of the compound (luuu) and the compound (50) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 26] [Formula 105] (lyyy) (lzzz) wherein R1, R2, Xi, Y, T, 1, and A? 0 are the same as those described above, provided that a and b of A? 0 are joined to Y and a (T) I, respectively; R14s and R15r represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group - (CO) or B? 3X2 therein; R14t and R15s represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group - (CO) or B? 3R84 in the misrao; and R84 is a group -NR22R23 or an imidazolyl group (wherein B13, or, X2, R22 and R23 are the same as those described above). The reaction of the compound (lyyy) and the compound (52) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. [Reaction formula 27] [Formula 106] (laaaa) (lbbbb) wherein R1, R2, Xi, Y, T, 1, and Aio are the same as those described above, provided that a and b of Aio join a group Y and a group (T) I, respectively; R14s 'and R15r' represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -N (R28) -CO- group Bi? X? in the same; and R14u and R15t represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the Heterocyclic groups have at least one group -N (R28) -CO-B? 6NR29R30 therein; (wherein R28, B? 6, X2, R29 and R30 represent the same as those described above). The reaction of the compound (laaaa) and the compound (53) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. [Reaction formula 28] [Formula 107] (lcccc) (ldddd) wherein R74a, R2, Xx, Y, T, 1, and A? 0 are the same as those described above, provided that a and b of A? 0 join a group Y and a group (T) 1, respectively; R14v and R15u represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -B? 2C00H group therein; and R14w and R15v represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -B? 2CONR20R21 group therein; Where B 12 R 20 and R, 21 are the same as those described above). The reaction of the compound (lcccc) and the compound (54) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 29] [Formula 108] (leeee) (lffff) wherein R1, R2, Xi, Y, T, 1, and Aio are the same as those described above, provided that a and b of Ai0 join a group Y and a group (T) I, respectively; R14x and R15w represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -O-B15COOH group; and R14y and R15x represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -0-B? 5CONR26R27 group in the misrao; (where B? 5, R26 and R27 are the same as those described above). The reaction of the compound (leeee) and the compound (55) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 30] [Formula 109] (lgggg) (lhhhh) wherein R1, R2, Xi, Y, T, 1, and A? 0 are the same as those described above, provided that a and b of A? 0 join a group Y and (T) I, respectively; R14z and R15y represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -N (R31) -B? 7- group COOH in it; and i aa and ^ i5z represent the same heterocyclic group from 5 to 10 saturated or unsaturated mierabros as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -N (R31) -B? 7CONR32R33 group therein; (where R31, B? 7, and R32, R33 are the same as those described above). The reaction of the compound (lgggg) and the compound (56) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) of the reaction formula 2 above. [Reaction formula 31] [Formula 110] (liiü) (ljjjj) wherein R1, R2, Xi, Y, T, 1, and A? 0 are the same as those described above, provided that a and b of A? 0 join a group Y and a group (T) I, respectively; R14bb and R15aa represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -COOH group therein; Y R14cc and R15b represent the same saturated or unsaturated 5- to 10-membered heterocyclic group as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one -CONR26R27 group therein; wherein R26 and R27 are the same as those described above. The reaction of the compound (liiii) and the compound (57) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 32] [Formula 111] wherein R1, R2, Xx, Y, T, 1, R14a and Ai0 are the same as those described above, provided that a and b of A? 0 are joined to a group Y and a group (T) I, respectively; h represents 0 or 1; and R 5-7 represents a group lower alkoxycarbonyl. The reaction that converts the compound (Ikkkk) into the compound (11111) can be carried out under the same reaction conditions as in the hydrolysis B described in the reaction formula 9 above. [Reaction formula 33] [Formula 112] (lmmmm) (lnnnn) (loooo) wherein R1, R2, X1 f R3, R4, Y, R11 and R12 are the same as those described above, R58 represents a lower alkyl group, and g represents 0 or 1. The reaction that converts the compound (lmmmm) into the compound ( lnnnn) can be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. The reaction of the compound (lnnnn) with the compound (58) is carried out under the same reaction conditions than in the reaction of the compound (Ib) and the compound shown in the reaction formula 2 above. [Reaction formula 34] [Formula 113] d pppp) (l qqqq) (l ssss) wherein R1, R2, Xi, Y, T, 1, A? 0 and X2 are the same as those described above, provided that a and b of A? 0 are equal to the group Y and a group (T) I, respectively; R14hh and R1599 represent the same saturated or unsaturated heterocyclic groups of 5 to 10 members as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group - (CO) or B? 3NH (R22a) in the same; R1411 and p > 15hh represent the same saturated or unsaturated heterocyclic groups of 5 to 10 members that those defined in R14 and R15 above, except that each of the heterocyclic groups has at least one group - (C0) or -B? 3N (R22a) R23a therein; R1"and R1511 represent the same saturated or unsaturated heterocyclic groups of 5 to 10 members as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group - (CO) 0-B13N ( R22a) R23b therein; R14kk and R15"represent the same saturated or unsaturated heterocyclic groups of 5 to 10 members as defined in R14 and R15 above, respectively, except that each of the heterocyclic rings has at least one group - (CO) oB? 3N (R22a) (CHRAR23c in it, (where RA, B13 and I are the same as those described above) R22a is a hydrogen atom, a lower alkyl group, a benzoyl group that can have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group; R23a represents a lower alkyl group, a group phenoxy lower alkyl which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group; R23b represents a benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring; and R23c represents a hydrogen atom, a lower alkyl group, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group or a phenyl group; provided that the alkyl portion of the group -CHRAR23c in the side chain (- (CO) or -BX3-N (R22a) (CHR? R23c)) of the compound (lssss) has no more than 6 carbon atoms. The reaction of the compound (lpppp) and the compound (59) is carried out under the same reaction conditions as in the reaction of the compound (Ib) y. the compound (4) shown in reaction formula 2 above. The reaction of the compound (lpppp) and the compound (61) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reaction of the compound (lpppp) and the compound (60) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above.

[Fa c e rm a n c e a tio n 3 5] [Formula 114] (l tttt) (luuuu) ^ 27b = 0 (63) (lvvvv) where R1, R2, Xi, Y, T, 1, A? 0 and X2 are equal to those described above, provided that a and b of A? 0 join a group Y and a group (T) l, respectively; R1411 and jp5kk represent the same saturated or unsaturated heterocyclic groups of 5 to 10 members as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group - (0-B? 5) S -CONH (R26a) in it; R14? And R1511 represents the same saturated or unsaturated heterocyclic groups of 5 to 10 members as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one - (O-B15) S group -CON (R26a) (R27a) therein; R n and R represent the same heterocyclic group from 5 to 10 members saturated or unsaturated as defined in R14 and R15 above, respectively, except that each of the heterocyclic rings has at least one group - (O-B15) S-CON (R26a) (CHRAR27b), ( wherein B15, s and RA are the same as those described above 'R2da represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group or a lower alkyl imidazolyl group; R27a represents a lower alkyl group, a phenyl lower alkyl group or an imidazolyl lower alkyl group, and R 27b represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, a phenyl group, an imidazolyl group or a lower alkyl imidazolyl group, provided that the alkyl portion of the -CHRAR27b group in the side chain (- (O-B15) s-CO (R26a) (CHRAR27b)) of the compound (lvvvv) has no more than 6 carbon atoms. The reaction of the compound (ltttt) and the compound (62) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (ltttt) and the compound (63) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 36] [Formula 115] (lcccc ') (lyyyy) (lhhh) where R1, R2, Xx, Y, T, 1, A? 0, R14v, R15u, R14k and R14 are the same as those described above, provided that a and b of Aio join a group Y and a group ( T) l, respectively; R59 represents a lower alkyl group; and R14co and R15nn represent the same saturated or unsaturated heterocyclic groups of 5 to 10 merobes as defined in R14 and R15 above, respectively, except that each of the heterocyclic groups has at least one group -B2? CONHNHCOOR59, (wherein B2? Is the same as described above). The reaction of the compound (lcccc ') and the compound (102) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction that converts the compound (lyyyy) in the compound (lhhh) can be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. The compound of the present invention of the general formula (1) in which several groups are taken as R 1 is produced, for example, as shown by the reaction formulas 37 to 46 below. [Reaction formula 37] [Formula 116] (ly) where R2, Xi, Y, A? 6, R6, R8, B2i, R5, and X2 are the same as those described above, provided that the portion (R6-B2? CHRA-) of the compound (ly) has no more than 6 carbon atoms. The reaction of the compound (19) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and compound (4) shown in reaction formula 2 above. The reaction of the compound (19) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) of the reaction formula 2 above. The reaction of the compound (19) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) of the reaction formula 2 above. [Reaction formula 38] [Formula 117] (Ice) where R2, Xx, Y, A, R6, B, RA and X2 are equal to described above, R8a represents a lower alkyl group which may have a lower alkoxy group as a substituent, a lower alkylsulfonyl group or a lower alkyl phenyl group, R8b represents a hydrogen atom, a phenyl group, a phenyl lower alkyl group or a lower alkyl group which may have a lower alkoxy group as a substituent, and R8c represents a lower alkanoyl group, provided that the alkyl portion of the group -CHRAR8b of the compound (Ice) has not more than 6 carbon atoms. The reaction of the compound (laa) and the compound (23) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (laa) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reaction of the compound (laa) and the compound (25) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above.

[Reaction formula 39 [Paragraph 118] (26) (reads) where R, Xi, Y, A, B2 ?, f, RA and R are the same as those described above, provided that the portion (B2?) fCHRA of the side chain (- (B2?) fCHRANH R6) of the compound ( reads) have no more than 6 carbon atoms. The reaction of the compound (26) and the compound (27) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction Formula 40] [Formula 119] (28) (lff) wherein R represents a group -Y-A or a halogen atom, and R2, Xi, Y, A and R6 are the same as those described above. The reaction of the compound (28) and the compound (27) it is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 41] [Formula 120] (lhh) wherein R2, Xx, Y, A, R6, R8a, R8c, RA and X2 are the same as those described above, provided that the alkyl portion of the group -CHRAR8b of the compound (lhh) does not have more than 6 carbon atoms. The reaction of the compound (lff) and the compound (23) is carried out under the same reaction conditions similar to those of the reaction of the compound (Ib) and the compound (4) shown in reaction formula 2 above. The reaction of the compound (lff) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reaction of the compound (lff) and the compound (25) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 42] [Formula 121] (30) d j j) R6S02X2 (32) (111) (lkk) wherein R2, Xi, Y, A, R6 and X2 are the same as those described above.

The reaction which converts the compound (30) into the compound (ljj) is carried out under the same reaction conditions as in the reaction which converts the compound (lf) to the compound (lh) shown in the reaction formula 3 above. . The reaction that converts the compound (ljj) into the compound (lkk) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reaction of the compound (30) and the compound (32) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. [Reaction formula 43] [Formula 122] (33) (lmm) wherein R2, Xi, Y, A, X2 and R6 are the same as those described above, B3 represents a lower alkylene group or a lower alkenylene group, and the B23-HC = CH- portion in the side chain (R6B23-HC = CH-) of the compound (lmm) has 1 to 3 double bonds and has no more than 6 carbon atoms. The reaction of the compound (33) and the compound (34) it is carried out in a suitable inert solvent and in the presence of a condensing agent. Examples of the inert solvent to be used in the reaction described above include aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride. , lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol, fatty acids such as a-dimethylaminoacetic acid and acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile , l-methyl-2-pyrrolidone, pyridine, dimethyl sulfoxide, dimethylformamide and hexamethylphosphoric acid triamide, and mixtures thereof. Examples of the condensation agent include palladium complexes such as bis (benzonitrile) dichloropalladium (II). The condensing agent is typically favorably used in an amount of 0.01 to 1 times and preferably 0.01 to 0.5 times that of the compound (33) on a molar basis. The reaction described above proceeds favorably typically at 0 to 200 ° C and preferably around the room temperature at about 150 ° C and is generally completed in about 10 minutes to 20 hours. The reaction described above proceeds suitably by adding an alkali metal salt of a fatty acid such as sodium acetate to the reaction system. [Reaction formula 44] [Formula 123] (lnn) (loo) wherein R2, Xi, Y, A and R6 are the same as those described above. The reaction that converts the compound (lnn) to the compound (loo) is carried out under the same reaction conditions as in the reaction that converts the compound (lf) to the compound (lg) shown in the reaction formula 3 above. . [Reaction formula 45] [Formula 124] (64) (lw ww) where Ai7 represents a group [Formula 125] group group wherein R2, R3, p, Xi, Y, A, Bo and R6 are the same as those described above. The reaction of the compound (64) and the compound (65) is carried out in a suitable solvent in the presence of a condensing agent. Any solvent can be used as long as the reaction of a carboxylic acid halide with an amine (Ib) of the reactions between the compound (Ib) and the compound (6) (an amide bond generation reaction) shown is used. in the reaction formula 2. Examples of the condensing agent include a mixture of azocarboxylate (such as diethyl azodicarboxylate) and a phosphorus compound (such as triphenylphosphine). The condensation agent is typically favorably used in an amount at least equimolar to compound (64) and preferably 1 to 2 times that of compound (64) on a molar basis. Compound (65) is typically used in a favorable manner in an amount of at least an equimolar amount to compound (64) and preferably 1 to 2 times that of compound (64) on a molar basis. The reaction described above proceeds favorably in a typical manner at 0 to 200 ° C, preferably at around 0 to 150 ° C and is completed generally in about 1 to 10 hours.

[Reaction formula 46] [Formula 126] (30) (lxxxx) wherein R2, Xi, Y, A and R6 are the same as those described above. The reaction of the compound (30) and the compound (66) is carried out in the presence or absence of a basic compound and preferably in the presence of the basic compound and in the presence or absence of a suitable solvent. Any inert solvent and basic compound can be used as long as they are used in the reaction of a carboxylic acid halide and an amine (Ib) of the reactions between the compound (Ib) and the co-moiety (6) (a link generation reaction) of amide) shown in the reaction formula. The compound (66) can typically be used in an amount of about 1 to 5 times and preferably about 1 to 3 times that of the compound (30) on a molar basis. The reaction described above is typically carried out at 0 to 200 ° C and preferably at about room temperature to 150 ° C and is generally completed in about 5 minutes to 50 hours. A boron compound such as a complex of boron trifluoride-diethyl ether can be added to the reaction system of the reaction described above.

[Reaction formula 47] [Formula 127] (37c) where R2, Xx, Y, T2, A? 0, R14, R15, B2 ?, RA, X2, R6 and R59 are the same as those described above, provided that a and b of Aio join a group Y and a group T2 , respectively. The reaction that converts compound (68) to compound (71) can be carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9 above. The reaction of the compound (71) and the compound (100) is carried out under the reaction conditions as in the reaction of the compound (lfff) and the compound (43) shown in the reaction formula above. Compound (68) can also be produced by using a halogenated lower alkyl group such a corao methyl iodide in place of compound (100) in the same as in the reaction of compound (2) and compound (3) shown in the formula reaction 1 above. The reaction that converts the compound (68) to the compound (69) can be carried out, for example, (1) by reducing the compound (68) with a catalytic hydride reducing agent in a suitable solvent, or (2) by reducing the compound (68) with a reducing agent such a mixture of a metal or a metal salt such as an acid, or a mixture of a metal or a metal salt with an alkali metal hydroxide, a sulfide, an ammonium salt or similar, in a suitable inert solvent.

Examples of the solvent to be used in the method (1) include water, acetic acid, alcohols such as methanol, ethanol and isopropanol, hydrocarbons such as n-hexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl ether and diethylene glycol dimethyl ether, esters such as ethyl acetate and methyl acetate, and polar aprotic solvents such as N, N-dimethylformamide, and a mixture thereof. Examples of the catalytic hydride reducing agent include palladium, palladium black, palladium-carbon, platinum-carbon, platinum, platinum oxide, copper chromite and Raney nickel. These reducing agents can be used individually with a mixture of two types or more. The reducing agent can generally be used in an amount 0.02 to 1 times that of the compound (68) on a weight basis. The reaction temperature is typically set at about -20 to 150 ° C and preferably at about 0 to 100 ° C, and the hydrogen pressure is typically set at 1 to 10 atm. In general, the reaction described above is completed in about 0.5 to 100 hours. An acid such as a hydrochloric acid can be added to the reaction system. The reducing agent for use in the method (2) is a mixture of iron, zinc, tin or stannous chloride with a mineral acid such as hydrochloric acid or sulfuric acid; or a mixture of iron, ferrous sulfate, zinc or tin with an alkali metal hydroxide such as sodium hydroxide, a sulfate such as ammonium sulfate or an ammonium salt such as ammonium hydroxide or ammonium chloride. Examples of the inert solvent include water, acetic acid, alcohols such as methane and ethanol and ethers such as dioxane, and a mixture thereof. The reduction reaction conditions can be suitably selected depending on the reducing agent that will be used. For example, when stannous chloride or hydrochloric acid is used as the reducing agent, the reaction is favorably carried out at about 0 to 150 ° C, for about 0.5 to 10 hours. The reducing agent is used in an amount at least equimolar to compound (68) and typically 1 to 5 times that of compound (68) on a molar basis. The reaction of the compound (69) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (69) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (69) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above.

The reaction that converts the compound (69) into the compound (37a), the reaction that converts the compound (70a) into the compound (37d), the reaction that converts the compound (70b) into the compound (37c) and the reaction which converts compound (70c) to co-tax (37b) is carried out under the same reaction conditions as in hydrolysis B as described in reaction formula 9. The reaction of compound (71) and compound (36) ) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the co-moiety (6) shown in the reaction formula 2. The reaction of the compound (69) and the compound (32) is brought to under the same reaction conditions as in the reaction of the compound (30) and the compound (32) shown in the reaction formula 42 above. [Reaction formula 48] [Formula 128] 4 where R, Xl r Y, A 10, B 3, R 1 R 15 R * R 74a and X are equal to those described above; Rc represents a group -CONR1R15 or a group -COOR59b, R59b represents a lower alkyl group or a phenyl lower alkyl group; R17a represents a lower alkyl group, a cycloalkyl group, a lower alkylsulfonyl group or a lower alkenyl group; R 17b represents a hydrogen atom or a lower alkyl group; and R17c represents a cycloalkylcarbonyl group, a lower alkanoyl group which may have a halogen atom as a substituent or a lower alkanoyl group substituted with amino which may have a lower alkyl group as a substituent (wherein a of A? 0 is attached to a group Y and b binds to a group -NHB3-Rc, a group -N (R17a) B3-Rc, a group -N (CH (RA) (R17b)) B3-Rc or a group -N (R17c) B3-Rc. The reaction of the compound (72a) and the compound (73) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (72a) and the compound (75) is carried out under the same reaction conditions as in the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (72a) and the compound (74) it is carried out under the reaction conditions that in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 49] [Formula 129] wherein R, Xi, Y, Axo, B3, R and R are the same as those described above, R17d represents a lower alkanoyl group having a halogen atom as a substituent, R60 represents an amino group that can be substituted with a group lower alkyl, and R61 represents a lower alkanoyl group substituted with amino that can be substituted with a lower alkyl group, wherein a of Aio joins a group Y and b joins a group -N (R17d) B3-CONR14R15 or a group -NR61B3-CONR14R15. The reaction of the compound (72e) and the compound (76) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above.

[Reaction formula 50] [Formula 130] (78b) where R2, Xi, Y, R6, B2 ?, RA and X2 are the same as those described above, and An represents [Formula 131] wherein R3 and p are the same as those described above, provided that the alkyl portion in the side chain (NHCH group (RA) (B2? R6)) of the compound (78b) has no more than 6 carbon atoms. The reaction that converts the compound (77a) to the compound (77b) is carried out under the same conditions as reaction than the reaction that converts compound (68) to compound (69) shown in reaction formula 47 above. The reaction of the compound (77b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (77b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (77b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the formula 2 above. [Reaction formula 51] [Formula 132] (77c) (37e ') wherein R1, R2, Xx, Y and An are the same as those described above, and i represents an integer from 2 to 4. The reaction of the compound (77c) and the compound (79) it is generally called a Friedel-Crafts reaction and is carried out in a suitable solvent in the presence of a Lewis acid. Any Lewis acid can be used herein as long as it is typically used in the Fr edel-Cra ft reaction. Examples of the Lewis acid include aluminum chloride, zinc chloride, iron chloride, tin chloride, boron tribromide and concentrated sulfuric acid. These Lewis acids are used individually or in a mixture of two types or more. The Lewis acid is typically used in an amount 2 to 6 times that of the compound (77c) on a molar basis. Examples of the solvent to be used herein include aromatics such as carbon disulfide, nitrobenzene and chlorobenzene, halogenated hydrocarbons such as dichloromethane, dichloroethane, carbon tetrachloride and tetrachloroethane, and a mixture thereof. The compound (79) is typically used in at least an equimolar amount in the compound (77c) and preferably 1 to 5 times that of the compound (77c) on a molar basis. The reaction described above proceeds favorably in a typical manner at 0 to 120 ° C and preferably at around 0 to 70 ° C, and is generally completed in about 0.5 to 24 hours.

[Reaction formula 52] [Formula 133] 2 (81b) where R2, Xi, Y, R6, X2, B2? and RA are the same as those described above. Ai2 represents a group [Formula 134] group wherein R3 and p are the same as defined above, and R62 represents a lower alkanoyl group or a lower alkyl group substituted with a hydroxyl group, provided that the alkyl portion in the side chain (-NHCH (RA) group (B2? R6) ) of the compound (81b) does not have more than 6 carbon atoms.

The reaction is converted from the compound (80a) to the compound (80b) is carried out under the same reaction conditions as the reaction that converts the compound (68) into the compound (69) shown in the reaction formula 47 above. . The reaction of the compound (80b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (80b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (80b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 53] [Formula 135] (80b ') (35a) where R1, R2, Xx and Y are the same as above, A? 3 represents a group Fórraula 136] group wherein R and p are the same as those described above, and R63a represents a lower alkanoyl group or a lower alkyl group, and Ai4 represents a group [Formula 137] group wherein R63b represents a lower alkanoyl group which is substituted with a halogen atom in the a position or a lower alkyl group which is substituted with a halogen atom in the 2-position. The reaction which converts the compound (80b ') into the compound (35a) is carried out in the presence of a halogenating agent in a suitable solvent. Examples of the halogenating agent include halogen molecules such as bromine and chlorine, iodine chloride, sulfuryl chloride, copper compounds such as cupric bromide and N-halogenated succinic acid imides such as N-bromosuccinic acid imide and N-acid imide. -chlorosuccí nico.

Examples of the solvent to be used herein include halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, fatty acids such as acetic acid and propionic acid, and carbon disulfide. The halogenating agent is typically favorably used in an amount 1 to 10 times and preferably 1 to 5 times that of the compound (80b ') on a molar basis. The reaction described above is typically carried out at 0 ° C to the boiling point of the solvent and preferably at about 0 to 100 ° C, and is typically completed for about 5 minutes to 30 hours. When an N-halogenated succinic acid imide is used as a halogenating agent, a peroxide such as benzoyl peroxide can be added to the reaction system as a radio initiator.

[Reaction formula 54] [Formula 138] (84d) wherein R2, Xx, Y, Ai0, T2, R59, R8a, R8b, R8c, X2 and RA are the same as those described above and R 64 represents an alkoxycarbonyl phenyl group lower, provided that each of the alkyl portions in the side chain (-N group (CHRAR8b) (R64)) of the compound (84b) and the side chain (-NH (CHRAR8b) group) of the compound (84e) has no more of 6 carbon atoms and a and b_ of Aio are bound to a group Y and a group T2, respectively. The reaction of the compound (83) and the compound (23) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (69) and the compound (82), and the reaction of the compound (83) and the compound (25) are carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in reaction formula 2 above. The reaction of the compound (83) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reactions that convert the compound (84b) into the compound (84d), the compound (84b) into the compound (84e), and the co-phase (84c) into the compound (84f) are carried out under the same reaction conditions that in the reaction in which the compound (liii ') is reduced to convert it to the compound (lhhh') as described in the reaction formula 24 above.

[Reaction Formula 55] [Formula 139] where R2, Xi, Y, A? 0, B2 ?, R74a and X2 are the same as those described above, provided that a and b of Aio join a group Y and a group B2i, respectively. The reaction that converts the compound (85) into the compound (7 ') is carried out by reacting the compound (85) with a halogenating agent in the presence or absence of a suitable solvent. Examples of the halogenating agent include mineral acids such as hydrochloric acid and hydrobromic acid, N, N-diethyl-1,2,2-trichlorovinyl azide, phosphorus pentachloride, phosphorus pentabromide, phosphorus oxychloride, sulfonyl halide compounds such as thionyl chloride, mesyl chloride and tosyl chloride, and a mixture of tetra carbon bromide with triphenylphosphine. The sulfonyl halide compound can be used together with a basic compound. Any basic compound can be used as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. Examples of the solvent to be used include ethers such as dioxane, tetrahydrofuran and diethyl ether, halogenated hydrocarbons such as chloroform, methylene chloride and tetrachloride of carbon and dimethylformamide, and a mixture thereof. When a sulfonyl halide compound serving as a halogenating agent is used as a basic compound, the sulfonyl halide compound is typically favorably used in an amount at least equimolar to that of the compound (85) and preferably 1 to 2 times to that of the compound (85) on a molar basis. The basic compound is typically used in a catalytic amount of the compound (85) and preferably in a catalytic amount to an equimolar amount of the compound (85). When a halogenating agent that is not a sulfonyl halide compound is used, the halogenating agent is used in at least an amount equimolar to that of the compound (85) and is typically used in a large excess amount. The reaction described above proceeds favorably, typically at 200 ° C and preferably at room temperature to 150 ° C, and is generally completed in about 1 to 80 hours. [Reaction formula 56] [Formula 140] where R74a, R2, Xx, Y, A? 0 and B2? they are the same as those described above, and R65 represents a lower trialkylsilyl group, provided that a and b of A10 join a group Y and a group B2 ?, respectively. Examples of the lower trialkylsilyl group to be used herein include trialkylsilyl groups whose alkyl portion is a linear or branched alkyl group having 1 to 6 carbon atoms such as tert-butyldimethylsilyl, trimethylsilyl and diethylmethylsilyl groups. The reaction that converts compound (86) to compound (85) can be carried out under the same reaction conditions as hydrolysis B as described in reaction formula 9 above. [Reaction formula 57] [Formula 141] wherein R a, R, X, Y, A10, B2 ?, R and X2 are the same as those described above, and R66 represents a hydrogen atom, a lower alkyl group or a lower alkoxycarbonyl group, provided that a and b of A? 0 join a group Y and a group B2i, respectively, and each of the alkyl portions on the side chain (-YA? 0-B2? CH2OH) of the compound (85a) and the chain (-Y-A10-B21CH2OR65 ) of the compound (86a) does not have more than 6 carbon atoms. The reaction which converts the compound (69a) into the compound (85a) is carried out under the same reaction conditions as the reaction which converts the compound (lf) into the compound (lg) shown in the reaction formula 3 above.

The reaction of the compound (85a) and the compound (101) is carried out under the same reaction conditions as in the reaction which converts the compound (2) to the compound (3) shown in the reaction formula 1 above. [Reaction formula 58] [Formula 142] (87) (89a) (90b) where R2, Xx, Y, A? 0, B2 ?, R6, RA, f, R43, R44 and X2 are the same as those described above, and B2? < represents an alkylene group lower, provided that a and b of AXo join a group Y and a group B2? -, respectively, and each of the portions (B2? -) f_CH = C in the side chain (-Y-A10- (B2r) f -CH = C (CCOR43) (CCOR44)) of the compound (90c) and the alkyl portion on the side chain (-NHCH (RA) (B2? R6)) of the compound (90b) have no more than 6 carbon atoms, respectively. The reaction of the compound (87) and the compound (88) is carried out under the same reaction conditions as in the reaction of the compound (I) and a hydroxylamine shown in the reaction formula 3 above. The reaction that converts compound (89a) to compound (89b) is carried out under the same reaction conditions as the reaction that converts compound (68) to compound (69) shown in reaction formula 47 above. The reaction of the compound (89b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (89b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (89b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above.

[Reaction formula 59] and formula 143] (91b) where R2, X ?, Y, Ax0, B2, R65, R6, B2i, i and X2 are the same as those defined above, provided that a and b of A? 0 join a group Y and a group B2r, respectively, and the alkyl portion on the side chain (-NHCH (RA) (B2? R6)) of the compound (91b) has no more than 6 carbon atoms. The reaction that converts compound (86a ') to compound (86b) is carried out under the same reaction conditions as in the reaction that converts compound (68) to compound (69) shown in reaction formula 47 above. The reaction of the compound (86b) and the compound (20) it is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (86b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (86b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 60] [Formula 144] (44c) where R2, Xi, Y, Aio, B2 ?, B2? -, R6, RA and X2 are the same as those described above, provided that a and b of A? 0 join a group Y and a group B2i < , respectively, and the alkyl portion on the side chain (-NHCH (RA) (B2iR6)) of the compound (44c) does not have more than 6 carbon atoms. The reaction that converts compound (92a) to compound (92b) is carried out under the same reaction conditions as in the reaction that converts compound (68) to compound (69) shown in reaction formula 47 above. . The reaction of the compound (92b) and the compound (20) is carried out under the reaction conditions as in the reaction of the compound (Ib) and the co-tax (4) shown in the reaction formula 2 above. The reaction of the compound (92b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (92b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above.

[Reaction formula 61] [Formula 145] (94) (95) wherein R2, Xi and X2 are the same as those described above, R67 represents a group -A10B21CN, a group -A? 0-R, a group -A? 0-T2-COOR or a group- TO, R59d represents a lower alkyl group, A? 0, B2 ?, T2 and R59a are the same as those described above, and R68 represents a nitro group or a halogen atom. The reaction of the compound (93) and the compound (94) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. [Reaction formula 62] [Formula 146] (95a) (95b) wherein R2, R67 and Xi are the same as those described above. The reaction of the co-taxa (95a) and the compound (95b) is carried out under the same reaction conditions as in the reaction of the compound (68) and the compound (69) shown in the reaction formula 47 above.

[Reaction formula 63]; Formula 147] (13c) wherein R2, Xi, Y, A7, Rd, B2 ?, RA and X2 are the same as those described above, provided that the alkyl portion in the side chain (-NHCH (RA) (B2? R6)) of the compound (13b) has no more than 6 carbon atoms. The reaction of the compound (96) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (96) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (96) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. Reaction formula 64] [Formula 148] (98b) where R2, Xx, Y, B2 ?, f, i, Rd, B2 ?, A? 0, RA and X2 are equal 4 to those described above, and RA represents a hydrogen atom or a lower alkyl group, provided that the alkyl portion in the side chain (-NHCH (RA) (B2? R6)) in the compound (98b) has not more than 6 carbon atoms, and a_ and b of A? 0 join a group Y and a group (B i) f, respectively. The reaction of the compound (97a) and the compound (97b) is carried out under the same reaction conditions as in the reaction which converts the compound (68) to the compound (69) shown in the reaction formula 47 above. The reaction of the compound (97b) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (97b) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (97b) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in reaction formula 2 above. [Reaction formula 65] [Formula 149] (98d) (9Y where R1, R2, Xi, Y, Aio, B2 ?, f, RA 'and A3 are the same as those described above, provided that a_ and b of Aio join a group Y and a group (B2?) f, respectively . The reaction that converts compound (98d) to compound (9 ') can be carried out under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. [Reaction formula 66] [Formula 150] (B2?) F-CII2NII-T3-C00R59 (9 ') (69b) where R1, R2, Xx, Y, A3, R59, A? 0, B2? and f are the same as those described above, T3 represents a direct link or a group B7, and B7 represents the same as that described above, provided that a and b of A? 0 join a group Y and a group (B2X) f, respectively .

The reaction of the compound (9 ') and the compound (99) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction Formula 67] [Formula 151] (104b) (104c) wherein R2, X1, Y, Ai0, R14a, R49a, R49, R9b, T, 1, RA and X2 are the same as those described above, provided that the CHRA portion in the side chain (-N (R14a) (CHRAR49b) ) of the compound (104c) does not have more than 6, a of Aio joins a group Y and b of Aio joins a group -NR14aH, a group -NR14aR49a, a group -NR14aR49, or a group -NR14a (CHRAR49b) . The reaction of the compound (103) and the compound (38a) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in reaction formula 2 above. The reaction of the compound (103) and the compound (38) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (103) and the compound (38b) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction Formula 68] [Formula 152] (105) (19a) where R, Xi, Y and A are the same as those described above. The reaction which converts compound (105) to compound (19a) is carried out under the same reaction conditions as in the reaction which converts compound (68) to compound (69) shown in reaction formula 47 above. . The compound (19a) can be subjected to the following reaction without isolation.

[Reaction formula 69] [Formula 153] (106a) (106), (19b) where R2, Xi, Y and A0 are the same as those described above, R69a represents a thiazolidinyl group which may have an oxo group as a substituent on the thiazolidine ring, R69 represents a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and R70 represents a thiazolidinyl group lower alkyl which may have an oxo group as a substituent on the thiazolidine ring, provided that from A? 0 it is attached to a group Y and b of A? 0 is attached to a group -R69 or a group -R70. The reaction of the compound (106a) and the compound (160) is carried out under the same reaction conditions as in the reaction of the compound (87) and the compound (88) shown in the reaction formula 58 above. The reaction that converts the compound (106) into the compound (19b) is carried out under the same conditions of reaction than in the reaction that converts compound (68) to compound (69) shown in reaction formula 47 above. [Reaction formula 70] [Formula 154] (109c) (109b) where R2, X1, X2, A, Y1, A10, T2, R59 and R59a are the same as those described above, R71 represents a group -R1 (wherein R1 is the same as that described above), a nitro group or a lower alkoxycarbonyl group, X3 represents a halogen atom and R represents a lower alkyl group which may have a hydroxy group it as a substituent, a nitro group, an amino group which may have an alkanoyl group, a carboxy lower alkyl group, a group - (B2?) f C (= 0) RA (wherein B2?, f and RA are same as those described above), a lower alkanoyl group, a lower alkoxy group or a hydrogen atom; so that from A? 0 you join a group Yi and b from A? 0 join a group -T2 or a group -Fl72. The reaction of the compound (94a) and the compound (107), and the reaction of the compound (94a) and the compound (107a) are each carried out in a suitable solvent and in the presence of a catalyst. Any solvent can be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1. As the catalyst to be used herein, several complexes can be used of metal as well as various combinations of a metal complex and a ligand. Examples of the metal complexes include palladium (II) acetate, tetrakis (triphenylphosphine) palladium (0), and tris (dibenzylidene ketone) dipalladium (0). Examples of the ligand include R-2, 2'-bis (diphenylphosphino) -1, l '-bibinyl (R-BINAP), S-2, 2'-bis (diphenylphosphino) -1, l' -bublthyl (S-BINAP) ), RAC-2, 2'-bis (diphenylphosphino) -1, l'-bilafethyl (RAC-BINAP), t-butylphosphine and 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene. This catalyst is typically favorably used in an amount at least equimolar to the compound (94a) and preferably 1 to 5 times that of the compound (94a) on a base molar. The reaction described above is typically carried out at about 0 to 200 ° C and preferably at about 0 to 150 ° C, and is generally concluded in about 30 minutes to 10 hours. When molecular sieves such as 3A Molecular Sieves (MS3A) or Molecular Sieve 4A (MS4A) or a phosphorus co-phosphate such as triphenylphosphine or tri (2-furyl) phosphine are added to the reaction system, the reaction proceeds suitably. The reaction of the compound (94a) and the compound (108), the compound (3) or the compound (110) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. The compound (109c) in which R71 represents a lower alkoxycarbonyl group can be converted into the corresponding compound (109c) wherein R71 represents a carboxy group, by hydrolyzing it under the same reaction conditions as in the hydrolysis B described in the formula reaction 9 above. [Reaction Formula 71] [Formula 155] (2) (68b) where R1, R2, Xl f X, Yl r Axo and T2 are equal to described above, and R59c represents a hydrogen atom, an alkyl group or a phenyl lower alkyl group, provided that a and b of A? 0 are linked to a group Yi and a group -T2, respectively. The reaction of the compound (2) and the compound (108 ') is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. [Reaction formula 72] [Formula 156] (111) (68c) (Rbb) (RA) C = 0 (5) Rbc0II (6) (68e) (68d) wherein R, Xx, R5a, R, RA, R5c and X2 are the same as those described above, and R73a represents a group -A- or T2-COOR59 (wherein A? 0, T2 and R59 are the same as those described above) or a group -A (where A is equal to that described above), provided that from A? 0 you join a group -NH-, a group -NR5a-, a group - N (CHRAP5b) - or a group -NR5c-, and b of Ai0 binds to a -T2 group, and the alkyl portion on the side chain (-N (R73a) (CHRAR5b)) of the compound (68d) has no more than 6 carbon atoms. The reaction of the compound (111) and the co-tax (4) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (111) and the compound (6) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (111) and the compound (5) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) reacted in the reaction formula 2 above. [Reaction Formula 73] [Formula 157] (112) Ü09d ') wherein R2, X1, Y1, X2, R17, B3, R74a and Rc are the same as those described above, provided that a of A ?0 joins a group -Y and b of Aio joins a group -NHR17 or a group -NR1B3RC. The reaction of the compound (112) and the compound (113) it is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (64) shown in the reaction formula 2 above. [Reaction formula 74] [Formula 158] (114) (I09e) where R2, Xi, Y, A? 0, Ti, 1, R14 and R15 are the same as those described above, provided that a and b of A? 0 join a group -Y and a group - (T?) l, respectively. The reaction of the compound (114) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The compound (109e) in which 1 is 0 can also be produced by reacting the corresponding compound (114) and the compound (36) in a suitable solvent in the presence of a basic compound and a catalyst. The reaction described above is carried out under the same reaction conditions as in reaction C described in reaction formula 13 above.

[Reaction formula 75] [Formula 159] (84j) where R2, Xx, Y, R8, B2X, R6, A? 0, T2, R59, RA and X2 are the same as those described above, provided that the CHRAB2? in the side chain (-N (R8) (CH (RA) B2? R6)) of the compound (84i) does not have more than 6 carbon atoms, and yb of A10 join a group -Y and a group -T2, respectively. The reaction of the compound (84g) and the compound (20) is carried out under the reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (84g) and the co-tax (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in reaction formula 2 above. The reaction of the compound (84g) and the co-tax (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 76] [Formula 160] (1 16c) wherein R2, X1, Y, R8a, R8b, R8c, B, R6, Ai0, T2, R59, RA and X2 are the same as those described above, provided that the CHRA portion in the side chain (-NB (R6) ( CH (RA) R8b)) of the compound (116b) does not have more than 6 carbon atoms, and A and B of Aio are linked to a group -Y and a group -T2, respectively. The reaction of the compound (115) and the compound (23) is carried out under the same reaction conditions as in the reaction of the co-tax (Ib) and the compound (4) shown in reaction formula 2 above. The reaction of the compound (115) and the compound (25) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (15) and the compound (24) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 77] [Formula 161] (117) (118) wherein R2, Xi, Y, A3, R14 and R15 are the same as those described above, and Ai5 represents a group [Formula 162] group wherein R73 represents a group - (B2i) fCH (RA) (NR14R15), and B2i, f and RA are the same as those described above, provided that the portion (B2? fCH (RA) does not have more than 6 carbon atoms. The reaction of the compound (117) and the compound (36) it is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction Formula 78] [Formula 163] (69 ') (1 19) where, R2, X? , Y, Ai0, T2, R6, R9a and R59 are the same as those described above, provided that a and b of Aio join a group -And to a group -T2, respectively. The reaction of the compound (69 ') and the compound (66) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (66) shown in the reaction formula 46 above. [Reaction formula 79] [Formula 164] (120a) (120b) wherein R95, R2, Xi, Y, Ai0, T2 and R59b are the same as those described above, provided that a and b of A? 0 are linked to a -Y group and a -T2 group, respectively.

The reaction that converts compound (120a) to co-tax (120b) can be carried out under the same reaction conditions as in hydrolysis B described for reaction formula 9 above. The reaction of the compound (120b) and the compound (100 ') is carried out under the same reaction conditions as in the reaction of the compound (lfff) and the compound (43) in the reaction formula above. The reaction of the compound (120a) can also produce Lr using a lower alkyl halide such a corao methyl iodide in place of the compound (100 ') under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. [Reaction formula 80] [FórmuLa 165] (120c) (120d) wherein R1, R2, Xi, Y, A? 0, B5, R59a and j are the same as those described above, provided that a. and b from Aio join a group -Y and a group -S, respectively. The reaction that converts the compound (120c) to the compound (120d) is carried out under the same reaction conditions as in the reaction that converts the compound (lzzzz) in the compound (laaaaa) in reaction formula 4 above [Reaction formula 81] [Formula 166] where R2, Xx, Y, Ai0, T, 1, R6, X2, RA, B2? and R14a are the same as those described above, and R49c represents a lower alkoxycarbonyl group, provided that a and b of A? 0 are linked to a -Y group and a - (T) I group, respectively. The reaction of the compound (103) and the compound (38c) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. The reaction that converts compound (104d) into compound (104e) is carried out under the same reaction conditions as in the reaction that converts compound (68) to compound (69) shown in reaction formula 47 above. . The reaction of the compound (104e) and the compound (20) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (104e) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (104e) and the compound (21) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 82] [Formula 167] l where R2, Xi, Y, A3, A? 0, B2? f, RA and i are equal to described above, so that A and B of Aio join a group -Y and a group - (B2?) f, respectively, and the portion (B2?) fC (RA) in the side chain of the compound (123a) does not have more of 6 carbon atoms in total. The reaction of the compound (121) and the compound (122) can be carried out in a suitable solvent in the presence of an acid. Any solvent can be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid and hydrobromic acid, and organic acids such as acetic acid, trifluoroacetic acid and sulfonic acids including p-toluenesulfonic acid. These acids can be used individually or in a mixture of two types or more. The acid is typically favorably used in an amount of at least 0.01 to 5 times and preferably 0.01 to 2 times that of the compound (121) on a molar basis. The compound (122) is suitably suitably used in at least an equimolar amount to the compound (121) and preferably 1 to 10 times that of the compound (121) on a molar basis. The reaction described above is typically carried out at 0 to 200 ° C and preferably at around 0 to 150 ° C and is generally completed in about 30 minutes to 10 hours. [Reaction Formula 83] [Formula 168] (109f) (124) wherein R2, Xx, Y and A? 0 are the same as those described above, and R72a represents a lower alkoxy group, provided that a of A? 0 is attached to a group -Y and b of A? 0 joins a group -R72a or a hydroxyl group. The reaction that converts the compound (109f) to the compound (124) can be carried out in a suitable solvent in the presence of an acid. As the solvent, in addition to aqua, any solvent can be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. Examples of the acid include mineral acids such as hydrobromic acid, hydrochloric acid and concentrated sulfuric acid, fatty acids such as formic acid and acetic acid, organic acids such as p-toluenesulfonic acid, Lewis acids such as aluminum chloride, zinc chloride, iron chloride, tin chloride, boron trifluoride and boron tribromide, iodides such as sodium iodide and potassium iodide, a mixture of a Lewis acid and an iodine as described above. The acid is typically favorably used in an amount of 0.1 to 5 times and preferably 0.5 to 3 times that of the compound (109f) on a molar basis. The reaction described above is typically carried out at 0 to 150 ° C and preferably around 0 to 100 ° C and is generally completed in about 0.5 to 15 hours. [Reaction formula 84] [Formula 169] (124a) (72g) wherein R2, Xx, Y, A0, B5, X2, R14 and R15 are the same as those described above, and Qx represents an oxygen atom or a sulfur atom, provided that a and b of Aio join a -Y group and a group -Qi, respectively. The reaction of the compound (124a) and the compound (125) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above.

[Reaction formula 85] [Formula 170] (109g) (109h) wherein R2, Xi, Y, A10, R14a, R74a, T and 1 are the same as those described above, and R74b represents a lower alkanoyl group or a lower alkoxycarbonyl group, provided that a and b of Ai0 join a -Y group already a group - (T) l, respectively. The reaction which converts the compound (109g) into the compound (109h) can be carried out under the same reaction conditions as in the hydrolysis B described in the reaction formula 9 above. [Reaction formula 86] [Formula 171] where R2, Xx, Y, Ai0, T2, X2, R59a, B23 and R6 are the same as those described above, provided that a and b of A? 0 are linked to the -Y group and to a -T2 group, respectively. The reaction of the compound (126) and the compound (34) it is carried out under the same reaction conditions as in the reaction of the compound (33) and the compound (34) in the reaction formula 43 above. [Reaction formula 87] [Formula 172] (128) (130) (131) wherein R2, Xi, Y, R74a and A? 0 are the same as those described above, R4c represents an amino group or a group -R1 (wherein R1 is the same as described above), R75 represents a lower alkanoyl group, R76 represents a lower alkoxycarbonyl group, R77 and R78 are both lower alkoxy groups and R79 represents a hydrogen atom or a lower alkyl group, provided that a of A? 0 is attached to a -Y group, and b of A? 0 is attached to a group. group -R75, a group -C (R79) = CHR76 or a group -CH (R79) CH2R76, and each of the portions C (R79) = CH and the portion CH (R79) CH2 does not have more than 6 atoms carbon. The reaction of the compound (128) and the compound (129) it is carried out in a suitable solvent in the presence of a basic compound. Any conventional solvent can be used as long as it does not affect the reaction. Examples of this solvent include ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme, aromatic hydrocarbons such as benzene, toluene and xylene, aliphatic hydrocarbons such as n-hexane, heptane and cyclohexane., amines such as pyridine and N, N-dimethylaniline, polar aprotic solvents such as acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide and hexamethylphosphoric acid triamide, and alcohols such as methanol, ethanol and isopropanol and a mixture thereof. Examples of the basic compound include metallic sodium, metallic potassium, sodium hydride, sodium amide, metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, carbonates such as sodium carbonate, potassium carbonate and sodium bicarbonate, metal alcoholates such as sodium methylate, sodium ethylate and potassium tert-butoxide, alkyl and aryl lithium or lithium amides such as lithium raethyld, n-butyryl lithium, phenyl lithium and lithium diisopropylamide, and organic bases such as pyridine, piperidine, quinoline, trimethylamine, diisopropylethylamine and N, N-dimethylaniline. These basic compounds are used individually or in a mixture of two types or more. The basic compound is favorably used in typical form in an amount 0.1 to 10 times and preferably 0.5 to 5 times that of the copolyte (128) on a molar basis.

The compound (129) is typically favorably used at least in an equimolar amount to the compound (128) and preferably one to five times that of the compound (128) on a molar basis. The reaction described above is typically carried out at -80 to 150 ° C and preferably at about -80 to 120 ° C and is generally completed in about 0.5 to 40 hours. When an organic base is used as the basic compound, the reaction suitably proceeds when added to lithium such as lithium chloride to the reaction system. The reaction that converts the co-tax (130) into the compound (131) is carried out under the same reaction conditions as in the reaction which converts the compound (68) to the compound (69) shown in the reaction formula 47 above. [Reaction formula 88] [Formula 173] (28 ') (64a) wherein R2, Xi, Y, R6d and A? 7 are the same as those described above. The reaction which converts the compound (28 ') to the compound (64a) is carried out under the same reaction conditions as in the reaction which converts the compound (lf) to the compound (lg) shown in the reaction formula 3 above.

[Reaction formula 89 ^ [Formula 174] (64b) (26a) wherein R2, Xi, Y and A are the same as those described above. The reaction that converts the compound (64b) to the compound (26a) is carried out in a suitable solvent in the presence of an oxidizing agent. Examples of the solvent include water, fatty acids such as formic acid, acetic acid, trifluoroacetic acid and propionic acid, esters such as ethyl acetate and methyl acetate, alcohols such as methanol, ethanol and isopropanol, ethers such as dioxane, tetrahydrofuran and ether. diethyl ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, chlorobenzene and xylene, and halogenated hydrocarbons such as chloroform and dichloromethane, hexamethylphosphoric acid triamide, N, N-dimethylformamide, dimethyl sulfoxide and pyridine, and a mixture thereof. Examples of the oxidizing agent include percents such as performic acid, peracetic acid, pertrifluoroacetic acid, perbenzoic acid, m-chloroperbenzoic acid and o-carboxyperbenzoic acid, peroxide hydrogen, sodium metaperiodate, dicromic acid, dichromates such as sodium dichromate and potassium dichromate, manganese dioxide, permanganic acid, permanganates such as sodium permanganate and potassium permanganate, lead salts such as lead tetraacetate, silver oxide and a Dess-Martin reagent (Dess-Martin periodinane) These oxidizing agents are used individually or in a mixture of two or more.The oxidizing agent is typically used in at least an equimolar amount to the compound (64b) and preferably 1 to 3 times that of compound (64b) on a molar basis The reaction described above is typically carried out at -10 to 100 ° C and preferably at around 0 to 50 ° C and is completed in about 30 minutes. minutes to 24 hours [Reaction formula 90] [Formula 175] where R2, Xi, Y, A10, B? 9, R18, X2, R14, R74a and R15 are the same as those described above, provided that a and b of A? 0 join a group -Y and a group -B? 9, respectively. The reactions between the compound (133) and the compound (134), and the compound (135) and the compound (36) are each carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. [Reaction formula 91] [Formula 176] lio '-NB, -Rc R17aX2 (73) 17a (108b) (R b) (RA) C = 0 (74) -A10-NH-B3-RC R80-A? 0-N-B3-Rc (108a) CH (RA) (R17b) (108c) R 0H (75 ') Ro? -A10-N-B3-Rc R > 1177 (108d) wherein A? 0, B3, R, 117, aa, R, 117'b ", R", R > 11 ', Yi, Rc and X2 are the same as those described above, and R80 represents the group -YiH or the group -OR81, R81 represents a protecting group of the hydroxyl group, provided that the portion is CHRA in the side chain (-N (B3RC) (CHRRi /)) of the compound (108c) does not have more than 6 atoms of carbon, a of A? 0 joins a group -R80 ', and b joins a group -NHB3RC, a group -N (R17a) B3RC, a group N (CHRAR17b) B3Rc or a group -N ( R? 7) B3Rc. Examples of the protecting group of the hydroxyl group include a phenyl lower alkyl group, a lower alkoxy lower alkyl group, a tetrahydropyranyl group, a trialkylsilyl lower group, a lower alkanoyl group and a lower alkyl group described above. The reaction of the compound (108a) and the compound (73) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (108a) and the compound (75 ') is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (108a) and the compound (74) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. The reaction is carried out using a compound (74), which RA and R17b (attached to a carbon atom) join together to form a cycloalkyl ring together with the carbon atom in the presence of a hydride reducing agent, as a starting material. In this case, instead of the co-pay (74), cycloalkyloxytrialkylsilane starting material such as [(1-ethoxychloropropyl) oxy] trimethylsilane (to produce the compound (74) described above in the reaction system) can be used as the starting material. [Reaction formula 92] [Formula 177] R80 (108g) wherein R80, Ai0, R17, B3, Rc, X2 and R59b are the same as those described above, provided that a of Ai0 joins a group -R80 and b joins a group -NHR17, a group -N (R17) B3RC or a group - N (R17) CH2CH2COOR59. The reaction of the compound (108e) and the compound (113) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (108e) and the compound (137) is carried out low in a suitable solvent in the presence of an acid. Any solvent can be used as long as it is use in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid and hydrobromic acid, organic acids such as acetic acid, trifluoroacetic acid and sulfonic acids including p-toluenesulfonic acid, and Lewis acids such as aluminum chloride, zinc chloride, chloride of iron, tin chloride, boron tribromide and a complex of boron trifluoride / diethyl ether. These acids can be used individually or in a mixture of two types or more. The acid is typically favorably used in an amount at least 0.1 to 5 times and preferably 0.1 to 2 times that of the compound (108e) on a molar basis. The compound (137) is typically favorably used in at least an equimolar amount to the compound (108e) and preferably 1 to 10 times that of the compound (108e) on a molar basis. The reaction described above is typically carried out at 0 to 200 ° C and preferably at around 0 to 150 ° C and is generally completed in about 30 minutes to 80 hours. [Reaction Formula 93] [Formula 178] R81Q _ R73b »». HO- R73b (138) (139) wherein R81 is the same as that described above, R73b represents a group -A- 0 -T2-COR59a or a group -A, and Ai0, T2, R59a and A are equal to those described above, provided that a of AXo joins a group -OR81 or a hydroxyl group, and b of Ai0 joins a group -T2. When R81 of the starting compound (138) represents a phenyl lower alkyl group, the reaction which converts the compound (138) into the compound (139) can be carried out under the same reaction conditions as in the reduction reaction (1 ) (method using a catalytic hydrogen reducing agent), which is one of the reactions that convert compound (68) to compound (69) shown in reaction formula 47 above. The starting compound (138), in which R81 represents a tetrahydropyranyl group or a lower tri-alkylsilyl group is converted to the compound (139), can be carried out under the same reaction conditions as a hydrolysis reaction B described in reaction formula 9 above. In the reaction which converts the compound (138) into the compound (139), the hydrolysis is favorably carried out by the use of an acid. The acid is favorably used in an amount typically 1 to 10 times and preferably 1 to 2 times that of the compound (138) on a molar basis. The compound (138) in which R81 represents a lower tri-alkylsilyl group, can be treated with a fluorine compound such as tetra-n-butylammonium fluoride, hydrogen fluoride or cesium fluoride. The starting compound (138) in which R81 represents a lower alkoxy lower alkyl group or a lower alkyl group, can be treated in a suitable solvent in the presence of an acid. Examples of the solvent include water, lower alcohols such as methanol, ethanol and isopropanol, ethers such as dioxane, tetrahydrofuran and diethyl ether, halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, and polar solvents such as acetonitrile and a mixture thereof. . Examples of the acid include mineral acids such as hydrochloric acid, sulfuric acid and hydrobromic acid, fatty acids such as formic acid and acetic acid, sulfonic acids such as p-toluensulonic acid, Lewis acids such as boron trifluoride, aluminum chloride and boron tribromide, iodides such as sodium iodide and potassium iodide and a mixture of an iodide with a Lewis acid as described above. The reaction described above is typically carried out at 0 to 200 ° C and preferably at about room temperature to 150 ° C and is generally completed in about 0.5 to 25 hours. In addition, hydrolysis can be carried out using a basic compound under the same reaction conditions as in the hydrolysis reaction B described in the reaction formula 9 above. In this case, an amine such as triethylamine may be used other than the basic compounds used in the hydrolysis reaction B, such as the basic compound. The material compound (138), in which R81 represents a lower alkanoyl group, is converted to the compound (139) under the same reaction conditions as in the hydrolysis reaction B described in reaction formula 9 above. The compound (138) in which R73a represents a group [Formula 179] , a dehydration reaction takes place under the above hydrolysis conditions, with the result that the compound (138), in which the corresponding R73a represents a group [Formula 180] , it can be obtained in some cases.

[Reaction formula 94] [Formula 181]) H NH. (36), 14, 15 R -A10-T2-COOH > - Ro? -A? 0-T2-C0N, 15 (140) (108h) wherein R80, A? 0, T2, R14 and R15 are the same as those described above, provided that a and b of Aio are linked to a group -R80 and a group -T2, respectively. The reaction of the compound (140) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 95] [Formula 182] where Yi, A7, R13 and A9 are the same as those described above. The reaction of the compound (141) and the compound (12) is carried out under the same reaction conditions as in the reaction of the compound (13) and the compound (12) shown in the reaction formula 8 above.

[Reaction formula 96] [Formula 183] R8U-A? O- (B2?) RCN R8ü-A? O- (B2?) RCHzNH2 (143) (144) wherein R80, A10, B2i and f are the same as those described above, provided that the alkyl portion in the side chain (- (B2?) f-CH2NH2) of the compound (144) does not have more than 6 carbon atoms. The reaction which converts the compound (143) to the compound (144) is carried out under the same reaction conditions as in the reaction using a hydride reducing agent, which is one of the reactions of the compound (Ib) and the compound (5) shown in reaction formula 2. [Reaction formula 97] [Footnote 184] R80 where R80, Ai0, B19, X2, R18, R14 and R15 are equal to 1 described above, provided that a of A? 0 joins a group -R80 and b joins a group -B19. The reaction of the compound (145) and the compound (134) is carried out under the same reaction conditions as in the reaction of the compound (133)) and the compound (134) shown in the reaction formula 90 above. The reaction of the compound (146) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 98] [Formula 185] wherein Ai0, B19, R14, R15, R80 and X2 are the same as those described above, and R18a represents a lower alkyl group, provided that a and b of Ai0 join a group -R80 and a group -B19, respectively. The reaction of the compound (108j) and the compound (147) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the co-tax (4) shown in the reaction formula 2 above.

[Reaction Formula 99] [Formula 186] (148) (2a) wherein R2, Xi, X2, X3 and R6 are the same as those described above, R82 represents a lower alkyl group and R83 represents a lower alkoxy group. The reaction of the compound (148) and the compound (149) is carried out in a suitable solvent in the presence of a catalyst. Any solvent can be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1. Examples of the catalyst include magnesium. The catalyst is typically favorably used in at least an equimolar amount to compound (148) and preferably 1 to 5 times that of compound (148) on a molar basis. The reaction described above is typically carried out at 0 to 200 ° C and preferably around 0 to 150 ° C and is generally completed in about 30 minutes to 10 hours.

[Reaction Formula 100] [Formula 187] HOOC-Ais X30C-Aif (150) (107 ') wherein Ais represents a group -A or a group -A? 0-T2-COOR, and A, Aio, t2, R59b and 3 are the same as those described above. The reaction which converts the compound (150) into the compound (107 ') is carried out under the same reaction conditions as in the reaction which converts the compound (85) to the compound (7') shown in the reaction formula 55 above. [Reaction formula 101] [Formula 188] (109a ') (151) (152) (153) (154) where R2, Xi, Aio, T2 and R6 are the same as those described above, provided that a of A? 0 is attached to a -CO group, a -CH (OH) group or a -CH2 group, and b of A? 0 join a group -T2. The reaction which converts the compound (109a ') into the compound (151) is carried out under the same reaction conditions as in the reaction using a hydride reducing agent which is one of the reaction between the compound (Ib) and the compound (5) shown in reaction formula 2 above. The reaction that converts compound (151) to compound (152) is carried out under the same reaction conditions as in the reaction that converts compound (68) to compound (69) shown in reaction formula 47 above. . The reaction of the compound (152) and the compound (22) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction which converts the compound (153) into the compound (154) can be carried out under the reaction conditions as in the hydrolysis reaction B described in the reaction formula 9 above.

[Formula for reaction 102] [Formula a 189] (155) (157) wherein R1, R2, Xi, Y, A? 0, B6, B7 or R59 are the same as those described above, and R19a represents a lower alkanoyl group, provided that a and b of A? 0 are attached to a -Y group and a group -B6, respectively. The reaction of the compound (155) and the compound (156) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction formula 103] [Formula 190] wherein R80, A? 0, X2, R14 and R15 are the same as those described above. The reaction of the compound (158) and the compound (36) is carried out under the same reaction conditions as in the reaction of the compound (114) and the ramostrated compound (36) in reaction formula 74 wherein 1 is 0 [Reaction formula 104] [Formula 191] wherein R1, R2, Y, Ai0, R14a, h, T, 1, RB, Xx and X2 are the same as those described above, R85a represents a benzoyl group, R85b represents a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl or furyl lower alkyl group and R85c represents a hydrogen atom, a lower alkyl group, a phenyl group, a phenyl lower alkyl group, a furyl group or a lower alkyl furyl group, provided that the group a -CH (RB) ) R85c of the compound (lbbbbb) no have raas of 6 carbon atoms. The reaction of the compound (lyyy ') and the compound (160') is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (lyyyy ') and the compound (161) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The reaction of the compound (lyyyy ') and the compound (162) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 above. [Reaction formula 105] [Formula 192] (165) (166) 64) (167) (lccccc) where R2, B0, Y, Xi, AX7, R8, X2, X3 and R6 are equal to described above, R86 represents a lower alkylsulfonyl group, and R87 represents an oxygen atom or an -N (R8) - group. The reaction of the compound (165) and the compound (163) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The reaction which converts the compound (165) into the compound (167) is carried out under the reaction conditions as in the reaction which converts the compound (85) to the compound (7 ') of the formula 55 described above. The reaction of the compound (166) or the compound (167) and the compound (164) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above.

[Reaction Formula 106] [Formula 193] 0 = C = N-R15 '(170) R80-A? Or-NH2 * ~ R80-A? Or-NHCONH-R15 (168) (169) wherein R80 and A? 0 are the same as those described above, R15 'represents the same group as that of (5) in R15 described above. The reaction of the compound (168) and the compound (170) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (66) shown in the reaction formula 46 above. [Reaction formula 107] [Formula 194] HNR26R27 (57) R R8? -A, _o- (T), -N R, 880? -A10- (T) N Nnl5aa NR15bb (171) (172) e? "nd Jo, - ,, n., dj, e., DRB0, A? io, rTp, -1i, DR14bb, DR15aa, DR14cc, R D15bb, DR26" and DR27 s _o? n equal to those described above . The reaction of the compound (171) and the compound (57) is carried out under the same reaction conditions as in the reaction of the compound (liiiii) and the compound (57) shown in the reaction formula 31. [Reaction formula 108] [Formula 195] / R bb HNR26R27 (57) sn / 4CC R80-A10- (T)? - N > - R80-A? O- (T)? - NN nldaa nl5bb (171) (172) wherein R1, R2, Xyr Y, A? 0, R15 'and X2 are the same as those described above, and R89 represents a lower alkyl group. The reaction of the compound (173) and the compound (170) is carried out under the same reaction conditions as the reaction of the compound (30) and the compound (66) shown in the reaction formula 46 above. The reaction of the compound (lddddd) and the compound (173) is carried out under the reaction conditions that in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. [Reaction Formula 109] [Formula 196] (174) (lfffff) wherein R 1, R 2, X 1 r Y, X 2, B 3, R 14 and R 15 are the same as those described above, and A 19 represents a group [Formula 197] group A2o represents a group [Formula 198] group where R, p, R, B3, R and R are the same as those described above . The reaction of the compound (174) and the compound (175) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. [Reaction formula 110] [Formula 199] (l ggggg) (lhhhhhh) where R1, R2, Xi and Y are the same as those described above, A2? represents a group [Formula 200] group group and A22 represents a group Formula 201] group group wherein R, p, R1, B3, R and R are the same as those described above. The reaction which converts the compound (lggggg) into the compound (lhhhhh) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) shown in the reaction formula 2 in which a hydride reducing agent is used. [Reaction formula 111] [Formula 202] (lii i i i) (i j j j j j) where R 1, R 2, X i and Y are the same as those described above, A 23 represents a group [Formula 203] group and A24 represents a group Formula 204] group where R and p are the same as those described above. The reaction that converts the compound (liiiii) into the compound (ljjjjj) is carried out under the same reaction conditions as in the reaction that converts the compound (68) to the compound (69) shown in the reaction formula 47. [Reaction formula 112] [Formula 205] (lkkkkk) (l il i l í) where R, Xi and Y are the same as those described above, A25 represents a group [Formula 206] group and A26 represents a group [Formula 207] group wherein B4a represents a lower alkenylene group, 54b represents a lower alkylene group, and R3, p, R14 and R15 are the same as those described above. The reaction which converts the compound (lkkkkk) to the compound (lilily) is carried out in the same manner as the reaction of the method (1) of the reactions which convert the compound (68) to the compound (69) shown in reaction formula 47 above. [Reaction formula 113] [Formula 208] wherein R2, Xi, Y and R59b are the same as those described above, and A28 represents a group [Formula 209] group and A2 represents a group [Formula 210] group wherein R3, p and R59b are the same as those described above. The reaction that converts the compound (lmmmmm) into the compound (Innnnn) is carried out under the same reaction conditions as in the hydrolysis B described in the reaction formula 9 above. The reaction of the compound (Innnnn) and the compound (100 ') is carried out under the same reaction conditions as in the reaction of the compound (lfff) and the compound (43) shown in the reaction formula above. [Reaction formula 114] [Formula 211] (looooo) (lppppp) where R, Xi, X2 and Y are the same as those described above, A29 represent a group [Formula 212] group and A30 represents [Formula 213] group wherein R represents a lower alkyl group which may have a hydroxyl group as a substituent, and R3, p and R 59b are the same as those described above. The reaction of the compound (looooo) and the compound (176) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the formula of reaction 2 above. [Reaction Formula 115] [Formula 214] (lrrrrr) where R, Xi, X2 and Y are the same as those described above, A3? represents a group [Formula 215] group where A32 represents a group [Formula 216] group (Ra9) C00R 59b wherein R3, p, R59b and R89 are the same as those described above. The reaction of the compound (lqqqqq) and the compound (173) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. [Reaction Formula 116] [Formula 217] (lsssss) (lttttt) wherein R1, R2, Xi, Y, A10, T, 1, R90 and X2 are the same as those described above. R15"represents group (2), (3), (4), (5), (6), (7), (8), (10), (11), (12), (13), ( 14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (24), (25), (26) , (27), (26a), (27a), (28a), (29a), (30a), (31a), (32a), (33a), (34a), (35a), (36a) or ( 37a), which is defined in R15 above, the reaction of the compound (lsssss) and the compound (176) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. [Reaction Formula 117] [Formula 218] (luuuuu) (lvvvvv) wherein R1, R2, Xi, Y, A? 0, T and 1 are the same as those described above, R14AA and R15BB each represent the same saturated or unsaturated heterocyclic group of 5 to 10 members as defined in R14 and R15 described above except that the heterocyclic ring has at least one - (B? 2C0) tN (R20 ') -CO-B? 6X2 group therein, R14cc and R15DD each represent the same saturated or unsaturated heterocyclic group of 5 to 10 merobes that the one defined in R14 and R15 described above except that the heterocyclic ring has at least one - (B? 2CO) tN (R20 ') -CO-B? 6R91 -in the same group, wherein B? 2, t, B ? 6 and X2 are the same as those described above. R91 represents an imidazolyl group and R20 'represents a hydrogen atom, a cycloalkyl group, an amino group which can have a group lower alkoxycarbonyl as a substituent, a lower benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring, a lower alkyl group, a lower alkyl group which may have 1 or 2 phenyls which may have, on the phenyl ring , 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a group lower alkoxy which may have a halogen atom as a substituent and a lower alkylthio group which may have a halogen atom as a substituent, or a phenyl group which may be substituted, on the phenyl ring, with 1 to 3 groups selected from the group which consists of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substitute a lower alkoxycarbonyl group, a lower alkyl cycloalkyl group, a lower alkyl pyrrolidinyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl which may have a hydroxyl group as a substituent, a lower alkyl group substituted with amino which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group, a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as substituents on the 1, 2, 3, 4-tetrahydronaphthalene ring, a naphthyl lower alkyl group, a pyridyl lower alkyl group, a lower alkyl quinolyl group, a 1,2,3,4-tetrazolyl lower alkyl group which may have, in the tetrazole ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a tetrahydrofuryl lower alkyl group which may be having a hydroxyl group as a substituent on the lower alkyl group, a phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group, an alkanoyl phenyl group lower, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkanoyl Lmidazolyl group, a lower alkoxycarbonyl lower alkyl group, a pyridyl group or a lower alkyl carboxy group. The reaction of the co-tax (luuuuu) and the compound (177) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above.

[Reaction Formula 118] [Formula 219] (33) (lwwwww) wherein Xi, X2, R2, Y, A and R6 are the same as those described above, and R91 represents a hydrogen atom or a lower alkyl group. The reaction of the compound (33) and the compound (178) is carried out in a suitable solvent in the presence of a basic compound and a catalyst. As the solvent, an inert solvent selected from a wide range can be used. Examples of the inert solvent include water, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, lower alcohols such as methanol, ethanol , isopropanol, butanol, tert-butanol and ethylene glycol, acid grades such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and methyl ethyl ketone, acetonitrile, pyridine, N-methylpyrrolidone, sulfoxide dimethyl, N, N-dimethylformamide and hexamethylphosphoric acid triamide, and a mixture thereof. Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium carbonate and cesium bicarbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, potassium phosphate, phosphate sodium, sodium hydride, potassium hydride, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, n-butoxide, tert-butoxide and tert-butoxide, salts alkylsilylamide alkali metal such as bis (trimethylsilyl) amide, and organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, diraetilaminopiridina, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo [4.3.0] nonen -5- (DBN), 1,8-diazabicyclo [5.4.0] undecen-7 (DBU), and 1,4-diazabicyclo [2.2.2] octane (DABCO) and a mixture thereof. Examples of the catalyst may include palladium compounds such as palladium acetate, bis (tributyltin) / bis (dibenzylideneacetone) palladium, copper iodide / 2, 2 '-bipiridilo, bis (dibenzylideneacetone) palladium, copper iodide / bis ( triphenylphosphine) palladium, tris (dibenzylideneacetone) dipalladium, R- tris (dibenzylideneacetone) -dipalladium, S-tris (dibenzylideneacetone) dialadio, palladium acetate (II), [1, 1 '-bis (diphenylphosphino) ferrocene] dichloropalladium (II), and tetrakis (triphenylphosphine) palladium, compounds such as R -2,2 '-bis (diphenylphosphino) -l, 1'-biphenyl (R-BINAP), S-2, 2'-bis (diphenylphosphino) -1, l-binaphthyl (S-BINAP), RAC-2 , 2'-bis (diphenylphosphino) -1, l'-binaphthyl (RAC-BINAP), and 2,2-bis (difenilimidazolidinilideno), xanthene compounds such as 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene , and borates such as triter-butylphosphine tetrafluoroborate, and a mixture thereof. The basic compound is favorably used in an amount at least 0.5 times and preferably 0.5 to 40 times that of the compound (33) on a molar basis. The catalyst is favorably used in a typical catalyst amount based on the compound (33). The compound (178) is favorably used in an amount at least 0.5 times and preferably 0.5 to 3 times that of the compound (33) on a molar basis. The reaction described above is typically carried out at room temperature at 200 ° C, preferably at room temperature to about 150 ° C and is completed in about 0.5 to 20 hours.

[Reaction Formula 119] [Formula 220] (64) (laaaaaa) wherein B0, Xi, R2, Y, Ai7, R6 and X2 are the same as those described above, R92 represents a group R6-Z4 or a group R6- and Z4 represents a lower alkylene group. The reaction of the compound (64) and the compound (179) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1. [Reaction formula 120] [Formula 221] (30) (lbbbbbb) wherein R2, Xi, Y, A and Rd are the same as those described above. The method for converting the compound (30) to the compound (lbbbbbb) is carried out by subjecting (30) to diazotization to obtain a diazonium salt and reacting the diazonium salt with the compound (180).

The diazotization reaction 1) is carried out in a suitable solvent in the presence of an acid and a diazotization agent. Examples of solvent to be used herein include water and acetonitrile. Examples of the acid include hydrochloric acid, hydrobromic acid, sulfuric acid, tetrafluoroboric acid and hexafluorophosphoric acid. Examples of the diazotizing agent include metal nitrites such as sodium nitrite and potassium nitrite, lower alkyl nitrites such as t-butyl nitrite and isoamyl nitrite. The acid is favorably used in an amount of about 1 to 10 times that of the compound (30) and preferably 1 to 5 times that of the compound (30) on a molar basis. The diazotization agent is typically used in an amount at least approximately equimolar to the compound (30) and preferably 1 to 3 times to that of the compound (30) on a molar basis. The reaction described above is typically carried out at about 0 to 70 ° C and preferably at about 0 ° C at room temperature, and it is completed in approximately a few minutes to 5 hours. The reaction of the diazonium salt obtained in the diazotization reaction and the compound (180) is carried out in the same solvent as in the diazotization reaction of reaction 1) and in the presence of a basic compound.

Any basic compound can be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1. The basic compound is favorably used in at least an equimolar amount to the compound ( 30) and preferably 1 to 5 times that of the compound (30) on a molar basis. The compound (180) is favorably used in at least an equimolar amount to the compound (30) and preferably 1 to 5 times that of the compound (30) on a molar basis. The reaction described above is typically carried out at about 0 to 70 ° C, preferably at about 0 ° C at room temperature, and is completed in about a few minutes to 5 hours. [Reaction Formula 121] [Formula 222] (30a) (lcccccc) where Xi, R8d, Y, A, R2 and R6 are the same as those described above. The reaction of the compound (30a) and the compound (181) can be carried out in a suitable solvent in the presence of a basic compound and a catalyst. Examples of the solvent used herein include water, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme and diglyme, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and tetrachloride of carbon, lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol, fatty acids such as acetic acid, esters such as ethyl acetate and methyl acetate, ketones such as acetone and met i let i lcet ona, acetonitrile, pyridine, dimethyl sulfoxide, N, N-dimethylformamide and hexaramethylphosphoric triamide, and a mixture thereof. Examples of the basic compound include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate and cesium carbonate, metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide, sodium hydride, hydride potassium, potassium, sodium, sodium amide, metal alcoholates such as sodium methylate, sodium ethylate, sodium n-butoxide, sodium tert-butoxide and potassium tert-butoxide, organic bases such as pyridine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1, 5-diazabicyclo [4.3.0] nonen-5 (DBN), 1,8-diazabicyclo [5.4.0] undecen-7 (DBU) and 1,4-diazabicyclo [2.2.2] octane (DABCO) and one mix of them. Examples of the catalyst include palladium compounds such as t e t ra ki s (t r i f en i 1) f ina) pa ladium (0) and dichlorobis (triphenylphosphine) palladium (II), and copper compounds such as copper (II) acetate. The basic compound is favorably used in at least an equimolar amount to the compound (30a) and preferably 1 to 5 times that of the compound (30a) on a molar basis. The catalyst is favorably used in an amount 0.001 to 1 time and preferably 0.01 to 0.5 times to that of the compound (30a) on a molar basis. The compound (181) is favorably used in at least an equimolar amount to the compound (30a) and preferably 1 to 5 times that of the compound (30a) on a molar basis. The reaction described above is typically carried out at -30 to 200 ° C and preferably at 0 to 150 ° C and is generally completed in 0.5 to about 30 hours. A molecular sieve such as 3A molecular sieves (S-3A), 4A molecular sieves (MS-4A) can be added to the reaction.

[Reaction formula 122] [Formula 223] (ldddddd) (1eeeeee; wherein R6, Zi, Xi, R2, Y4 and A are the same as those described above. The reaction that converts the compound (ldddddd) into the compound (leeeeee) is carried out in a suitable solvent in the presence of a catalytic hydrogen reducing agent. Examples of the solvent include water, fatty acids such as acetic acid, alcohols such as methanol, ethanol and isopropanol, aliphatic hydrocarbons such as N-hexane., alicyclic hydrocarbons such as cyclohexane, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, monoglyme, diglyme and 1,4-dioxane, esters such as methyl acetate, ethyl acetate and butyl acetate, and polar aprotic solvents such as N, N-dimethylformamide, N, N-dimethylacetoamide and N-methylpyrrolidone, and mixtures thereof. Examples of the catalytic hydrogen reducing agent include palladium, palladium-black, palladium-carbon, palladium-carbon hydroxide, rhodium-alumina, platinum, platinum oxide, copper chromite, Raney nickel and palladium acetate. The catalytic hydrogen reducing agent described above is typically used in an amount of 0.01 to 1 time to that of the compound (ldddddd) on a molar basis.

The above reaction proceeds favorably typically at about -20 to 150 ° C and preferably at 0 to 100 ° C and is generally complete in 0.5 to 20 hours. The hydrogen pressure can typically be applied at 1 to 10 atm. [Reaction Formula 123] [Formula 224] (lhhhhhh) (lffffff) (l í wherein R1, R2, Xi, Y, A? 0, T and 1 are the same as those described above; R1411 and R15JJ each represent the same saturated or unsaturated heterocyclic group of 5 to 10 members as defined in R14 and R15 above, except that they have at least one phenyl group having a lower alkoxycarbonyl group in the heterocyclic ring; R14EE and R15FF each represent the same saturated or unsaturated heterocyclic group of 5 to 10 members as defined in R14 and R15 above, except that they have at least one phenyl group having a carboxy group in the heterocyclic ring; R14GG and R15HH each represent the same saturated or unsaturated heterocyclic group of 5 to 10 members as defined in R14 and R15 above, except that they have, in the heterocyclic ring, at least one phenyl group which may have a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group; and R93 and R94 each represent a hydrogen atom, a lower alkyl group or a lower alkyl lower alkoxy group. The reaction that converts the compound (lhhhhhh) into the compound (lffffff) can be carried out under the same reaction conditions as in the hydrolysis B described in reaction formula 9 above. The reaction of the compound (lffffff) and the compound (182) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. [Reaction Formula 124] [Formula 225] (ljjjjjj) (lkkkkkk) where Xx, R2, Y, A, X2, k, X3, R6, B2oa and d 'are equal to those described above. The reaction of the compound (30) and the compound (183) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (66) shown in the reaction formula 46 above. The reaction which converts the compound (184) into the compound (Ijjjjjj) is carried out under the reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The reaction of the compound (ljjjjjj) and the compound (185) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. When the compound (185) where d 'represents 0, the reaction which converts the compound (Ijjjjjj) into the compound (Ikkkkkk) can be carried out in a suitable solvent in the presence of a halogenated copper such as copper iodide, an alkyl glycine such as N, N-dimethylglycine, or an alkali metal phosphate such as potassium phosphate. Any solvent can be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. A halogenated copper or an alkyl glycine is used in a typical catalyst amount. The alkali metal phosphate is favorably used in a typical manner in at least one amount equirailar to the compound (ljjjjjj) and preferably 1 to 5 times that of the compound (ljjjjjj) on a molar basis. The compound (185) is used in an amount typically 0.5 to 5 times and preferably 0.5 to 3 times that of the compound (ijjjjjj) on a molar basis. The reaction described above is typically carried out at room temperature at 200 ° C, preferably at about room temperature to 150 ° C and is generally completed in about 1 to 30 hours. [Reaction formula 125] [Formula 226] (33) (í n n i i) wherein X2, R2, Xx, Y, A and R6 are the same as those described above. The reaction of the compound (33) and the compound (186) is carried out under the same reaction conditions as in the reaction of the compound (33) and the compound (178) shown in the reaction formula 118 above.

[Reaction Formula 126] [Formula 227] (33) (lmmmmmm) where Xi, X2, R2, Y, A, B2iar R6 and c are equal to those described above. The reaction of the compound (33) and the compound (187) is carried out under the same reaction conditions as in the reaction of the compound (33) and the compound (178) shown in the reaction formula 118 above. [Reaction Formula 127] [Formula 228] (188) (190) (lnnnnnn) wherein R9a, R2, R6, Xi, Y, Ai6, X2 and R9b are the same as those described above. The reaction of the compound (188) and the compound (189) is carried out under the same reaction conditions as in the reaction in which an amine is reacted with a carboxylic acid halide between the methods (d) in which the compound (Ib) is reacted with the compound (6) shown in the reaction formula 2. The reaction of the compound (190) and the compound (191) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in reaction formula 1 above. [Reaction Formula 128] [Formula 229] (loooooo) (lpppppp) wherein R1, R2, Xx, Y and Ai6 are the same as those described above. Xa represents a halogen atom. The reaction that converts to the compound (loooooo) in the compound (lpppppp) is carried out in a suitable solvent in the presence of a catalytic hydrogen reducing agent and a hydrogen donor such as formic acid, ammonium formate, cyclohexene or hydrated hydrazine. Any solvent and catalytic hydrogen reducing agent can be used as long as it is used in the reaction that converts the compound (ldddddd) to the compound (leeeeee) shown in reaction formula 22 above. The catalytic hydrogen reducing agent is typically used in an amount of 0.01 to 40% by weight and preferably 0.01 to 20% by weight of the compound (looocoo). The hydrogen donor is typically used in at least one-equimolar amount to the compound (loooooo) and preferably 1 to 10 times that of the compound (loooooo) on a molar basis. The reaction described above is carried out under a hydrogen atmosphere typically at around normal pressure at 20 atm and preferably at normal pressure at 10 atm, and at a temperature of about -30 to 150 ° C and preferably around from 0 to 100 ° C. The reaction is completed generally in about 1 to 12 hours. [Reaction formula 129] [Formula 230] Ra? -A 1 Q-1NH2 R8U-A? 0 -NHC0NH (CH2) kX2 X2- (CH2) k -N = C = 0 (192) (183) (193) wherein A? 0, X2,, X3, R80 and RB are the same as those described above; R94a represents a group defined as a substituent present in a heterocyclic group formed by linking R14 and R15 to each other, and include a substituent represented by (35), (40), (42), (67), (75), (76 ), (78), (80) u (81) in which o is 1, u (84) in which s is 0. R9 b represents a group defined as a substituent present in a heterocyclic ring formed by joining R14 and R15 to each other, and include a substituent represented by (28), (30) to (34), (36) to (39), (41), (43) a (45), (47), (52) to (60), (62) to (66), (70), (77), (79), (82), (83), (87), (88a) ) or (90a), a substituent represented by (49) in which t is 1, or a substituent represented by (50) in which o is 0; and R94c represents a group defined as a substituent present in a heterocyclic ring formed by linking R14 and R15 to each other and include a substituent represented by (28), (30) to (34), (39), (41), (45) ), (47), (54) to (58), (62) to (64), (66), (70), (79), (82) u (83), a substituent represented by (49) in which t is 1, or a substituent represented by (50) in which o is 0; a phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxy group and a lower alkylenedioxy group, a pyridyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxy group and a lower alkyl group which may have a hydroxyl group as a substituent, a pyrrolyl group which may have 1 to 3 lower alkyl groups as substituents on a pyrrolyl group, a benzoxazolyl group, a benzothiazolyl group, a furyl group, a lower alkyl group which may have a substituent selected from the group consisting of a hydroxy group and a halogen atom , a naphthyl group, a 1, 2, 3, 4-tetrahydronaphthyl group which may have 1 to 5 lower alkyl groups as substituents on the 1, 2, 3, 4-tetrahydronaphthalene ring, a quinolyl group, a 1, 2 group , 3-tetrazolyl which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group; a thiazolyl group which may have a phenyl group as a substituent on the thiazole ring; a benzoyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom, a piperidinyl group which may have a lower alkyl group as a substituent on the piperidine ring , a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, a 1,3,4-oxadiazolyl group which may have an oxo group as a substituent on the 1-ring. , 3,4-oxadiazole, a cycloalkyl group, a thienyl group or an imidazolyl group. The reaction of the compound (192) and the compound (183) is carried out under the same reaction conditions as in the reaction of the compound (30) and the compound (183) shown in the reaction formula 124 above. The reaction that converts the compound (193) into the compound (lqq) is carried out under the same reaction conditions as the reaction that converts the compound (184) to the compound (ljjjjjj) shown in reaction formula 124 above. The reaction of the compound (lqqqqq) and the compound (195) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. The compound (195), in which R94b is a group represented by (36) to (38), (43), (44), (53), (59), (60), (87), (88a) or (90a), is reacted with the compound (Iqq) in a suitable solvent in the presence of a copper halide such as copper iodide, an alkylglycine such as N, N-dimethylglycine and a metal alkyl phosphate such as potassium phosphate. Any solvent can be used herein as long as it is used in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The copper halide and alkyl glycine are used in a normal catalyst amount. The alkali metal phosphate is favorably used in a typical manner in at least an equimolar amount to the compound (lqq) and preferably 1 to 5 times to that of the compound (lqqqq) on a molar basis. The compound (195) is favorably used in an amount 0.5 to 5 times, and preferably 0.5 to 3 times, to that of the compound (lqq) on a molar basis. The reaction described above is typically carried out at room temperature at 200 ° C and preferably at about room temperature at 150 ° C and is completed in about 1 to 30 hours. The reaction of the compound (lqqqqq) and the co-tax (194) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The reaction of the compound (lqqqqqq) and the compound (196) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (5) of the formula 2 described above. [Reaction Formula 130] [Formula 231] (luuuuuu) (lvvvvvv) wherein Xx, Y, A, R2, R6, B22ar e and X2 are the same as those described above, and R10a 'represents a lower alkyl group. The reaction of the compound (luuuuuu) and the compound (197) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) of the reaction formula 2 above. [Reaction formula 131] [Formula 232] (lww ww) (lxxxxxx) where Xi, Y, A, R2, R6 and X2 are the same as those described above. R10b 'represents a lower alkyl group. The reaction of the compound (lwwwwww) and the compound (197a) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (4) shown in the reaction formula 2 above. [Reaction formula 132] [Formula 233] (l yyyyyy) (201) wherein R1, X1RY, X2, R2, Axo, R14a and R59b are the same as those described above, and R96 represents a piperazinyl group which may have, in the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group) and a lower alkyl pyridyl group. The reaction of the compound (198) and the compound (199) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The reaction that converts compound (200) to compound (201) can be carried out under the same reaction conditions as in hydrolysis B described in reaction formula 9 above. The reaction of the compound (201) and the compound (100 ') is carried out under the same reaction conditions as in the reaction of the compound (120b) and the compound (100') shown in the reaction formula 79 above. The reaction of the compound (201) and the compound (202) is carried out under the same reaction conditions as in the reaction of the compound (Ib) and the compound (6) shown in the reaction formula 2 above. The compound (200) can also be produced by the method shown in the following reaction formula 133: [Reaction formula 133] [Formula 234] (200b) wherein R74a, R2, X1 rY, A ?0, R59b and X2 are the same as those described above, and R14a 'represents a lower alkyl group which may have a hydroxyl group as a substituent. The reaction of the compound (200a) and the compound (203) is carried out under the same reaction conditions as in the reaction of the compound (2) and the compound (3) shown in the reaction formula 1 above. The compound (3) can also be produced by the method of the following reaction formula 134: [Formula Reaction 134] [Formula 235] wherein R80, A? 0, B23a, R14 and R15 are the same as those described above. The reaction that converts the compound (1081) to the compound (108m) is carried out under the same conditions of reaction than in the reaction that converts the compound (I) into the compound (Ig) shown in reaction formula 3 above. [Reaction Formula 135] [Formula 236] (lzzzzzz) (1AAAAAA) wherein R1, R2, Xx, Y, A? 0, B23a, R14 and R15 are the same as those described above. The reaction that converts the compound (lzzzzzz) into the compound (1AAAAAA) is carried out under the same reaction conditions as in the reaction that converts the compound (64b) to the compound (26a) shown in the reaction formula 89 above . A reaction mixture containing each of the target compounds obtained by the reaction formulas shown above is cooled, and subsequently a crude reaction product can be isolated from the reaction mixture cooled by an isolation operation such as filtration, concentration or extraction, and purified by a conventional purification operation such as column chromatography or recrystallization. The compound of the present invention represented by the general formula (1) includes a stereoisomer, an optical isomer, a solvate (hydrate and ethanolate, etc.). Of the compounds of the present invention, a compound having a basic group can be easily reacted with a conventional pharmacologically acceptable acid to form a salt. Examples of this acid include mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid and phosphoric acid, and organic acids such as methanesulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, masonic acid and lactic acid. Of the compounds of the present invention, a compound having an acid group can be easily reacted with a conventional pharmacologically acceptable basic compound to form a salt. Examples of this basic co-salt include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate. Next, a medical formulation containing a compound according to the present invention as an active ingredient will be described. The medical formulation is obtained by formulating a compound according to the present invention in the form of a pharmaceutical preparation, and more specifically, prepared using a diluent or excipient such as a filler, expander, binder, humectant, disintegrant, surfactant or lubricant. The form of this medicinal formulation can be selected in various ways depending on the therapeutic purpose, and the physical forms include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories and injections (liquids, suspensions). The carrier that will be used to form the tablets can be broadly selected from those conventionally known. Examples of the carrier include excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin and crystalline cellulose, binders such as water, ethanol, propanol, simple syrup, a glucose solution, a solution of starch, a solution of gelatin, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate and polyvinylpyrrolidone, disintegrants such as dry starch, sodium arginate, powdered agar, powder laminating, sodium bicarbonate, calcium carbonate, fatty acid ester polyoxyethylene sorbitan, sodium lauryl sulfate, stearic monoglyceride, starch and lactose, anti-disintegrants such as sucrose, stearin, cocoa butter and hydrogenated oil, sorbents such as quaternary ammonium base and sodium lauplsulfate, wetting agents such as glycerol and starch, adsorbents such such as starch, lactose, kaolin, bentonite and colloidal silicate and lubricants such as purified talc, stearate, boric acid powder and polyethylene glycol. In addition, the tablets can be coated in a conventional manner as required. Examples of coated tablets include sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets or double or multilayer tablets. The carriers that will be used to form pills can be broadly selected from those conventionally known. Examples of the carrier include excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin and talc, binders such as gum arabic powder, tragacanth powder, gelatin and ethanol, and disintegrants such as laminarán and agar. The carriers that will be used to form suppositories can be broadly selected from those conventionally known. Examples of the carrier include polyethylene glycol, cocoa butter, higher alcohols, esters of higher alcohols, gelatin and semi-synthetic glycerides. When liquids, emulsions and suspensions are prepared as injection preparations, they are sterilized and preferably controlled to be isotonic with the blood.

The diluents that will be used to form these liquid preparations, emulsion and suspension can be broadly selected from those conventionally known. Examples of the diluents include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol and polyoxyethylene sorbitan fatty acid ester. In this case, the medical formulations may contain sodium chloride, glucose or glycerol in an amount sufficient to prepare isotonic solutions. Likewise, solubilizers, pH regulators, conventional analgesics and the like, and, as necessary, coloring agents, preservatives, spices, flavors, sweeteners and the like, or other pharmaceuticals can be contained. Although the amount of a compound according to the present invention contained in a medical formulation is not particularly limited and can be suitably selected from a wide range of compounds. It is preferable that a compound according to the present invention be contained in an amount of 1 to 70% by weight in a medical formulation. The method for administering a medical formulation according to the present invention is not particularly mimicked. The medical formulation can be administered by a method determined in the form of the medical formulation, the age of the patient, sex, severity of the disease and other conditions. For example, tablets, pills, Liquids, suspensions, emulsions, granules and capsules are administered orally. Formulations for injection are administered individually or by mixing with a conventional fluid replacement such a glucose solution or amino acid solution, intravenously or, as necessary, administered individually in intramuscular, intradermal, subcutaneous or intraperitoneal form. Suppositories are administered to the rectum. The dose for the medical formulation mentioned above can be suitably selected depending on the use, age of the patient, sex and severity of the disease and other conditions. Typically, 0.001 to 100 mg per kg (body weight) per day, preferably 0.001 to 50 mg per kg (body weight) per day, is administered once or several times a day. Since the doses described above vary depending on varying conditions, the dose may be smaller than the lower limit of the scale described above or greater than the upper limit of the scale described above. The medicinal drug has an excellent antineoplastic effect and thus a therapeutic drug against tumors is useful. As a tumor in which an antineoplastic effect is exerted, for example, a malignant tumor and the like may be mentioned. Like this malignant tumor, for example, it can be mention a solid tumor (cancer, sarcoma and the like), blood cancers (lymphoma, leukemia, myeloma and the like). Specific examples of the malignant tumor include brain tumors of a child such as astroglioma, malignant medulloblastoma, germ cell tumor, craniopharyngioma and ependymoma; adult brain tumors such as glioma, meningiora, pituitary gland adenoma and neurilema; cancers of the cervix of the head such as maxillary sinus cancer, pharyngeal cancer (nasopharyngeal carcinoma), mesopharyngeal carcinoma, hypopharyngeal carcinoma), laryngeal cancer, oral cavity cancer, lip cancer, tongue cancer and parotid cancer; cancers and breast tumors, such as small cell lung cancer, non-small cell lung cancer, breast adenoma and mesotheliomas; cancers and tumors of digestive organs such as esophageal cancer, liver cancer, primary liver cancer, gallbladder cancer, bile duct cancer, stomach cancer, colon cancer, colon cancer, rectal cancer, anal cancer, pancreatic cancer and tumor of internal secretion of the pancreas; cancers of urinary organs and tumors such as penile cancer, pelvic renal / urethral cancer, renal cell cancer, testicular tumor, prostate cancer, bladder cancer, ilm tumor and urothelial cancer; gynecologic cancers and tumors such as cancer vulvar; cancer of the uterine cervix, cancer of the body of the uterus, endometrial cancer, uterine sarcoma, choriooma, vaginal cancer, breast cancer, ovarian cancer, ovarian germ cell tumor; a soft tissue sarcoma of a child and adult; bone tumors such as osteosarcoma and Swing tumor; cancers and tumors of endocrine tissue such as aortecortical cancer, thyroid cancer; malignant lymphoma and leukemia such as malignant lymphoma, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, plasmacytic tumor, acute myelogenous leukemia, acute lymphatic leukemia, adult T-cell leukemia lymphoma, chronic myelogenous leukemia and chronic lymphatic leukemia; cancers and skin tumors such as chronic myeloproliferative disorders, malignant melanoma, spiny cell cancer, basal cell cancer and mycosis fungoides; and metastatic foci of tumors and cancers mentioned above. Of these, the medicinal drug of the present invention has an effect on liver cancer, chronic myelogenous leukemia, acute myelogenous leukemia, lymphoma and multiple myeloma. The medicinal drug of the present invention has fewer side effects and excellent safety and is then more excellent tumor therapeutic agent.

DETAILED DESCRIPTION OF THE INVENTION The present invention will be explained more specifically by way of reference examples, examples, preparation examples and pharmacological tests. Reference Example 1 Production of 1- (t-butoxycarbonyl) -A- (4-hydroxyphenyl) -1,2,5,6-tetrahydropyridine (Step 1) Production of 1- (t-butoxycarbonyl) -A - [(4-methoxyraethoxy) phenyl] -4-hydroxypiperidine A solution of 1-bromo-4-methoxymethoxybenzene (5.43 g, 25.0 mmol) in tetrahydrofuran (THF) (100 mL) was stirred at -85 ° C, and a solution of 2.46 M n-butyllithium hexane (10.2 mL, 25.0 mmol) was added dropwise to the stirred solution for 10 minutes. The resulting solution was stirred at the temperature for 40 minutes. To the reaction solution was added dropwise over 10 minutes a solution of 1- (t-butoxycarbonyl) -piperidone (5.20 g, 26.0 mmol) in THF (30 mL). The temperature of the resulting solution was raised to -25 ° C for 4 hours, and then the solution was stirred at that temperature for 2 hours. An aqueous solution of saturated ammonium chloride was then added to this solution. The reaction solution was extracted with ethyl acetate and dried over anhydrous magnesium sulfate, after which the solvent was evaporated. The residue was purified by column chromatography on silica gel (ethyl acetate: n-hexane = 2: 3, in proportion by volume; hereinafter the same), thereby producing 7.63 g of the title compound. Appearance: Colorless oil XH NMR (CDC13) d 1.49 (9H, s), 1.73 (2H, d, J = 12.0 Hz), 1.97 (2H, brs), 3.24 (2H, brs), 3.48 (3H, s), 4.00 (2H, brs), . 17 (2H, s), 7.03 (2H, d, J = 9.0 Hz), 7.39 (2H, d, J = 9.0 Hz).

(Step 2) Production of 1- (t-butoxycarbonyl) - A - (4-hydroxyphenyl) -1,2,5,6-tetrahydropyridine To a solution of 1- (t-butoxycarbonyl) -4- [(4-methoxymethoxy) ) phenyl] -4-hydroxypiperidine (5.32 g, 15.8 ramol) in toluene (100 mL) was added p-toluenesulfonic acid monohydrate (0.56 g, 2.95 mmol), and the resulting solution was refluxed for 21 hours. The reaction solution was cooled to room temperature, and evaporated under reduced pressure. To this crude product was added ethanol (60 mL) and 2 M hydrochloric acid (40 mL, 80 mmol), and the resulting solution was stirred for 2 hours at 60 ° C. The reaction solution was cooled again to room temperature, and evaporated under reduced pressure. Methanol (100 mL), triethylamine (9.0 mL, 64.6 ramol) and di-t-butyl dicarbonate (5.20 g, 23.8 mmol) were added to the residue, and the resulting solution was stirred for 24 hours at room temperature. The solvent was evaporated under reduced pressure, after which 100 mL of ethyl acetate was added to the residue. The insoluble matter was removed by filtration, after which the filtrate was evaporated under reduced pressure. To the residue was added 1,4-dioxane (50 mL) and a 1 M aqueous solution of sodium hydroxide (50 mL, 50 mmol) and stirred for 14 hours at 60 ° C. To the resulting reaction solution was added at room temperature 2M hydrochloric acid (25, 50 mmol) to neutralize, and then extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated to thereby yield 4.10 g of the title compound. Appearance: Amorphous coffee XH RNM (CDC13) d 1.49 (9H, s), 2.47 (2H, brs), 3.62 (2H, t, J = 5.5 Hz), 4.05 (2H, brs), 5.91 (1H, brs), 6.81 (2H, d, J = 9.0 Hz), 7.25 (2H, d, J = 9.0 Hz). Reference Example 2 Production of methyl 5- (4-benzylpiperazin-1-yl) -2-ethoxyramethoxybenzoate To a solution of methyl 5-chloro-2-methoxymethoxybenzoate (1.45 g, 6.29 rpmol) and 1-benzylpiperazine (1.66 g) , 9.43 mmol) in toluene (50 mL) were added palladium acetate (28 mg, 0.126 ramol), 2,2'-bis (diphenylphosphino) -1, 1-binaphthyl (157 mg, 0.252 mmol) and cesium carbonate. (3.07 g, 9.43 mmol), and the resulting solution was refluxed for 3 hours. Water was added to the resulting solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 2), thereby producing 400 mg of the Title. Appearance: Yellow oil XH NMR (CDCI3) d 2.59-2.62 (4H, m), 3.12-3.16 (4H, m), 3.51 (3H, s), 3.57 (2H, s), 3.88 (3H, s), 5.16 (2H, s), 7.01 (1H, dd, J = 9.1 Hz, 3.1 Hz), 7.10 (1H, d, J = 9.1 Hz), 7.28-7.35 (6H, m). The following compounds were produced in the same manner as in Reference Example 2.

Table 1 • Table 2 Reference Example 14 Production of 5- (4-benzylpiperazin-1-yl) -2-hydroxybenzoate of raethyl To a solution of 400 mq of methyl 5- (4-benzylpiperazin-1-yl) -2-methoxymethoxybenzoate (1.1 mmol ) in 1,4-dioxane (20 mL) was added a solution of 4 N hydroquin chloride in 1,4-dioxane (4 mL, 16 mmol), and the resulting solution was added for 2 hours at 100 ° C. The resulting reaction solution was subjected to distillation under reduced pressure to obtain a residue. This residue was purified by column chromatography on silica gel (dichloromethane: methanol = 30: 1), thereby producing 353 mq of the title compound. Appearance: Pale yellow powder XH RNM (CD3OD) d 3.29-3.40 (8H, ra), 3.94 (3H, s), 4.39 (2H, s), 6.91 (1H, d, J = 8.9 Hz), 7.28 (1H, dd, J = 8.9 Hz, 3.0 Hz), 7.42 (1H, d, J = 3.0 Hz), 7.49-7.60 (5H, m). The following compounds were produced in the same manner as in Reference Example 14.

Table 3 Reference Example 20 Production of ethyl N- (-hydroxyphenyl) isonipecotate To a solution of ethyl N- (4-methoxyphenyl) -isonipecotate (2.63 g, 10 mmol) in dichloromethane (100 mL) was added a tribromide solution of 2 M boron in dichloromethane (20 mL, 40 mmol), and the resulting solution was added for 0.5 hour at room temperature. The resulting reaction solution was poured into ice water, then an aqueous solution of 1 M sodium hydroxide (110 mL) was added to the solution. After depositing, the resulting solution was separated. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to thereby yield 2.43 g of the title compound. Appearance: Yellow oil VH RNM (CDC13) d 1.27 (3H, t, J = 7.0 Hz), 1.91 (2H, m), 2.02 (2H, brd, J = 11.5 Hz), 2.38 (1H, m), 2.68 (2H, dt, J = 2.0 Hz, 11.5 Hz), 3.46 (2H, dt, J = 12.0 Hz, 3.0 Hz ), 4.16 (2H, q, J = 7.0 Hz), 4.45 (1H, brs), 6.75 (2H, d, J = 9.0 Hz), 6.86 (2H, d, J = 9.0 Hz). The following compounds were produced in the same manner as in Reference Example 20.

Reference Example 21 4- (2-Fluoro-4-nitrophenoxy) phenol Vi RNM (DMSO-d6) d 6.80-7.10 (5H, m), 8.04 (1H, ddd, J = 1.4 Hz, 2.7 Hz, 9.2 Hz), 8.29 (1H, dd, J = 2.7 Hz, 10.9 Hz), 9.59 (1H, s).

Reference Example 22 l-Benzyl-3- (4-hydroxyphenyl)-iraidazolidin-2-one XH NMR (DMSO-d6) d 3.18-3.40 (2H, m), 3.61-3.80 (2H, m), 4. 35 (2H, s), 6.71 (2H, d, J = 8.8 Hz), 7.15-7.48 (7H, ra), 9.10 (1H, s).

Reference Example 23 Production of 2- (4-hydroxy-3-ylamino) -1- (4-piperonylpiperazin-1-yl) ethanone To a solution of N- (4-hydroxy-enyl) -lucine (11.38 g, 68.1 mmol) in N, N-dimethyl ormamide (DMF) (150 mL) were added under ice cooling 1-piperonylpiperazine (15.0 g, 68.1 mmol), monohydrate 1-hydroxybenzotriazole (10.43 g, 68.1 mmol) and l-ethyl-3- (3-diraethylaminopropyl) carbodiimide hydrochloride (15.66) q, 81.7 mmol), and the resulting solution was added for 30 minutes under cooling with ice and for 4.5 hours at room temperature. The reaction solution was concentrated under reduced pressure. A solution of saturated sodium bicarbonate (400 mL) was added to the residue, and extracted with ethyl acetate (400 mL). The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to leave the resulting product solidified in a powder form. Ethyl acetate was added, and the resulting product was filtered and washed with ethyl acetate, thereby yielding 18.58 g of the title compound. Appearance: Brown powder? H NMR (DMSO-d6) d 2.30 (2H, brs), 2.36 (2H, brs), 3.40 (2H, s), 3. 47 (4H, t, J = 14.5 Hz), 4.03 (2H, d, J = 7.0 Hz), 4.90 (1H, brs), 5.99 (2H, s), 6.49 (2H, d, J = 8.9 Hz), 6.54 (2H, d, J = 8.9 Hz), 6.75 (1H, dd, J = 8.0 Hz, 1.1 Hz), 6.85 (1H, d, J = 8.0 Hz), 6.87 (1H, s), 8.42 (1H, s). The following compounds were produced in the same manner as in Reference Example 23.

Reference Example 24 6-Chloro-N- (3,4-dichlorofenyl) nicotinaraide? U NRN (CDC13) d 7.64 (1H, d, J = 8.9 Hz), 7.72 (1H, dd, J = 8.7 Hz, 2.3 Hz), 7.73 (1H, dd, J = 8.3 Hz, 0.7 Hz), 8.12 (1H, d, J = 2.3 Hz), 8.35 (1H, dd, J = 8.3 Hz, 2.5 Hz), 8. 95 (1H, dd, J = 2.5 Hz, 0.7 Hz), 10.71 (1H, brs).

Reference Example 25 4- (4-Piperonylpiperazine-1-carbonyl) -1- (4-hydroxyphenyl) pyrrolidin-2-one? NMR (CDC13) d 2.43-2.45 (4H, m), 2.73-2.95 (2H, m), 3.45 (2H, s), 3.49-3.54 (4H, m), 3.65-3.72 (1H, m), 3.78- 3.87 (1H, m), 4.17-4.23 (1H, m), 5.96 (2H, s), 6.71-6.80 (4H, m), 6.84-6.85 (1H, m), 7.29 (2H, d, J = 8.9 Hz).

Table 4 Reference Example 35 Production of Ethyl (4-hydroxy-3-methylphenylamino) acetate. Potassium carbonate (5.04 g, 36.5 mmol) was added at room temperature to a solution of 4-amino-o-cresol (3.00 g, 24.4 mmol. ) and ethyl bromoacetate (2.70 mL, 24.4 mmol) in DMF (30 mL). The resulting solution was added at room temperature for 1.5 hours. Aqua was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with brine. The acetate layer ethyl was dried over anhydrous sodium sulfate, and evaporated. The residue was purified by column chromatography over silica gel (n-hexane: ethyl acetate = 3: 1), thereby producing 5.10 q of the title compound. Appearance: Yellow solid? U RNM (CDC13) d 1.28 (3H, t, J = 7.1 Hz), 2.19 (3H, s), 3.84 (2H, s), 3.95 (1H, brs), 4.22 (2H, q, J = 7.1 Hz), 4.59 (1H, brs), 6.36 (1H, dd, J = 8.4 Hz, 2.9 Hz), 6.44 (1H, d, J = 2.9 Hz), 6.63 (1H, d, J = 8.4 Hz ). The following compounds were produced in the same manner as in Reference Example 35.

Reference Example 36 (3-hydroxyphenylamino) ethyl acetate XH NMR (CDCl 3) d 1.30 (3H, t, J = 7.1 Hz), 3.88 (2H, s), 4.25 (2H, q, J = 7.1 Hz), 4.29 (1H, brs), 4.85 (1H, s), 6.08-6.10 (1H, m), 6.18-6.24 (2H, m), 7.01-7.0 (1H, m).

Reference Example 37 (benzyl 4-hydroxy-3-methoxyphenylamino) acetate, U RNM (CDCl 3) d 3.8 K 3 H, s), 3.92 (2 H, brs), 4.01 (1 H, brs), 5.09 (1 H, brs), 5.20 (2H, s), 6.11 (1H, dd, J = 8.4 Hz, 2.6 Hz), 6.23 (1H, d, J = 2.6 Hz), 6.76 (1H, d, J = 8.4 Hz), 7.31-7.38 ( 5H, m).

Reference Example 38 [3- (4-Benzyloxy-3-phenylphenyl) -2-oxotetrahydro-pyrimidin-1-yl] t-butyl acetate? U NRM (CDC13) d 1.47 (9H, s), 2.04-2.21 (2H , m), 2.25 (3H, s), 3.45 (2H, t, J = 5.9 Hz), 3.67 (2H, t, J = 5.9 Hz), 4.04 (2H, s), 5.06 (2H, s), 6.82 (1H, d, J = 8.6 Hz), 7.01 (1H, dd, J = 2.6 Hz, 8.6 Hz), 7.06-7.12 (1H, m), 7.26-7. 8 (5H, m).

Table 5 Table 6 Table 7 (Ph stands for a benzene ring having 1 to 4 free valences, hereinafter in the present Ph indicates the same meaning).

Reference Example 58 (t-butyl) 3-cyano-4-hydroxyphenylamino) acetate MS 248 (M +).

Reference Example 59 Production of 2- [4- (2-fluoro-4-nitrophenoxy) phenoxy] -1- (-piperonylpiperazin-1-yl) ethanone Potassium carbonate (0.350 g, 2.53 mmol) was added to a solution of 4- (2-fluoro-4-nitrophenoxy) phenol (0.420 g, 1.69 mmol) and l-chloroacetyl-4-piperonylpiperazine (0.500 g, 1.70 mmol) in DMF (8 mL). The resulting reaction mixture was stirred for 40 minutes at 100 ° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated, thereby yielding 0.860 of the title compound. Appearance: Brown oil? U RNM (CDC13) d 2.50-2.60 (4H, m), 3.43 (2H, s), 3.50-3.70 (4H, m), 4.71 (2H, s), 5.95 (2H, s), 6.65-6.75 (2H, m), 6.80-7.05 (6H, m), 7.94 (1H, dd, J = 2.3 Hz, 9.1 Hz), 8.06 (1H, dd, J = 2.3 Hz, 10.4 Hz).

The following compound was produced in the same manner as in Reference Example 59.

Reference Example 60 2- [4- (2-Fluoro-4-nitrophenoxy) phenylamino] -1- (4-piperonylpiperazin-1-yl) ethanone XH NMR (DMS0-d6) d 2.25-2. A 0 (4H, m), 3.43 (2H, s), 3.45-3.50 (4H, m), 3.90 (2H, d, J = 5.1 Hz), 5.75 (1H, t, J = 5.1 Hz), 5.99 (2H, s), 6.70-6.75 (3H, m), 6.80-7.00 (5H, m), 8.05 (1H, ddd, J = 1.4 Hz, 2.7 Hz, 10.5 Hz), 8.27 (1H, dd, J = 2.7 Hz, 11. 0 Hz).

Reference Example 61 Production of methyl 3- (4-benzyloxyphenylamino) -propionate Under nitrogen, 4-benzyloxyaniline (13.0 g, 65 mmol) was dissolved on heating at 70 ° C, and a complex of diethyl ether-boron trifluoride ( 0.82 mL, 6.5 mmol) was added dropwise at the same temperature to the dissolved solution. Methyl acrylate (5.85 mL, 65 mmol) was slowly added dropwise to the resulting solution. This solution was stirred for 10 hours at 70 ° C. After cooling with ice, ethyl acetate was added to the reaction mixture and washed with 1 N aqueous sodium hydroxide and brine. The organic layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 5: 1), thereby producing 17.5 g of the composed of the title.

Appearance: Brown powder Vi RNM (CDCI3) d 2.60 (2H, t, J = 6.4 Hz), 3.39 (2H, t, J = 6.4 Hz), 3.69 (3H, s), 3.77 (1H, brs), 4.98 ( 2H, s), 6.58 (2H, d, J = 8.9 Hz), 6.85 (2H, d, J = 8.9 Hz), 7.30-7.44 (5H, m).

Reference Example 62 Production of Ethyl 3- (4-methoxyphenylamino) propionate 3- (-hydroxyphenylamino) propionic acid (4.00 g, 20.5 mmol) was added to 48% hydrobromic acid (50 mL), and the resulting solution was stirred for 2.5 hours at 100 ° C. After concentration under reduced pressure, ethanol (10 mL) was added to the residue, and concentrated under reduced pressure. A solution of saturated sodium bicarbonate was added to the residue, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 2: 1), to thereby produce 1.27 g of the title compound. Appearance: Yellow oil 1U RNM (CDCI3) d 1.27 (3H, t, J = 7.2 Hz), 2.59 (2H, t, J = 6.4 Hz), 3.38 (2H, t, J = 6.4 Hz), 4.15 (2H, q, J = 7.2 Hz), 6.55 (2H, d, J = 8.8 Hz), 6.70 (2H, d, J = 8.8 Hz).

Reference Example 63 Production of ethyl [(3-fluoro-4-hydroxyphenyl) methylamino] acetate. (3-Fluoro-4-hydroxyphenylamino) ethyl acetate (1.06 g, 5.1 mmol) was dissolved in methanol (150 mL) and the The resulting solution was cooled with ice. To the resulting solution were added 37% aqueous formaldehyde (1.5 mL), sodium triacetoxyborohydride (1 g, 16 mmol) and acetic acid (0.9 mL, 15 mmol), and then stirred at room temperature under nitrogen atmosphere for 14 hours. The solvent was evaporated under reduced pressure. Water was added to the residue, and the resulting solution was neutralized with a saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 2), to thereby yield 0.93 g of the title compound. Appearance: Light brown oil XH RNM (CDC13) d 1.24 (3H, t, J = 7.1 Hz), 3.00 (3H, s), 3.98 (2H, s), 4.17 (2H, q, J = 7.1 Hz), 4.68 (1H, brs), 6.31-6.52 (2H, m), 6.87 (1H, t, J = 8.9 Hz). The following compounds were produced in the same manner as in Reference Example 63.

Reference Example 64 (Methyl. {4- [5- (4-trifluoromethylbenzyl) pyridin-2-yloxy] phenyl} amino) ethyl acetate? U NRM (CDC13) d 1.25 (3H, t, J = 7.1 Hz), 3.07 (3H, s), 3.95 (2H, s), 4.04 (2H, s), 4.18 (2H, q, J = 7.1 Hz), 6.69 (2H, d, J = 9.1 Hz), 6.75 ( 1H, d, J = 8.5 Hz), 7.00 (2H, d, J = 9.1 Hz), 7.27 (2H, d, J = 8.1 Hz), 7.39 (1H, dd, J = 8.5 Hz, 2.5 Hz), 7.54 (2H, d, J = 8.1 Hz), 8.04 (1H, d, J = 2.5 Hz).

Reference Example 65 [(4-Hydroxy-2-trifluoromethylphenyl) methylamino] -acetic acid MS 277 (M +).

Table 8 R (M means the number of methylene groups, hereinafter M indicates the meaning misrao).

Table 9 Reference Example 77 Production of 1- (4-piperonylpiperazin-1-yl) -2- [cyclopropyl (4-hydroxyphenyl) amino] ethanone To a solution of 1- (4-piperonylpiperazin-1-yl) -2- (4 -hydroxy phenylamino) ethanone (1.00 g, 2.7 mmol) in methanol (10 mL) were added acetic acid (1.55 mL, 27 mmol), 3A1 / 16 molecular sieves (1.00 g), [(1-ethoxycyclopropyl) oxy] trimethylsilane (0.653 mL, 3.2 mmol) and sodium cyanoborohydride (770 mg, 12 mmol). The resulting solution is stirred for 16 hours at 60 ° C. This reaction solution was filtered and concentrated, and to the residue were added ethyl acetate and water. The aqueous layer was adjusted to pH 10 using 6 N aqueous sodium hydroxide. This layer was stirred for some time, and once the insoluble matter had been dissolved, the ethyl acetate layer was removed, and washed with hydroxide. aqueous sodium 2 N and a saturated sodium bicarbonate solution, then dried over anhydrous magnesium sulfate. The solvent was evaporated, in order to produce 770 mg of the title compound. Appearance: White XH RNM powder (CDC13) d 0.54-0.59 (2H, m), 0.72-0.79 (2H, m), 2.39-2.45 (4H, m), 2.70-2.77 (1H, m), 3.44 (2H, s), 3.48-3.51 (2H, m), 3.57-3.60 (2H, m), 4.12 (2H, s), 5.95 (2H, s), 6.62-6.67 (2H, m), 6.74-6.85 (5H, ra). The following compound was produced in the same manner as in Reference Example 77.

Reference Example 78. { Cyclopropyl [3-phenyl-4- (5-nitropyridin-2-yloxy) phenyl] amino} ethyl acetate lU NMR (CDCI3) d 0.66-0.72 (2H, m), 0.83-0.89 (2H, m), 1.26 (3H, t, J = 7.3 Hz), 2.10 (3H, s), 2.71-2.79 ( 1H, m), 4.08-4.22 (4H, m), 6.77-6.82 (2H, m), 6.91-6.95 (2H, m), 8.40-8.45 (1H, m), 9.05 (1H, d, J = 2.8 Hz).

Reference Example 79 Production of [(3-hydroxyphenyl) -Rethylaraine] -ethyl acetate. Potassium bicarbonate (1.42 mL, 14.19 Rmol) was added to a solution of ethyl (3-hydroxyphenylamino) acetate (2.77 g, 14.19 mmol) in DMF (15 mL). To the resulting solution was added methyl iodide iodide (1.77 mL, 28.38 mmol), and then stirred at room temperature for 18 hours. To the resulting reaction solution was added brine (150 mL), and the obtained mixture was extracted with ethyl acetate (150 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate, after which solvent was evaporated, thereby yielding 2.48 g of the title compound. Appearance: Pale yellow oil XH RNM (CDC13) d 1.24 (3H, t, J = 7.1 Hz), 3.04 (3H, s), 4.03 (2H, s), 4.18 (2H, q, J = 7.1 Hz), 5.17 (1H, brs), 6.17-6.27 (3H, m), 7.04-7.10 (1H, m). The following compounds were produced in the same manner as in Reference Example 79.

Table 10 Table 11 Table 12 Reference Example R137 Rl38 Rl39 Xa3 Xa4? RNM (CDCI3) dppm No 2.44 (8H, brs), 2.96 (2H, s), 3.30 (3H, s), 3.38 (2H, s), 5.92 (2H, s), 6.72 (2H, brs), 6.82 (1H, s), 7.09 (1H, d, J = 95"-H Piperonil none -CH2- 9.1 Hz), 7.20 (2H, d, J = 8.9 Hz), 7.29 (2H, d, J = 8.9 Hz), 8.51 (1H, dd, J = 9.1 Hz, 2.8 Hz ), 9.04 (1H, d, J = 2.8 Hz).

Table 13 Reference Example 100 Production of ethyl [acetyl (3-fluoro-4-hydroxyphenyl) amino] acetate [3-Fluoro-4-hydroxyphenylamino] ethyl acetate (0.84 g, 4 mmol) was dissolved in N, N-dimethylacetamide ( 4 mL). To the resulting solution was added acetyl chloride (0.6 mL, 10 mmol), and the resulting solution was stirred at room temperature for 1 hour. Water (1 mL), methanol was added (10 mL) and saturated sodium carbonate (10 mL), and the mixture was stirred at room temperature for 1 hour. Water was added to the solution. 10% hydrochloric acid was used to render the acid solution, and then the solution was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by column chromatography on silica gel (ethyl acetate: n-hexane = 2: 1), thereby yielding 0.84 g of the title compound. Appearance: Colorless powder XH RNM (CDC13) d 1.28 (3H, t, J = 7.3 Hz), 1.94 (3H, s), 4.20 (2H, q, J = 7.3 Hz), 4.32 (2H, s), 6.02 ( 1H, brs), 6.99-7.07 (2H, m), 7.13-7.18 (1H, m). The following compounds were produced in the same manner as in Reference Example 100.

Table 14 Table 15 Table 16 Reference Example 110 Production of (6-chloropyridin-3-yl) 4-trifluoromethylphenyl) methanone Under a flow of argon gas, half a solution of trifluoride of 4-bromobenzo (1.20 g, 5.33 mmol) in THF (6 mL ) was added to magnesium (156 mg, 6.41 mmol). The resulting solution was stirred, and additional 1,2-dibromoethane (3 drops) was added. Once the reaction started, the balance of 4-bromobenzo trifluoride in THF solution was added dropwise, and once the drop was complete, the resulting solution was stirred for 30 minutes at 60 ° C. A solution of 6-chloro-N-met oxy-N-met inicot inamide (990 mg, 5.36 mraol) in THF (3 mL) was charged into a separate reaction vessel, within which the above reaction solution was added. by dripping under a flow of argon gas and cooled with ice. After the trickling ended, the resulting solution was stirred for 30 minutes at room temperature, and then heated to reflux for 1 hour. The reaction solution was cooled with ice, then aqueous ammonium chloride and water were added. The resulting solution was extracted with ethyl acetate, and washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (n-hexane ethyl acetate = 10: 1), to thereby produce 610 mg of the title corapuesto. Appearance: White powder XH RNM (CDC13) d 7.52 (1H, d, J = 8.3 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.90 (2H, d, J = 8.0 Hz), 8.11 (1H, dd, J = 8.3 Hz, 2.0 Hz), 8.77 (1H, d, J = 2.0 Hz).

Reference Example 111 Production of Ethyl 3- [4- (4-nitrophenoxy) phenyl] -propionate To a solution of ethyl 3- (4-hydroxyphenyl) -propionate (6.00 g, 30.9 mmol) in DMF (60 mL) 4-fluoronitrobenzene (6.54 g, 46.3 mmol) and potassium carbonate were added (5.12 g, 37.1 mmol). The resulting reaction solution was stirred for 1 hour at 80 ° C. Water was added to the reaction solution and extracted with ethyl acetate. The resulting ethyl acetate layer was washed with water and then with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 5: 1), thereby producing 9.64 g of the title compound. Appearance: Pale yellow oil? U RNM (CDC13) d 1.23 (3H, t, J = 7.1 Hz), 2.62 (2H, t, J = 7.7 Hz), 2.96 (2H, t, J = 7.7 Hz), 4.12 ( 2H, q, J = 7.1 Hz), 6.93-7.06 (4H, m), 7.24 (2H, d, J = 8.5 Hz), 8.17 (2H, d, J = 9.2 Hz). The following compounds were produced in the same manner as in Reference Template 111.

Table 17 (Ac means an acetyl group, hereinafter, Ac indicates the same meaning).

Table 18 Table 19 Table 20 Table 21 Table 22 Table 23 20 Table 24 fifteen twenty Table 25 Table 26 51 Table 26 Table 27 Table 28 20 Table 29 Table 30 (CHOPh means a formylphenyl group, henceforth, CHOPh indicates the meaning misrao).

Table 31 15 20 Table 32 25 Table 33 twenty Table 34 Reference Example 247 Production of 4- (5-nitropyridin-2-yloxy) phenylaraine To a solution of sodium hydroxide (730 mg, 18. 25 mmol) in methanol was added 4-aminophenol (2.00 g, 18.32 mmol). After it was made to dissolve the resulting mixture, methanol was evaporated under reduced pressure. DMF (20 mL) was added to the residue, and then 2-chloro-5-ni t-ropyridine (2.91 g, 18.35 mmol). The reaction solution was stirred for 1.5 hours at 70 ° C, and then concentrated under reduced pressure. Water was added to the residue, and the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with saltwater. The ethyl acetate layer was dried over anhydrous magnesium sulfate, after which solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 1), with which to produce 3.37 g of the compound of Title . Appearance: Dark red powder XH RNM (DMSO-d6) d 5.10 (2H, s), 6.61 (2H, d, J = 8.9 Hz), 6.85 (2H, d, J = 8.9 Hz), 7.08 (1H, d, J = 9.0 Hz), 8.55 (1H, dd, J = 9.0 Hz, 3.0 Hz), 9.01 (1H, d, J = 3.0 Hz).

The following compounds were produced in the same manner as in Reference Example 247.

Table 35 Table 36 Reference Example 254 Production of ethyl 3- [4- (3-nitrophenoxy) phenyl] -propionate Under argon, to a solution of 3-iodonitrobenzene (3.00 g, 12.0 mmol) in pyridine (15 mL) were added 3- ( 4-hydroxyphenyl) propionate (2.81 g, 14.5 mmol), copper oxide (3.35 g, 42.2 mmol), and potassium carbonate (4.16 g, 30.1 mmol), and the resulting solution was refluxed for 40 hours. The reaction solution was concentrated under reduced pressure. Water and ethyl acetate were added to the residue, and once the insoluble matter had been filtered, and the filtrate was extracted with ethyl acetate. The ethyl acetate layer was washed with 1 M hydrochloric acid, water and a saturated sodium bicarbonate solution, and then washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 9: 1 -> 6: 1), thereby producing 1.12 g of the title compound. Appearance: Pale yellow oil? U RNM (CDC13) d 1.23 (3H, t, J = 7.1 Hz), 2.62 (2H, t, J = 7.7 Hz), 2.95 (2H, t, J = 7.7 Hz), 4.12 ( 2H, q, J = 7.1 Hz), 6. 96 (2H, d, J = 8.6 Hz), 7.22 (2H, d, J = 8.6 Hz), 7.29 (1H, dd, J = 8.2 Hz, 2.3 Hz), 7.43 (1H, t, J = 8.2 Hz), 7.74 (1H, s), 7. 90 (1H, dd, J = 8.2 Hz, 2.3 Hz).

Reference Example 255 Production of 1- (t-butoxycarbonyl) -A - [A - (4-nitrophenoxy) phenyl] piperazine Potassium carbonate (15.7 g, 114 mmol) was added to a solution of 2-chloro-5-nitropyridine (4.50 g, 28.4 mmol) and 1- (4-hydroxyphenyl) piperazine dihydrochloride (7.13 g, 28.4 mmol) in DMF (80 mL). The resulting solution was stirred at room temperature for 8 hours. To this reaction solution was added di-t-butyl dicarbonate (6.81 g, 31.2 mmol), and stirred at room temperature for 2.5 days. The reaction solution was charged with ethyl acetate, washed with water, and dried with anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 1: 3), thereby producing 7.05 g of the title compound. Appearance: Yellow needles V? NMR (CDCI3) d 1.49 (9H, s), 3.15 (4H, t, J = 5.0 Hz), 3.59 (4H, t, J = 5.0 Hz), 6.98 (2H, d, J = 9.0 Hz), 7.00 ( 1H, d, J = 9.0 Hz), 7.07 (2H, d, J = 9.0 Hz), 8.45 (1H, dd, J = 9.0 Hz, 2.5 Hz), 9.05 (1H, d, J = 2.5 Hz).

Reference Example 256 Production of (ethyl. {3-methoxy-4- [5- (4-trifluoromethylphenylcarbamoyl) pyridin-2-yloxy] phenyl} araino) acetate [ethyl (4-hydroxy-3-methoxyphenyl) was dissolved ) amino] benzyl acetate (9.46 g), 30 ramol) and 6-chloro-N- (4-trifluoromethylphenyl) nicotinamide (9.02 g, 30 mmol) in DMF (100 mL). To the resulting solution was added potassium carbonate (6.22 g, 45 ramol), and then stirred for 12 hours at 120 ° C. The reaction solution was concentrated under reduced pressure. Ethyl acetate was added to the residue and extracted with water. The pH of the aqueous layer was adjusted from 3 to 4 with 1 M hydrochloric acid, after which the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and evaporated to thereby yield 4.2 g of the title compound. Appearance: XH RNM coffee powder (DMSO-d6) d 1.19 (3H, t, J = 7.1 Hz), 3.40 (2H, q, J = 7.1 Hz), 3.63 (3H, s), 4.01 (2H, s), 6.17 (1H, d, J = 8.9 Hz), 6.22 (1H, brs), 6.25 (1H, d, J = 2.5 Hz), 6.87-6.90 (2H, m), 7.53 (2H, d, J = 8.6 Hz ), 7.76 (2H, d, J = 8.4 Hz), 8.18 (1H, dd, J = 8.7 Hz, 2.3 Hz), 8.67 (ÍH, d, J = 2.1 Hz), 8.88 (ÍH, brs).

Reference Example 257 Production of ethyl 2-ethyl [2, 5-difluoro-4- (5-nitropyridin-2-yloxy) phenyl] aminoacetate To a solution of ethyl (2, 5-difluoro-4-hydroxyphenyl) aminoacetate (1.1 g , 4.8 ramol) in DMF (25 mL) was added sodium bicarbonate (0.44 g, 5.2 mmol) and methyl iodide (1.69 mL, 28.6 mmol), and the resulting reaction solution was stirred for 2 days at room temperature. Water was added to the reaction mixture, and extracted with ethyl acetate. Once the ethyl acetate layer had been washed with water, the ethyl acetate layer was dried with anhydrous magnesium sulfate, and evaporated. The residue was dissolved in DMF (30 mL), and to this resulting solution were added potassium carbonate (0.72 g, 5.2 mmol) and 2-chloro-5-nitropyridine (0.79 g, 5.0 mmol). The reaction solution was stirred for 2.5 days at room temperature. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and dried over anhydrous magnesium sulfate. The solvent was then evaporated, and the residue was purified by chromatography on silica gel (n-hexane: ethyl acetate = 8: 1), to thereby yield 1.41 g of the title compound. Appearance: Yellow oil XH RNM (CDC13) d 1.27 (3H, t, J = 7.1 Hz), 3.01 (3H, s), 4.05 (2H, s), 4.19 (2H, q, J = 7.1 Hz), 6.77 ( 1H, dd, J = 8.2 Hz, 12.2 Hz), 6.92 (1H, dd, J = 7.2 Hz, 12.8 Hz), 8.49 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.02 (1H, d, J = 2.8 Hz).

The following compounds were produced in the same manner as in Reference Example 257. Table 37 Reference Example 260 Production of 4-. { 3- [3-methyl-4- (5-nitropyridin-2-yloxy) phenyl] -2-oxotetrahydropyrimidin-1-yl} ethyl benzoate Under a nitrogen atmosphere, to a solution of ethyl 4- [3- (4-benzyloxy-3-methyl) phenyl-2-oxotetrahydropyrimidin-1-yl] benzoate (1.82 g, 3.1 mmol) in ethanol- DMF (70 mL- 30 mL) was added 10% palladium-carbon (0.4 g), and the resulting solution was stirred under a hydrogen atmosphere for 4 hours at room temperature. The resulting solution was filtered through Celite, and ethanol was evaporated under reduced pressure to give a DMF solution (30 mL). To this solution was added 2-chloro-5-nitropyridine (0.52 g, 3.3 mmol) and stirred under a nitrogen atmosphere for 14 hours at room temperature, and then for 3 hours at 40 ° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by chromatography on silica gel (n-hexane: ethyl acetate = 10: 1), to thereby produce 1.8 g of the title compound. Appearance: White powder? U RNM (CDC13) d 1.39 (3H, t, J = 7.1 Hz), 2.14 (3H, s), 2.21-2.40 (2H, m), 3.75-3.97 (4H, m), 4.36 ( 2H, q, J = 7.1 Hz), 7.01 (1H, d, J = 9.1 Hz), 7.06 (1H, d, J = 8.6 Hz), 7.23 (1H, dd, J = 2.6 Hz, 8.6 Hz), 7.32 (1H, d, J = 2.6 Hz), 7. 40-7.49 (2H, ra), 7.97-8.07 (2H, m), 8.46 (1H, dd, J = 2.8 Hz, 9.1 Hz), 9.04 (1H, d, J = 2.8 Hz).

Reference Example 261 Production of 3- [4- (5-nitropyridin-2-ylsulfanyl) phenyl] propionic acid To a solution of 2-chloro-5-nitropyridine (1.74 g, 11.0 mmol) and 4-mercaptohydrocinnamic acid (2.00 g , 11.0 mmol) in DMF (30 mL) was added potassium carbonate (4.55 g, 32.9 mmol), and the resulting solution was stirred for 1 hour at 80 ° C. Water and concentrated hydrochloric acid were added to the reaction solution, and then it was cooled with ice. The precipitated solid matter was collected by filtration, to thereby produce 3.29 g of the title compound. Appearance: Pale yellow powder? U RNM (DMSO-d6) d 2.60 (2H, t, J = 7.5 Hz), 2.91 (2H, t, J = 7.5 Hz), 7.07 (1H, d, J = 9.0 Hz), 7.43 (2H, d, J = 8.2 Hz), 7.57 (2H, d, J = 8.2 Hz), 8.39 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.17 (1H, d, J = 2.8 Hz) , 12.19 (1H, s).

Reference Example 262 Production of Ethyl 3- [3-methoxy-4- (5-nitropyridin-2-ylamino) phenyl] propionate To 2-chloro-5-nitropyridine (3.11 g, 20 mmol) was added 3- (4 ethyl-3-methoxyphenyl) propionate (4.38 g, 20 mmol) and acetic acid (10 mL), and the resulting solution was stirred for 13 hours at 100 ° C. To the reaction solution were added ethyl acetate and water. The ethyl acetate layer was separated, washed with brine, a saturated sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 2: 1), thereby producing 3.78 g of the title compound. Appearance: Yellow powder 1H RNM (CDC13) d 1.26 (3H, t, J = 7.1 Hz), 2.61-2.67 (2H, m), 2.93-2.99 (2H, m), 3.89 (3H, s), 4.15 (2H , q, J = 7.1 Hz), 6.73 (1H, d, J = 9.2 Hz), 6.81-6.87 (2H, m), 7.43 (1H, brs), 7.92 (1H, d, J = 8.1 Hz), 8.23 (1H, dd, J = 9.2 Hz, 2.8 Hz), 9.11 (ÍH, d, J = 2.8 Hz).

The following compounds were produced in the same manner as in Reference Example 262.

Table 38 Reference Example 267 Production of: 4- [(5-nitro-2-pyridyl) oxy] benzaldehyde ethylenacetal To a solution of 4- [(5-nitro-2-pyridyl) oxy] benzaldehyde (5.00 g, 20.5 mmol) in benzene (100 μl) were added ethylene glycol (2.28 mL, 41.0 mmol) and p-toluenesulfonic acid (0.50 g), and the resulting solution was heated to reflux for 3 hours while stirring the water with a Dean-Stark. The reaction solution was washed with a solution of saturated sodium bicarbonate, and subsequently washed with brine. The benzene layer was dried over anhydrous magnesium sulfate, and evaporated, thereby yielding 5.88 g of the title compound. Appearance: Yellow powder 2H RNM (CDC13) d 4.00-4.19 (4H, ra), 5.83 (1H, s), 7.00 (1H, d, J = 9.0 Hz), 7.15 (2H, d, J = 8.5 Hz), 7.55 (2H, d, J = 8.5 Hz), 8.45 (1H, dd, J = 9.0 Hz, 2.0 Hz), 9.01 (1H, d, J = 2.0 Hz).

The following compound was produced in the same manner as in Reference Example 267.

Reference Example 268 Acetal ethylene 4- (2-Fluoro-4-nitrophenoxybenzaldehyde H NMR (DMSO-d6) d 3.90-4.10 (4H, m), 5.76 (1H, s), 7.15-7.25 (3H, m), 7.54 (2H, d, J = 8.7 Hz), 8.10 (1H, ddd, J = 1.3 Hz, 2.7 Hz, 9.1 Hz), 8.35 (1H, dd, J = 2.7 Hz, 10.8 Hz).

Reference Example 269 Production of t-butyl [4- (5-nitropyridin-2-yloxy) phenyl] carbamate To a solution of 4- (5-nitropyridin-2-yloxy) phenylamine (2.97 g, 12.85 mmol) in THF di-t-butyl dicarbonate (5.60 g, 25.66 mmol) was added, and the solution The resulting mixture was stirred under reflux for 4 hours. The reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and diethyl ether was added to the resulting product. The white powder obtained was filtered, and the resulting product was washed with diethyl ether, to thereby yield 3.04 g of the title compound. Appearance: Yellow powder XH RNM (CDC13) d 1.53 (9H, s), 6.53 (1H, brs), 7.00 (1H, d, J = 9.2 Hz), 7.09 (2H, d, J = 8.9 Hz), 7.45 ( 2H, d, J = 8.9 Hz), 8.46 (1H, dd, J = 9.2 Hz, 3.0 Hz), 9.03 (1H, d, J = 3.0 Hz ' Reference Example 270 Production of 5- [3-methyl-4- (5-nitropyridin-2-yloxy) benzylidene] thiazolidin-2,4-dione To a solution of 3-methyl-4- (5-nitropyridin-2-) iloxy) benzaldehyde (600 mg, 2.32 mmol) in toluene (35 mL) were added 2,4-thiazolidinedione (270 mg, 2.31 mmol) and piperidine acetate (135 mg, 0.93 mmol). The resulting solution was fixed to a Dean Stark :, and stirred under reflux for 1.5 hours. After being allowed to cool for 17 hours at room temperature, the precipitated yellow powder was filtered, to thereby produce 600 mg of the title compound. Appearance: Yellow powder lU RNM (DMSO-d6) d 2.15 (3H, s), 7.33 (1H, d, J = 8.4 Hz), 7.35 (1H, d, J = 9.1 Hz), 7.52 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.59 (1H, d, J = 2.0 Hz), 7.79 (1H, s), 8.65 (1H, dd, J = 9.1 Hz, 3.0 Hz), 9.02 (1H, d, J = 3.0 Hz), 12.63 (1H, brs).

The following compounds were produced in the same manner as in Reference Example 270.

Table 39 Reference Example 273 Production of N- [4- (2-fluoro-4-nitrophenoxy) phenyl] -N- [2- (4-piperonylpiperazin-1-yl) -2-oxyethyl] acetamide To a solution of N- [ 4- (2-fluoro-4-nitrophenoxy) phenyl] acetamide (0.800 g, 2.76 mmol) in DMF (5 mL) was added 60% sodium hydride (0.118 g, 2.95 mmol). The resulting solution was stirred for 10 minutes at room temperature, after which a solution of l-chloroacetyl-4-piperonylpiperazine (0.870 g, 2.96 mmol) in DMF (4 mL) was added to the reaction solution. The reaction solution was stirred for 2 hours at 60 ° C, and then for 1 hour at 100 ° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (dichloromethane: methanol = 5: 1), to thereby produce 0.730 g of the title compound. Appearance: Yellow oil? U RNM (DMSO-de) d 1.82 (3H, s), 2.20-2. 0 (4H, m), 3.30-3.50 (6H, m), 4.43 (2H, s), 5.98 (2H, s), 6.70-6.85 (3H, m), 7.20-7.30 (3H, m), 7.48 ( 2H, d, J = 8.8 Hz), 8.12 (1H, ddd, J = 1.4 Hz, 2.7 Hz, 10.5 Hz), 8.36 (1H, dd, J = 2.7 Hz, 10.7 Hz).

The following compound was produced in the same manner as in Reference Example 273.

Reference Example 274 3- (4-Benzyloxy-3-phenylphenyl) -1- [2-oxo-2- (4-piperonylpiperazin-1-yl) ethyl] tetrahydropyriraidin-2-one XH NMR (DMSO-d6) d 1.92 -2.08 (2H, m), 2.15 (3H, s), 2.22-2.40 (4H, m), 3.25-3.49 (8H, m), 3.56 (2H, d, J = 5.6 Hz), 4.08 (2H, s) ), 5.09 (2H, s), 5.97 (2H, s), 6.74 (1H, dd J = 1.3 Hz, 7.9 Hz), 6.84 (1H, d, J = 7.9 Hz), 6.85 (1H, d, J = 1.3 Hz), 6.91 (1H, d, J = 8.7 Hz), 6.95 (1H, dd, J = 2.5 Hz, 8.6 Hz), 7.01 (1H, d, J = 2.5 Hz), 7.28-7.34 (HI, m ), 7.36-7. 1 (2H, m), 7.42-7.48 (2H, m).

Reference Example 275 Production of 2-dimethylamino-N- [4- (5-nitropyridin-2-yloxy) phenyl] -N- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] acetamide To one solution of 2-chloro-N- [4- (5-nitropyridin-2-yloxy) phenyl] -N- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] acetamide (0.300 g, 0.528 mmol) in acetonitrile (3 mL) was added at room temperature dimethylamine (0.150 mL, 1.63 mmol), and the resulting solution was stirred for 2 hours at 50 ° C. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (dichloromethane: methanol = 10: 1), with which to produce 0.270 g of the title compound. Appearance: Yellow powder AND RNM (CDCI3) d 2.29 (6H, s), 2. 0-2.45 (4H, m), 3. 02 (2H, s), 3.40-3.46 (4H, m), 3.61 (2H, s), 4.48 (2H, s), 5.95 (2H, s), 6.70-6.77 (2H, m), 6.84 (1H, s), 7.09 (1H, d, J = 9. 0 Hz), 7.19 (2H, d, J = 8.7 Hz), 7.51 (2H, d, J = 8.7 Hz), 8. 51 (1H, dd, J = 2.8 Hz, 9.0 Hz), 9.04 (1H, d, J = 2.8 Hz).

Reference Example 276 Production of methyl 2- [4- (5-nitropyridin-2-yloxy) phenyl] propionate To a solution of 2 - [4 - (5-n-tyrp-idin-2 -i-loxi) -pheni 1 Acetyl or methyl (0.50 g, 1.7 mmol) in DMF (10 mL) were added with 60% sodium hydride (0.153 g, 3.8 mmol) and methyl iodide (0.13 mL, 2.1 mraol), and the solution of The resulting reaction was stirred for 1 hour at 0 ° C. Saturated aqueous ammonium chloride was added to the reaction solution, and it was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated aqueous sodium chloride. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by chromatography on silica gel (n-hexane: ethyl acetate = 8: 1), in order to produce 0.32 g of the composed of the title.

Appearance: Colorless oil? U RNM (CDCI3) d 1.54 (3H, d, J = 7.4 Hz), 3.69 (3H, s), 3.78 (1H, q, J = 7.2 Hz), 7.03 (1H, d, J = 9.1 Hz), 7.09-7.15 (2H, m), 7.36-7.41 (2H, m), 8.48 (1H, dd, J = 9.1, 2.8 Hz), 9.05 (ÍH, d, J = 2.8 Hz).

Reference Example 277 Production of 3-. { 3-Ratoxy-4- [methyl (5-nitropyridin-2-yl) araino] phenyl} Ethyl propionate To a solution of ethyl 3 - [3-methoxy-4- (5-nitro-rumin-2-ylamino) ethyl] propionate (3.70 g, 11 mmol) in DMF (60 mL) were added Sodium hydride under ice cooling (60%, 490 mg, 12 mmol) and methyl iodide (0.77 mL, 12 mmol) and the resulting reaction solution was stirred for 2 hours gradually warming to room temperature. The reaction solution was concentrated under reduced pressure. Ethyl acetate was added to the residue, washed with water and brine, and then dried with anhydrous magnesium sulfate. The solvent was evaporated, thereby producing 4.27 g of the title compound. Appearance: Yellow oil substance XH RNM (CDCI3) d 1.27 (3H, t, J = 7.1 Hz), 2.66-2.7K2H, m), 2.98-3.04 (2H, m), 3.46 (3H, s), 3. 78 (3H, s), 4.17 (2H, q, J = 7.1 Hz), 6.12 (1H, brd, J = 9.5 Hz), 6.87-6.90 (2H, m), 7.11-7.14 (ÍH, m), 7.97 -8.02 (ÍH, m), 9.11 (ÍH, d, J = 2.7 Hz).

The following compounds were produced in the same manner as in Reference Example 277.

Table 40 94 Table 41 Table 42 Reference Example 291 Production of N- [4- (5-nitropyridin-2-yloxy) f enyl] -2- (-piper oni Ipipera zin-1-yl) acetamide A solution of acid (4-piperoni Ipipera z in 1-yl) acetic acid (13.9 g, 50 mmol) was suspended in DMF (400 mL), and monohydrate 1-hydroxybenzot zol (8.42 g, 55 mmol) was added to the resulting suspension, hydrochloride l-ethyl-3- (3-dime ti larainopr opi 1) ca rbodi imide (10.5 g, 55 mmol) and 4- (5-ni t ropi r idin-2-i loxi) feni lamina (11.6 g, 50 mmol) under cooling with ice. The resulting solution was stirred for 6 hours at room temperature. The reaction solution was concentrated under reduced pressure. Ethyl acetate was added to the residue, and it was washed with a saturated sodium bicarbonate solution and brine. The organic layer was allowed to stand overnight at room temperature, and the resulting precipitated crystals were collected by suction filtration, to thereby produce 12.8 g of the title compound. Appearance: White powder XH NMR (CDC13) d 2.53 (4H, brs), 2.64 - 2.65 (H, m), 3.15 (2H, s), 3.46 (2H, s), 5.95 (2H, s), 6.76 (2H , brs), 6.86 (1H, s), 7.04 (1H, d, J = 9.1 Hz), 7.14 (2H, d, J = 8.7 Hz), 7.67 (2H, d, J = 8.9 Hz), 8.47 (1H , dd, J = 9.1 Hz, 2.8 Hz), 9.03 (1H, d, J = 2.8 Hz), 9.24 (1H, brs).

Reference Example 292 Production of. { met anosul f oni 1 [3 -me t oxy- 4 - (5-ni t r opi r idin-2 -i loxi) feni 1] araino} ace t a t o of ethyl A solution of [3-methyloxy- (5-ni t ropir idin-2 -i loxi) phenylamino] ace tat or ethyl (2.43 g, 7.00 mmol) was dissolved in THF (15 mL), dichloromethane (20 mL) and DMF (10 mL), and to the resulting solution were added triethylamine (1.95 mL, 13.99 mmol), 4-dimethylaminopyridine (0.86 g, 7.00 mmol). mmol) and methanesulfonyl chloride (1.08 mL, 13.99 mmol) under cooling with ice. The resulting solution was stirred for 14 hours at 30 ° C. Water was added to the reaction mixture, and extracted with dichloromethane. The dichloromethane layer was washed with water and brine. The dichloromethane layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 2), thereby producing 1.10 g of the composed of the title. Appearance: Yellow oil ÍH RNM (CDC13) d 1.32 (3H, t, J = 7.3 Hz), 3.18 (3H, s), 3.75 (3H, s), 4.26 (2H, q, J = 7.3 Hz), 4.49 ( 2H, s), 7.09 (1H, d, J = 9.1 Hz), 7.15 (2H, d, J = 1.2 Hz), 7.25 (1H, s), 8.48 (1H, dd, J = 9.1 Hz, 2.8 Hz) , 8.98 (1 H, d, J = 2.8 Hz). The following compounds were produced in the same manner as in Reference Example 292.

Table 43 Reference Example 296 Production of 3- [4- (5-nitropyridin-2-yloxy) phenyl] -n-propanol To a solution of 3- [4- (5-nitropyridin-2-yloxy) phenyl] propionic acid (2.64 g, 9.2 mmol) in THF (50 mL) was added dropwise a THF solution of 1 M borane-THF complex (38.4 mL, 38.4 mmol) under ice-cooling. The reaction solution was stirred for 2 hours at room temperature. Water was added to the reaction mixture, and extracted with ethyl acetate, and the ethyl acetate layer was washed with water and then brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, after which the solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 1), with which to produce 1.17 g of the title compound. Appearance: Green oil and RNM (CDC13) d 1.90-1.96 (2H, m), 2.73-2.79 (2H, m), 3.69-3.74 (2H, m), 7.00-7.09 (3H, m), 7.26-7.30 ( 2H, m), 8.44-8.49 (1H, m), 9.05 (1H, d, J = 2.6 Hz).

Reference Example 297 Production of 2-. { 4 - [3- (t-Butyldimethylsilanyloxy) -propyl] phenoxy} -5-nitropyridine To a solution of 3- [4- (5-nitropyridin-2-yloxy) phenyl] -n-propanol (1.17 g, 4. 3 ramol) in DMF (10 mL) were added imidazole (580 mg, 8.5 ramol) and t-butylchlorodimethylsilane (640 mg, 4.2 mmol), and the resulting solution was stirred for 13 hours at room temperature. Water was added to the reaction mixture, and extracted with diethyl ether, and the diethyl ether layer was washed with water and then brine. The The diethyl ether layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 5: 1), thereby producing 1.14 g of the composed of the title. Appearance: Pale yellow powder Vi RNM (CDC13) d 0.07 (6H, s), 0.92 (9H, s), 1.84-1.89 (2H, m), 2.69-2.75 (2H, m), 3.66 (2H, t, J = 6.3 Hz), 6.99-7.08 (3H, m), 7.27 (2H, d, J = 7.6 Hz), 8.46 (1H, dd, J = 8.9 Hz, 3.0 Hz), 9.05 (HI, d, J = 3.0 Hz).

The following compound was produced in the same manner as in Reference Example 297.

Reference Example 298 2-. { 4- [2- (t-Butyldimethylsilanyloxy) ethyl] phenoxy} -5-Nitropyridine XH NMR (CDCl 3) d 0.00 (6H, s), 0.88 (9H, s), 2.86 (2H, t, J = 6.9 Hz), 3.84 (2H, t, J = 6.9 Hz), 7.00 ( 1H, d, J = 9.2 Hz), 7.05-7.08 (2H, m), 7.26-7.31 (2H, m), 8.46 (1H, dd, J = 9.2 Hz, 3.0 Hz), 9.05 (1H, d, J = 3.0 Hz).

Reference Example 299 Production of Ethyl 4- [4- (5-nitropyridin-2-yloxy) phenyl] butanoate To a solution of 4- [4- (5-nitropyridin-2-yloxy) phenyl] butanoic acid (9.98 g , 33.01 mmol) in dichloromethane was added ethanol (5.59 mL, 99.01 mmol), 4-dimethylaminopyridine (400 rag, 3.27 mmol), triethylamine (13.81 mL, 99.08 mmol) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (7.6 g, 39.65 ramol) under cooling with ice, and the resulting solution was stirred for 20 minutes under ice-cooling and then for 1 hour at room temperature. The reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate, and the ethyl acetate layer was washed with 1 N hydrochloric acid, a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 5: 1), to produce 6.77. g of the title compound. Appearance: Colorless oil Y RNM (CDC13) d 1.27 (3H, t, J = 7.0 Hz), 1.99 (2H, dt, J = 15.0 Hz, 7.5 Hz), 2.36 (2H, t, J = 7.5 Hz), 2.70 (2H, t, J = 7.5 Hz), 4.14 (2H, q, J = 7.0 Hz), 7.01 (1H, d, J = 9.0 Hz), 7.08 (2H, d, J = 8.5 Hz), 7.26 (2H , d, J = 8.5 Hz), 8.46 (1H, dd, J = 9.0 Hz, 3.0 Hz), 9.04 (1H, d, J = 3.0 Hz).

Reference Example 300 Production of methyl 3- [4- (5-nitropyridin-2-ylsulfanyl) phenyl] propionate To a solution of 3- [4- (5-nitropyridin-2-ylsulfanyl) phenyl] propionic acid (86.0 g , 0.283 mmol) in DMF (1 mL) potassium carbonate (59.0 mg, 0.424 mmol) and methyl iodide (0.0260 mL, 0.424 mmol) were added, and the resulting solution was stirred for 1 hour at room temperature. Water was added to the reaction mixture, and then cooled with ice. The precipitated solid matter was collected by filtration, to thereby yield 76.9 mg of the title compound. Appearance: Light brown powder? U RNM (DMSO-de) d 2.70 (2H, t, J = 7.6 Hz), 2.94 (2H, t, J = 7.6 Hz), 3.60 (3H, s), 7.07 (1H, d) , J = 8.9 Hz), 7.43 (2H, d, J = 8.1 Hz), 7.57 (2H, d, J = 8.1 Hz), 8.39 (1H, dd, J = 2.7 Hz, 8.9 Hz), 9.17 (1H, d, J = 2.7 Hz).

Reference Example 301 Production of ethyl (Z) -3- [A - (5-nitro-2-pyridyloxy) phenyl] -2-butenoate To a suspension of 60% sodium hydride (1.28 g, 32.0 mmol) in THF (80 mL) was added dropwise a solution of triethyl phosphonoacetate (8.71 g, 38.8 mmol) in THF (40 mL) under ice-cooling, and the resulting solution was stirred for 10 minutes at the same temperature. To the reaction solution was added 4- [(5-nitro-2-pyridyl) oxy] acetophenone (5.90 g, 22.8 mmol) and the resulting solution was stirred at the same temperature for 10 minutes, and then stirred at room temperature for 60 hours. TO Saturated ammonium chloride was added to the reaction solution and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution, and then washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 5: 1), to produce 1.17. g of the title compound. Appearance: Colorless needles? U RNM (CDC13) d 1.13 (3H, t, J = 7.1 Hz), 2.20 (3H, d, J = 1.4 Hz), 4.02 (2H, q, J = 7.1 Hz), 5.93 (1H , q, J = 1.4 Hz), 7.02 (1H, d, J = 9.0 Hz), 7.12 (2H, d, J = 8.6 Hz), 7.29 (2H, d, J = 8.6 Hz), 8.45 (1H, dd , J = 9.0 Hz, 2.8 Hz), 9.03 (ÍH, d, J = 2.8 Hz). The following compounds were produced in the same manner as in Reference Example 301.

Reference Example 302 | E) -3-. { 4- [4- (3, 4-dichlorobenzoylamino) -2-fluoro phenoxy] phenyl} Ethyl acrylate Melting point: 166-167 ° C Table 44 Reference Example 306 Production of ethyl 3- [4- (5-nitropyridine-2-carbonyl) phenyl] propionate A solution of bi s (tributyl t-year) (1.37 g, 2.36 mmol) in toluene (7 mL ) was added under an argon atmosphere to 2-chloro-5-nitroglyphine (0.325 g, 2.05 mmol), bi s (dibenz 1 idenacet ona) pa ladium (0) (18.1 mg, 0.0315 mraol), tri (2-fur i 1) fos f ina (29.3 mg, 0.126 mmol) and 4A molecular sieves (1.90 g), and the resulting solution was heated to reflux for 1 hour. To the reaction solution was added bis (dibenzylideneacetone) palladium (0) (27.2 mg, 0.0472 mmol) and t ri (2-furyl) phosphine (43.9 mg, 0.189 mmol), and subsequently a solution of 4- [2-ethoxycarbonyl] ethyl chloride was added. ] benzoyl (0.379 g, 1.57 rare) in toluene (5 mL). The resulting reaction solution was stirred for 4 hours at 80 ° C. Saturated aqueous potassium fluoride was added to the reaction solution and stirred for 0.5 hour at room temperature. The insoluble matter was then filtered. The filtrate was extracted with ethyl acetate, and the ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by chromatography on colurane on silica gel (n-hexane -> n-hexane: ethyl acetate = 4: 1), to thereby produce 0.323 g of the title compound. Appearance: Pale yellow powder l U RNM (CDC13) d 1.22 (3H, t, J = 7.1 Hz), 2.65 (2H, t, J = 7.7 Hz), 3.03 (2H, t, J = 7.7 Hz), 4.12 ( 2H, q, J = 7.1 Hz), 7.34 (2H, d, J = 8.3 Hz), 8.00 (2H, d, J = 8.3 Hz), 8.18 (1H, d, J = 8.5 Hz), 8.65 (1H, dd, J = 8.5 Hz, 2.6 Hz), 9.49 (1H, d, J = 2.6 Hz).

Reference Example 307 Production of Ethyl 3- [4- (4-araphenophenoxy) phenyl] propionate To a suspension of 5% palladium-carbon (0.50 g) in ethanol (50 mL) was added 3- [4- (4 ethyl nitrophenoxy) phenyl] propionate (5.00 g, 15.9 mmol), and the resulting solution was subjected to catalytic reduction at atmospheric pressure and at room temperature. Once the absorption of the hydrogen was stopped, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, to thereby yield 4.52 g of the title compound. Appearance: Light brown oil U RNM (CDC13) d 1.22 (3H, t, J = 7.1 Hz), 2.57 (2H, t, J = 7.8 Hz), 2.88 (2H, t, J = 7.8 Hz), 3.55 (2H, brs), 4.10 (2H, q, J = 7.1 Hz), 6.64 (2H, d, J = 8.8 Hz), 6.78-6.86 (4H, m), 7.08 (2H, d, J = 8.6 Hz) .

The following compounds were produced in the same manner as in Reference Example 307.

Table 45 15 20 Table 46 Table 47 Table 48 Table 49 -CO- means a group of j. Henceforth in the present -CO- indicates the same meaning).

Table 50 Table 51 Table 52 Table 53 Table 54 fifteen twenty Table 55 Table 56 Table 57 Reference Example 404 Production of methyl 3- [(4-hydroxyphenyl) methylamino] -propionate Methyl 3- [(4-benzyloxyphenyl) methylamino] -propionate (27.3 g, 91.1 mmol) was dissolved in ethanol (300 mL), and the resulting solution was cooled with ice and 10% palladium-carbon (3.0 g) was added. The resulting solution was stirred for 4.5 hours at room temperature under a hydrogen atmosphere. The reaction solution was filtered through Celite to remove insoluble matter, and the filtrate was concentrated under reduced pressure to thereby produce 19.1 g of the title compound. Appearance: Red oil? U RNM (CDC13) d 2.51-2.56 (2H, m), 2.83 (3H, brs), 3.57 (2H, brs), 3.66 (3H, s), 4.99 (1H, brs), 6.71- 6.74 (4H, m).

The following compounds were produced in the same manner as in Reference Example 404.

Reference Example 405 [Acetyl (4-hydroxyphenyl) amino] ethyl acetate and NMR (CDC13) d 1.26 (3H, t, J = 7.1 Hz), 1.92 (3H, s), 4.19 (2H, q, J = 7.1 Hz), 4.34 (2H, s), 6.16 (1H, s), 7 (2H, d, J = H Z: 7.21 (2H, d, J = 8.8 Hz) Table 58 Reference Example 411 Production of [4- (5-aminopyridin-2-yloxy) f-enyl] (4-piperonylpiperazin-1-yl) methanone [4- (5-Nitropyridin-2-yloxy) phenyl] (4-piperonyl piperazine -1-yl) methanone (0.36 g, 0.78 mmol) was dissolved in a mixed solvent consisting of ethanol (5 raL) and THF (5 raL). To the resulting solution was added 5% platinum-carbon (0.06 g), and stirred at room temperature under a hydrogen atmosphere. Two hours later, the 5% platinum-carbon was removed by filtration, and the solvent was evaporated under reduced pressure, thereby producing 0.32 g of the title compound. Appearance: Pale yellow amorphous powder? U RNM (CDC13) d 2.43 (4H, brs), 3.44 (2H, s), 3.58 (6H, brs), 5.95 (2H, s), 6.74 (2H, s), 6.80 ( 1H, d, J = 8.6 Hz), 6.85 (1H, s), 7.05 (2H, d, J = 8.6 Hz), 7.10 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.40 (2H, d, J = 8.7 Hz), 7.74 (1H, d, J = 2.6 Hz).

The following compounds were produced in the same manner as in Reference Example 411.

Reference Example 412 4- [5- (4-Trif luoromethyl-phenoxymethyl) pyridin-2-yloxy] phenylamine AND NMR (CDCI3) d 3.63 (2H, brs), 5.02 (2H, s), 6.70 (2H, d, J = 8.9 Hz), 6.88 (1H, d, J = 8.4 Hz), 6.94 (2H, d, J = 8.9 Hz), 7.01 (2H, d, J = 8.6 Hz), 7.55 (2H, d, J = 8.4 Hz), 7.72 (1H, dd, J = 8.4 Hz, 2.5 Hz), 8.22 (1H, d, J = 2.3 Hz).

Reference Example 413 3-Methyl-4- [5- (4-trifluororaethylphenoxymethyl) pyridin-2-yloxy] phenylamine AND NMR (CDC13) d 2.08 (3H, s), 3.58 (2H, brs), 5.02 (2H, s ), 6.65 (1H, dd, J = 8.2 Hz, 2.8 Hz), 6.60 (1H, d, J = 2.8 Hz), 6. 83-6.87 (2H, m), 7.02 (2H, d, J = 8.9 Hz), 7.56 (2H, d, J = 9.1 Hz), 7.72 (1H, dd, J = 8.6 Hz, 2.5 Hz), 8.21 ( 1H, d, J = 2.5 Hz).

Reference Example 414 2-. { [4- (-Aminophenoxy) phenyl] methylamino} -1- (4-piperonylpiperazin-1-yl) ethanone and RNM (CDCI3) d 2.41 (4H, t, J = 5.1 Hz), 2.99 (3H, s), 3.42 (2H, s), 3.48 (2H, t , J = 4.8 Hz), 3.50 (2H, brs), 3.62 (2H, t, J = 4.8 Hz), 4.04 (2H, s), 5.95 (2H, s), 6.61-6.68 (4H, m), 6.73 -6.88 (7H, m).

Reference Example 415 2-. { [3- (5-Aminopyridin-2-yloxy) phenyl] -ethylaraine} -1- (4-pipe oniIpiperazin-1-yl) ethanone? U RNM (CDCI3) d 2.40 (4H, t, J = 4.9 Hz), 3.00 (3H, s), 3.41 (2H, s), 3.44-3 . 6 (2H, m), 3.51 (2H, brs), 3.59- 3. 61 (2H, m), 4.06 (2H, s), 5.95 (2H, s), 6.35-6. 5 (3H, m), 6.70-6.74 (3H, m), 6.85 (1H, s), 7.05 (1H, dd, J = 8.6 Hz, 3.1 Hz), 7.12-7.18 (HI, m), 7.73 (1H , d, J = 3.1 Hz). The following compounds were prepared in the same manner as in Reference Example 415.

Table 59 Table 60 Table 61 Table 62 Table 63 H2N Table 64 Table 65 Table 66 (E means the number of methylene groups, henceforth in the present E it indicates the same meaning).

Table 67 Table 68 Table 69 Table 70 Reference Example 488 Production of Ethyl [4- (4-amino-2-fluorophenoxy) phenylsulfanyl] acetate To a solution of ethyl [4- (2-fluoro-4-nitrophenoxy) phenylsulfanyl] acetate (4.93 g, 14.0 mmol ) in ethanol (100 mL) was added tin chloride dihydrate (9.50 g, 42.1 mmol), and the resulting solution was stirred for 8 hours at 50 ° C. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with 1 M hydrochloric acid, a saturated sodium bicarbonate solution, and brine, dried over anhydrous sodium sulfate, and evaporated, thereby yielding 3.45 g of the title compound. Appearance: Coffee oil lU NMR (CDC13) d 1.20 (3H, t, J = 7.1 Hz), 3.53 (2H, s), 3.80-4.20 (4H, m), 6.37-6. 5 (ÍH, m), 6.49 (1H, dd, J = 2.6 Hz, 12.0 Hz), 6.80-7.00 (3H, m), 7.38 (2H, d, J = 8.9 Hz). The following compounds were produced in the same manner as in Reference Example 488.

Reference Example 489 2-. { Allyl [4- (5-aminopyridin-2-yloxy) -3-fluoro-phenyl] amino} -1- (-piperonylpiperazin-1-yl) ethanone? U RNM (CDCI3) d 2.44-2.46 (4H, m), 3.44 (4H, brs), 3.44 (2H, s), 3.83 (2H, brs), 3.98 (2H, d, J = 4.8 Hz), 4.03 (2H, s), 5.16-5.30 (2H, m), 5.82-5.95 (HI, m), 5.95 (2H, s), 6.35-6.46 (2H, m), 6.71-6.74 (3H, m), 6.85-6.87 ( ÍH, m), 6.96-7.07 (2H, m), 7.63-7.64 (ÍH, m).

Reference Example 490 (E) -3- [3- (5-Aminopyridin-2-yloxy) phenyl] -1- (4-piperonylpiperazin-1-yl) propenone MS 458 (M +).

Reference Example 491 Production of methyl 3- [4- (5-aminopyridin-2-ylsulphanyl) phenyl] propionate To a solution of methyl 3- [4- (5-nitropyridin-2-ylsulphanyl) phenyl] propionate (2.97 g, 9.33 mmol) in methanol (50 mL) were added sodium borohydride (0.590 g, 15.6 mmol) and 10% palladium-carbon (1.80 g), and the resulting solution was stirred for 24 hours at room temperature under one atmosphere of hydrogen at atmospheric pressure. The reaction solution was filtered through Celite, and concentrated hydrochloric acid (1.5 mL) was added to the resulting filtrate, and concentrated under reduced pressure. A solution of saturated sodium bicarbonate was added to the residue, and it was extracted with ethyl acetate, and the ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby produce 2.49 g of the title compound. Appearance: Yellow powder? RNM (CDCI3) d 2.62 (2H, t, J = 7.6 Hz), 2.93 (2H, t, J = 7.6 Hz), 3.67 (3H, s), 6.87 (1H, dd, J = 2.9 Hz, 8.4 Hz) , 6.98 (1H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.2 Hz), 7.35 (2H, d, J = 8.2 Hz), 8.01 (1H, d, J = 2.9 Hz).

Reference Example 492 Production of Ethyl 3- [4- (5-aminopyridin-2-yloxy) phenyl] acrylate To a solution of ethyl 3- [4- (5-nitropyridin-2-yloxy) phenyl] acrylate (2.02 g, 6.43 mmol) in methanol (100 mL) were added zinc (6.3 g, 96.3 mmol) and ammonium chloride (710 mg, 13.27 mmol). The resulting reaction solution was stirred for 2.5 hours under reflux, then acetic acid (5 mL) was added, and stirred for 20 minutes under reflux. The insoluble matter was filtered through Celite, after which the filtrate was concentrated under reduced pressure. To the residue was added 5% potassium hydrogen sulfate (150 mL), the mixture was extracted with dichloromethane, and the dichloromethane layer was washed with a saturated sodium bicarbonate solution and brine. The dichloromethane layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby yield 1.78 g of the title compound.

Appearance: Yellow oil XH RNM (CDCI3) d 1.34 (3H, t, J = 7.1 Hz), 3.58 (2H, brs), 4.26 (2H, q, J = 7.1 Hz), 6.35 (1H, dd, J = 16.0 Hz, 2.0 Hz), 6.81 (1H, d, J = 8.6 Hz), 7.05 (2H, d, J = 8.6 Hz), 7.10 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.50 (2H, d, J = 8.6 Hz), 7. 66 (1H, dd, J = 16.0 Hz, 3.0 Hz), 7.73 (1H, d, J = 3.0 Hz).

Reference Example 493 Production of 3- (4- (5-amino-4-methylpyridin-2-yloxy) phenyl) -1- (4-piperonylpiperazin-1-yl) propan-l-one 3- (4-hydroxyphenyl) -1- (4-piperonylpiperazin-li 1) propan-1 -one (0.38 g, 1.0 mmol) was dissolved in DMF (6 mL). To the resulting solution was added 60% sodium hydride (0.05 g, 1.2 mmol) and 2-chloro-4-methyl-1 -5-nitropyridine (0.196 g, 1.1 mmol), and the reaction solution The resulting mixture was stirred overnight at room temperature. Saturated aqueous ammonium chloride was added to the reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (ethyl acetate), to thereby produce intermediate 3- (4- ( 4-methyl-5-nitropyridin-2-yloxy) phenyl) -1- (4- piperoni Ipipera zin-1-i 1) propan-1 -one. The 3- (4- (4-methyl-5-nitropyridin-2-yloxy) phenyl) -1- (4-piperoni Ipiper az in- 1-i 1) propan-1 -one was dissolved in a mixed solvent consisting of of ethanol (4 mL) and dioxane (1 mL). To this solution was added 10% palladium-carbon (0.034 g), and the resulting solution was subjected to catalytic reduction for 8 hours at atmospheric pressure and room temperature. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, and the residue was purified by chromatography on silica gel (dichloromethane: methanol = 20: 1), to thereby produce 0.22 g of the title co-tax. Appearance: Lightly yellow oil XH NMR (CDC13) d 2.18 (3H, s), 2.30 -2.45 (4 H, m), 2.56-2.63 (2H, m), 2.91 -2.97 (2H, m), 3.30 - 3.50 ( 6H, m), 3.55-3.70 (2H, m), 5.95 (2H, s), 6.65-6.80 (3H, m), 6.84 (1H, s), 6.95-7.05 (2H, m), 7.15 - 7.20 ( 2H, m), 7.64 (ÍH, s).

Reference Example 494 Production of 3-. { 4- [4- (3, -dichlorobenzoylamino) -phenoxy] phenyl} ethyl propionate A solution of 3,4-dichlorobenzoyl chloride (3.65 g, 17.4 mmol) was added dropwise under cooling with The ice was added to a solution of ethyl 3- [4- (4-aminophenoxy) phenyl] propionate (4.52 g, 15.9 mmol) and triethylamine (2.65 mL, 19.0 mmol) in THF (80 mL), and the resulting solution was stirred for 1 hour at the same temperature. Water was added to the reaction mixture, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate and evaporated. The residue was recrystallized from ethanol containing water to yield 6.67 g of the title compound. Appearance: Colorless needles Melting point: 139-141 ° C The following compounds were produced in the same manner as in Reference Example 494.

Reference Example 495 Ethyl 3- [4- (5-phenoxycarbonylaminopyridin-2-yloxy) phenyl] propionate MS 406 (M +).

Table 71 Table 72 Table 73 Table 74 Table 75 Table 76 3. 91 (3H, s), 6.99- 7.04 (HH, m), 7.32-7.37 (HH, m), 7.45-7.50 (1H, m), 7.74- 539 -H -H COOCH3 7.80 (3H, m), 7.86 - 7.90 (1H, m), 7.96- 8.01 (3H, m), 8.22- 8.27 (2H, m).

Table 77 Table 78 Table 79 Table 80 Reference Example 580 Production of 3-. { 4- [5- (3,4-dichlorobenzoylamino) -pyridin-2-yloxy] -3-methoxyphenyl} Ethyl propionate Under ice cooling, to a solution of ethyl 3- (4- (5-aminopyridin-2-yloxy) -3-methoxyphenyl) propionate (1.43 g, 4.5 mmol) in dichloromethane (30 mL) was added pyridine (0.44 mL, 5.4 mmol) , and then 3,4-dichlorobenzoyl chloride (0.99 g, 4.7 mmol). The resulting solution was stirred for 1 hour under cooling with ice, and then for 10 hours at room temperature. To the resulting reaction solution was added 10% hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was washed with water, dried over anhydrous magnesium sulfate and evaporated. Diethyl ether was added to the residue, and stirred. The precipitates were collected by filtration. After washing with water and diethyl ether, the precipitates were dried with air at 60 ° C, thereby producing 0.52 g of the title compound. Appearance: White powder ln RNM (CDCI3) d 1.26 (3H, t, J = 7.1 Hz), 2.56- 2. 79 (2H, m), 2.91-3.09 (2H, m), 3.75 (3H, s), 4.15 (2H, q, J = 7. 1 Hz), 6.75 (3H,), 7.10 (1H, d, J = 8.0 Hz), 7.56 (1H, d, J = 8. 2 Hz), 7.99 (1H, d, J = 8.1 Hz), 8.17 (1H, s), 8.69 (1H, d, J = 9.2 Hz), 8.79 (1H, s), 9.52 (1H, brs).

The following compounds were produced in the same manner as in Reference Example 580.

Table 81 Table 82 Reference Example 589 Production of Ethyl 4- [5- (3, 4-dimethylbenzoylamino) -pyridin-2-yloxy] benzoate To a solution of ethyl 4- (5-aminopyridin-2-yloxy) benzoate (14.15 g, 54.8 mmol) in DMF (100 mL) were added 3, -dimethylbenzoic acid (8.23 g, 54.8 mmol), 1-hydroxybenzotriazole monohydrate (8.4 g, 54.8 mmol), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride ( 12.6 g, 65.7 mmol) under cooling with ice, and then stirred for 30 minutes under ice-cooling and for 17 hours at room temperature. The reaction solution was concentrated under reduced pressure. Water (200 mL) was added to the residue, and extracted with ethyl acetate (250 mL). The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 2: 1), thereby producing 16.15 g of the title compound. Appearance: White powder RNM (CDC13) d 1.39 (3H, t, J = 7.1 Hz), 2.33 (6H, s), 4.37 (2H, q, J = 7.1 Hz), 6.99 (1H, d, J = 9.7 Hz ), 7.15 (2H, d, J = 8.7 Hz), 7.24 (1H, d, J = 7.7 Hz), 7.59 (1H, dd, J = 7.7 Hz, 2.0 Hz), 7.65 (1H, d, J = 2.0 Hz), 7.90 (1H, brs), 8.07 (2H, d, J = 8.7 Hz), 8.25-8.35 (2H, m).

The following compounds were produced in the same manner as in Reference Example 589.

Table 83 Reference Example 592 Production of 3-. { - [5- (3,4-dichlorobenzoylamino) -pyridin-2-yloxy] -3-ethoxyphenyl} ethyl propionate To a solution of ethyl 3- [3-ethoxy-4- (5-nitropyridin-2-yloxy) phenyl] propionate (0.82 g, 2.3 mmol) in ethanol (40 mL) was added 10-palladium-carbon. % (0.15 g) under a nitrogen atmosphere, and the resulting solution was stirred under an atmosphere of hydrogen at atmospheric pressure for 1 hour at room temperature. The palladium-carbon was removed by filtration, and the filtrate was concentrated. The filtrate obtained (0.58 g) was dissolved in dichloromethane (30 mL), and to the resulting solution were added pyridine (0.17 mL, 2.1 mmol) and 3,4-dichlorobenzoyl chloride (0.39 g, 1.84 mmol) under cooling with ice. The resulting solution was stirred under ice-cooling for 1 hour, and then stirred for 12 hours at room temperature. The reaction solution was made acidic by adding 10% hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was washed with a saturated sodium bicarbonate solution, dried over magnesium sulfate anhydrous, and evaporated, in order to produce 0.94 g of the title compound. Appearance: Yellow amorphous powder RNM (CDCI3) d 1.18 (3H, t, J = 7.0 Hz), 1.26 (3H, t, J = 7.1 Hz), 2.53-2.71 (2H, m), 2.86-3.01 (2H, m ), 3.98 (2H, q, J = 7.0 Hz), 4.15 (2H, q, J = 7.1 Hz), 6.78-6.88 (2H, m), 6.95 (1H, d, J = 8.8 Hz), 7.06 (1H , d, J = 7.9 Hz), 7.58 (1H, d, J = 8.3 Hz), 7.65-7.77 (2H, m), 7.98 (1H, d, J = 2.1 Hz), 8.14 (1H, dd, J = 8.8 Hz, 2.7 Hz), 8.19 (1H, d, J = 2.3 Hz).

The following compound was produced in the same manner as in Reference Example 592.

Reference Example 593 N-. { 6- [4- (3-hydroxypropyl) phenoxy] pyridin-3-yl} -4-trifluoromethylbenzamide? U RNM (CDCI3) d 1.86-1.97 (2H, m), 2.70-2.75 (2H, m), 3. 68-3.73 (2H, m), 6.95 (1H, d, J = 8.7 Hz), 7.03-7.08 (2H, m), 7. 23 (2H, d, J = 8.4 Hz), 7.77 (2H, d, J = 8.2 Hz), 7.84 (1H, brs), 7.99 (2H, d, J = 8.2 Hz), 8.20-8.23 (ÍH, m ), 8.26 (1H, d, J = 2.6 Hz).

Reference Example 594 Production of 2- (4-. {5- [3- (3, 4-dichlorophenyl) -ureido] pyridin-2-yloxy] phenyl) ethyl acetate To a solution of 2- [4 - methyl (5-aminopyridin-2-yloxy) phenyl] acetate (0.44 g, 1.7 mmol) in dichloromethane (7 raL) was added 3,4-dichlorophenylisocyanate (0.353 g, 1.9 ramol), and the resulting reaction solution was stirred for 1 hour at room temperature. Diisopropyl ether was added to the reaction solution. The insoluble matter was removed by filtration, in order to produce 0.60 g of the title compound. Appearance: White powder XH NMR (DMSO-de) d 3.63 (3H, s), 3.69 (2H, s), 6.99-7.05 (3H, m), 7.26-7.30 (2H, m), 7.35 (1H, dd, J = 8.8, 2.4 Hz), 7.52 (1H, d, J = 8.8 Hz), 7.86 (1H, d, J = 2.4 Hz), 7.98 (1H, dd, J = 8.8, 2.8 Hz), 8.18 (1H, d, J = 2.7 Hz), 8.91 (1H, s), 9.10 (H, s). The following compounds were produced in the same manner as in Reference Example 594.

Table 84 Table 85 Table 86 Table 87 Reference Example 606 Production of 3- (4-. {5- (3- (4-trifluororaethyl-phenyl) ureido] pyridin-2-yloxy} phenyl) propionate of raethyl 3- [4- (5-nitropyridine Methyl-2-yloxy) phenyl] propionate (1.00 g, 3.3 ramol) was dissolved in a mixed solvent consisting of THF (1 mL) and ethanol (120 mL). To the resulting solution was added 10% palladium-carbon (100 mg), and stirred for 23 hours at room temperature under a hydrogen atmosphere. The reaction solution was filtered and the filtrate was concentrated. To the residue was added THF (20 mL), triethylamine (0.917 mL, 6.6 mmol) and phenyl 4-trifluoromethyl isocyanate (0.61 mL, 4.3 mmol), and the resulting solution was stirred for 20 hours at room temperature. The reaction solution was evaporated under reduced pressure. The residue was washed with ethyl acetate, to thereby yield 850 mg of the title compound. Appearance: XU RNM white powder (DMSO-d6) 6 2.62-2.68 (2H, m), 2.83-2.88 (2H, m), 3.60 (3H, s), 6.97-7.02 (3H, m), 7.24 (2H, d, J = 8.4 Hz), 7.65-7.69 (4H, ra), 7.99 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.19 (1H, d, J = 2.8 Hz), 8.88 (1H, s) 9.20 (1H, s).

Reference Example 607 Production of 3-fluoro-4-. { 5- [(4-trifluoromethyl-benzylidene) araino] pyridin-2-yloxy} methyl ratsyl 4- (5-Aminopyridin-2-yloxy) -3-fluorobenzoate (2.0 g, 7.63 mraol) was dissolved in methanol (50 mL). To the resulting solution was added 4-trifluoromethylbenzaldehyde (1.04 mL, 7.63 mmol), and refluxed for 6 hours. The reaction solution was cooled to room temperature, and the resulting precipitated crystals were collected by suction filtration. The collected crystals were washed with methanol, thereby producing 2.81 g of the title compound. Appearance: Pale gray powder? U RNM (DMSO-d6) d 3.89 (3H, s), 7.32 (1H, d, J = 8.7 Hz), 7.48-7.54 (1H, m), 7.85-7.92 (4H, m) , 8.01 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.13-8.16 (3H, m), 8.86 (1H, s). The following compounds were produced in the same manner as in Reference Example 607.

Table 88 Reference Example 612 Production of 4-. { 5- [1- (4-trifluoromethylphenyl) -ethylidenaraino] pyridin-2-yloxy} Ethyl benzoate ethyl 4- (5-aminopyridin-2-yloxy) benzoate (16.0 g, 62 mmol) was dissolved in toluene (300 raL). To the resulting solution were added 4-trifluoromethylacetophenone (11.7 g, 62 mmol) and (±) -camfor-10-sulfonic acid (1.08 g, 4.65 mmol), and refluxed overnight. The reaction solution was concentrated under reduced pressure, thereby producing 26.5 g of the title compound. Appearance: Dark green oil RNM (CDC13) d 1.35-1.41 (3H, ra), 2.34 (3H, s), 4.36 (2H, d, J = 7.1 Hz), 7.01- .31 (4H, m), 7.70- 7.77 (3H, m), 8.01-8.11 (4H, m).

Reference Example 613 Production of 4- (5- [(4-Trifluoromethylbenzylidene) -amino] pyridin-2-yloxy methyl benzoate ( 2.64 g, 6.59 mmol) was suspended in methanol (25 mL), and sodium borohydride (1.25 g, 33.0 mmol) was added slowly to the resulting suspension.The resulting solution was stirred at room temperature for 3 days. concentrated under reduced pressure, ethyl acetate was added to the residue, and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was washed with diethyl ether, to thereby yield 2.65 g of the title compound. Appearance: White powder XH NMR (CDC13) d 3.89 (3H, s), 4.16 (1H, brs), 4.42 (2H, s), 6.84 (1H, d, J = 8.7 Hz), 7.01 (1H, dd, J = 8.6 Hz, 3.0 Hz), 7.05 (2H, d, J = 8.4 Hz), 7.49 (2H, d, J = 8.4 Hz), 7.62 (2H, d, J = 8.3 Hz), 7.67 (1H, d, J = 3.1 Hz), 8.01 (2H, d, J = 8.6 Hz). The following compounds were produced in the same manner as in Reference Example 613.

Reference Example 618 Production of 3-. { 4- [5- (3,4-dichlorobenzylamino) -pyridin-2-yloxy] phenyl} ethyl propionate A solution of 3,4-dichlorobenzaldehyde (1.28 g, 7.3 ramol) was added to a solution of ethyl 3- [4- (5-aminopyridin-2-yloxy) phenyl] propionate (2.1 g, 7.3 mmol) in ethanol (20 mL), and the resulting solution was stirred for 2 hours at 40 ° C. To the resulting reaction solution was added sodium borohydride (0.55 g, 15.7 mmol) under cooling with ice, and stirred at the same temperature for 1 hour. Water was added to the solution and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 4: 1), to thereby yield 2.71 g of the title compound. Appearance: Colorless oil? U RNM (CDC13) d 1.24 (3H, t, J = 7.1 Hz), 2.50-2.68 (2H, m), 2.81-3.01 (2H, m), 3.71-4.20 (3H, m), 4.28 (2H, s), 6.76 (1H, d, J = 8.7 Hz), 6.88-7.02 (3H, m), 7.06-7.23 (3H, m), 7.41 (1H, d, J = 8.2 Hz), 7.46 (1H, d, J = 2.0 Hz), 7.60 (1H, d, J = 3.0 Hz). The following compounds were produced in the same manner as in Reference Example 618.

Table 90 Reference Example 628 Production of ethyl 3- (4-. {5- [benzyloxycarbonyl (2-methoxyethyl) araino] pyridin-2-yloxy} phenyl) propionate Under a nitrogen atmosphere, to a solution of [Ethyl 4- (5-benzyloxycarbonylaminopyridin-2-yloxy) phenyl] propionate (1.7 g, 4.0 mmol) in DMF (50 mL) was added 60% sodium hydride (0.19 g, 4.9 mmol) under ice-cooling, and the resulting solution was stirred for 35 minutes at the same temperature. 2-Bromoethylmethyl ether (0.4 mL, 4.2 mmol) was added dropwise to the solution. The reaction solution was stirred for 2 hours under cooling with ice, and then stirred for 2 days at room temperature. To the reaction solution was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel. (.n-hexane: ethyl acetate = 4: 1), to thereby produce 1.6 g of the title compound. Appearance: Pale yellow oil? U RNM (CDC13) d 1.25 (3H, t, J = 7.1 Hz), 2.57-2.70 (2H, ra), 2.89-3.02 (2H, m), 3.52 (2H, t, J = 5.4 Hz), 3.79 (2H, t, J = 5.4 Hz), 4.14 (2H, q, J = 7.1 Hz), 5.14 (2H, brs), 6.87 (1H, d, J = 8.7 Hz), 6.89-7.10 (2H, m), 7.11-7.41 (7H, m), 7.47-7.69 (ÍH, m), 8.10 (1H, brs).

The following compounds were produced in the same manner as in Reference Example 628.

Reference Example 629 [(4- {5- [(3,4-Dichlorophenyl) methylamino] pyridin-2-yloxy} -2-trifluoromethylphenyl) ethylamino] ethyl acetate MS 541 (M " Table 91 Reference Example 636 Production of 3-. { 4- [5- (2-methoxyethylamino) -pyridin-2-yloxy] phenyl} ethyl propionate To a solution of 3- (4- {5- [benzyloxycarbonyl (2-methoxyethyl) amino] pyridin-2-yloxy} phenyl} ethyl propionate (1.82 g, 3.8 mmol) in ethanol-ethyl acetate (10 mL-10 mL) was added under an atmosphere of palladium-carbon nitrogen to the % (0.2 g), and the resulting solution was stirred for 3 hours under an atmosphere of hydrogen at atmospheric pressure. He Palladium-carbon was filtered through Celite, and the filtrate was evaporated to yield 1.23 g of the title compound. Appearance: Blue oil RNM (CDC13) d 1.24 (3H, t, J = 7.1 Hz), 2.55- 2.68 (2H, ra), 2.87-2.98 (2H, m), 3.20-3.31 (2H, m), 3.56- 3.66 (2H, m), 4.13 (2H, q, J = 7.1 Hz), 6.77 (1H, d, J = 8.7 Hz), 6.93-7.0K2H, m), 7.03 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.13-7.22 (2H, m), 7.66 (ÍH, d, J = 3.0 Hz). The following compound was produced in the same manner as in Reference Example 636.

Reference Example 637 ethyl 3- [4- (5-ethylaminopyridin-2-yloxy) phenyl] -propionate RNM (CDCl 3) d 1.29-1.32 (6H, m), 2.55-2.67 (2H, m), 2.87-2.99 (2H, m), 3.14 (2H, q, J = 7.1 Hz), 4.13 (2H, q, J = 7.1 Hz), 6.77 (1H, d, J = 8.7 Hz), 6.89-7.02 (3H, m) , 7.09-7.25 (3H, m), 7.63 (ÍH, d, J = 3.0 Hz).

Reference Example 638 Production of ethyl 3- (3-methoxy-4-. {5 - [methyl- (4-trifluoromethylbenzyl) amino] pyridin-2-yloxy} phenyl) -propionate To a solution of 3- . { 3-methoxy-4- [5- (- trifluoromethylbenzylamino] pyridin-2-yloxy} phenyl } Ethylpropionate (0.8 g, 1.7 mmol) in methanol (15 mL) was added a solution of 37% aqueous formaldehyde (0.38 mL, 5.1 mmol) and acetic acid (0.1 mL, 1.7 mmol). The reaction solution was stirred for 30 minutes at room temperature. After this, sodium cyanoborohydride, (0.24 g, 3.4 mmol) was added to the reaction solution under ice-cooling, and the mixture was stirred under ice-cooling for 40 minutes. Water was added to the reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 4: 1), to thereby yield 0.62 g of the title compound. Appearance: Pale yellow oil? U RNM (CDC13) d 1.25 (3H, t, J = 7.1 Hz), 2.52-2.70 (2H, m), 2.87-3.02 (5H, m), 3.77 (3H, s), 4.14 (2H, q, J = 7.1 Hz), 4.40-4.50 (2H, m), 6.74-6.86 ((3H, ra), 6.97 (1H, d, J = 8.0 Hz), 7.1K1H, dd, J = 8.9 Hz, 3.2 Hz), 7.34 (2H, d, J = 8.1 Hz), 7.57 (2H, d, J = 8.1 Hz), 7.65 (1H, d, J = 3.2 Hz). The following compounds were produced in the same manner as in Reference Example 638.

Table 92 Table 93 Table 94 Reference Example 656 Production; of ethyl 3- (4- (5- (3, 4-dichlorophenylamino) pyridin-2-yloxy) phenyl) propionate. Triethylamine (1.2 mL, 8.4 ramol) was added to a suspension of 3- (4- (5-aminopyridine). Ethyl-2-yloxy) phenyl) propionate (1.2 g, 4.2 mmol), 3,4-dichlorophenylboronic acid (1.6 g, 8.4 mmol), anhydrous copper acetate (0.762 g, 4.2 mmol) and 4A molecular sieves (5 g ) in dichloromethane (24 mL), and the resulting reaction solution was stirred overnight at room temperature. After the resulting solution was filtered through Celite, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (n-hexane: ethyl acetate = 4: 1), to thereby produce 1.5 g of the title compound. Appearance: Light brown coffee XU RNM (CDC13) d 1.25 (3H, t, J = 7.1 Hz), 2.60-2.66 (2H, m), 2.93-2.99 (2H, m), 4.14 (2H, q, J = 7.1 Hz), 5.52 (1H, brs), 6.71 (1H, dd, J = 8.7 Hz, 2.7 Hz), 6.90 (1H, d, J = 8.7 Hz), 6.97 (1H, d, J = 2.7 Hz), 7.04 -7.08 (2H, m), 7.21-7.26 (3H, m), 7.49 (1H, dd, J = 8.7 Hz, 2.9 Hz), 8.01 (1H, d, J = 2.8 Hz). The following compound was produced in the same manner as in Reference Example 656.

Reference Example 657 ( { 4- [5- (3, -Dichlorophenylamino) pyridin-2-yloxy] -2-trifluoromethylphenyl} ethylaraine) ethyl acetate MS 527 (M +).

Reference Example 658 Production of Ethyl 4- [3- (4-benzyloxy-3-methyl) phenyl-2-oxotetrahydropyriraidin-1-yl] benzoate Under a nitrogen atmosphere, to a solution of 1- (4-benzyloxy) 3-methyl) phenyltetrahydropyrimidin-2-one (0.5 g, 1. 7 mmol) in dioxane (5 mL) was added copper iodide (I) (16 mg, 0.08 mmol) and N, N-dimethylglycine hydrochloride (47 mg, 0. 34 mmol). The resulting solution was stirred for 5 minutes, and then ethyl 4-iodobenzoate (0.39 g, 1.4 mmol) and potassium phosphate (III) (1.04 g, 4.9 mmol) were added to the reaction mixture. The resulting solution was stirred for 20 hours at 100 ° C, after which the resulting solution was sprayed with silica gel. The residue was purified by chromatography on silica gel (n-hexane: ethyl acetate = 3: 1 - »dichloromethane: methanol = 40: 1), to thereby yield 0.43 g of the title compound. Appearance: Powder white XU RNM (DMSO-d6) d 1.30 (3H, t, J = 7.1 Hz), 2.08-2.22 (5H, m), 3.66 (2H, t, J = 5.9 Hz), 3.81 (2H, t , J = 5.9 Hz), 4.28 (2H, q, J = 7.1 Hz), 5.10 (2H, s), 6.86-7.14 (3H, m), 7.26- 7. 51 (7H, m), 7.82-7.92 (2H, m).

Reference Example 659 Production of ethyl (E) -3- (3-Raetoxy-4- { 5- [2- (4-trifluorora-ethylphenyl) vinyl] pyridin-2-yloxy} phenyl) propionate A 3- [Ethyl 4- (5-bromopyridin-2-yloxy) -3-methoxyphenyl] propionate (610 mg, 1.6 mmol) were added 4-trifluoromethylstyrene (0.332 raL, 2.2 mmol), dichlorobis (benzonitril) -palladium (II) (33 mg, 0.082 mmol), N, N-dimethylglycine hydrochloride (17 mg, 0.16 mmol), acetate of sodium (263 mg, 3.2 mmol) and N-methylpyrrolidone (5 mL) under an argon atmosphere. The resulting solution was stirred under an argon atmosphere for 17 hours at 130 ° C. To the reaction solution was added ethyl acetate and filtered. The filtrate was washed with water, and then dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 3: 1), to thereby produce 500 mg of the title compound. Appearance: Pale yellow oil U RNM (CDC13) d 1.27 (3H, t, J = 7.1 Hz), 2.64-2.69 (2H, m), 2.95-3.01 (2H, m), 3.76 (3H, s), 4.05 ( 2H, q, J = 7.1 Hz), 6.71-6.88 (2H, m), 6.95 (1H, d, J = 8.6 Hz), 6.98-7.08 (2H, ra), 7.11 (1H, d, J = 16.5 Hz ), 7.56-7.63 (4H, m), 7.87- 7. 91 (1H, m), 8.23 (1H, d, J = 2.3 Hz). The following compound was produced in the same manner as in Reference Example 659.

Reference Example 660 3- (4-. {5 - [(E) -2- (3,4-Dichlorophenyl) vinyl] pyridin-2-yloxy}. 3-methoxyphenyl) ethyl propionate XU NMR (CDC13 ) d 1.26 (3H, t, J = 7.1 Hz), 2.63-2.69 (2H, m), 2.94-3.00 (2H, m), 3.76 (3H, s), 4.15 (2H, q, J = 7.1 Hz) , 6.81-6.90 (3H, m), 6.93 (1H, d, J = 8.6 Hz), 6.99 (1H, d, J = 15.3 Hz), 7.06 (1H, d, J = 9.1 Hz), 7.27-7.31 ( ÍH, ra), 7.40 (1H, d, J = 8.2 Hz), 7.55 (1H, d, J = 2.0 Hz), 7.82-7.86 (1H, m), 8.19 (1H, d, J = 2.'5 Hz).

Reference Example 661 Production of. { - [4- (3, -dichlorobenzoylaraine) -2-fluorophenoxy] benzenesulfonyl} ethyl acetate To a solution of (4- [4- (3, 4-dichlorobenzoylamino) 2-fluorophenoxy] phenylsulfanyl} -acetic acid ethyl ester (1.20 g, 2.43 mmol) in dichloromethane (20 mL) was added chloroperbenzoic acid (1.45 g, 6.06 mmol) at 0 ° C. The resulting solution was stirred for 2 hours at room temperature, methanol was added to the reaction solution and stirred for some time, water was added to the resulting solution, and It was extracted with dichloromethane. dichloromethane was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and evaporated. The residue obtained was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 1), thereby producing 1.28 g of the title compound. Appearance: Amorphous yellow powder XU RNM (CDC13) d 1.22 (3H, t, J = 7.1 Hz), 4.11 (2H, s), 4.16 (2H, q, J = 7.1 Hz), 7.06 (2H, d, J = 8.9 Hz), 7.19 (1H, t, J = 8.7 Hz), 7.30 (1H, d, J = 8.7 Hz), 7.59 (1H, d, J = 8.3 Hz), 7.71 (1H, dd, J = 2.0 Hz , 8.3 Hz), 7.75-7.85 (HI, m), 7.86-7.95 (3H, m), 7.98 (1H, d, J = 2.0 Hz).

Reference Example 662 Production of 3-. { 4- [5- (3,4-dichlorobenzoyl-araino) pyridin-2-sulfinyl] phenyl} methyl propionate To a solution of methyl 3- (4- [5- (3, 4-dichlorobenzoylamino) pyridin-2-ylsulphane] phenyl-J-propionate (1.00 g, 2.17 mmol) in dichloromethane (20 mL) was added m-acid. chloroperbenzoic acid (0.620 g, 2.60 mmol) at 0 ° C. The resulting solution was stirred for 1 hour at 0 ° C. Methanol was added to the reaction solution and stirred for some time, water was added to the resulting solution, and extracted with dichloromethane.The dichloromethane layer was washed with water, a bicarbonate solution of saturated sodium and brine, dried over anhydrous sodium sulfate, and evaporated. The residue obtained was recrystallized from ethanol 3 times, to thereby produce 0.790 g of the title compound. Appearance: White powder Melting point: 164-166 ° C Reference Example 663 Production of 3-. { 4- [5- (3,4-dichlorobenzoyl-araino) pyridin-2-sulfonyl] phenyl} Methyl propionate To a solution of 3-. { 4- [5- (3,4-dichlorobenzoylamino) pyridin-2-ylsulphane] phenyl} Methyl propionate (1.00 g, 2.17 mmol) in dichloromethane (20 μL) was added m-chloroperbenzoic acid (1.29 g, 5.42 mmol) at 0 ° C. The resulting solution was stirred for 1.5 hours at 0 ° C. Methanol was added to the reaction solution and stirred for some time. To the resulting solution was then added water, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The obtained residue was recrystallized from ethanol, in order to produce 0.890 g of the title compound. Appearance: White powder Melting point: 165-166 ° C Reference Example 664 Production of. { 4- [4- (3,4-dichlorobenzoylamino) -2-fluorophenoxy] benzenesulfenyl} ethyl acetate To a solution of. { - [- (3,4-dichlorobenzoylamino) -2-fluorophenoxy] phenylsulfanyl ethyl acetate (0.800 g, 1.61 mmol) in methanol (20 mL) was added a solution of 31% hydrogen peroxide (2.08 mL, 18.5 mmol) . The resulting solution was refluxed for 16 hours. The reaction solution was cooled with ice, and the resulting precipitated solid was collected by filtration, to thereby yield 0.651 g of the title compound. Appearance: XU white powder RNM (DMSO-d6) d 1.13 (3H, t, J = 7.1 Hz), 3.90-4.10 (4H, m), 7.14 (2H, d, J = 8.8 Hz), 7.34 (1H, t , J = 9.0 Hz), 7.55-7.65 (ÍH, m), 7.72 (2H, d, J = 8.8 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.90-8.00 (2H, m), 8.22 (1H, d, J = 2.0 Hz), 10.63 (1H, s).

Reference Example 665 Production of ethyl 3- (4-. {5- [4- (trifluoromethyl) phenyl-carbamoyl] pyridin-2-yloxy} phenyl) butyrate To a suspension of 60% sodium hydride ( 0.133 g, 3.3 mmol) in THF (6 mL) was added dropwise triethylphosphonyl acetate (0.53 mL, 2.7 mmol) under ice-cooling, and the resulting solution was stirred for 1 hour at room temperature. To the reaction solution was added a solution of 6- (4-acetylphenoxy) -N- [4- (trifluoromethyl] phenyl] nicotinamide (0.53 g, 1.3 mmol) in THF (6 mL), and the resulting solution was stirred for 10 hours at 60 ° C. The reaction solution was added saturated aqueous ammonium chloride, and extracted with ethyl acetate.The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by chromatography over silica gel (n-hexane: ethyl acetate = 4: 1), to produce 0.57 g of the intermediate product 3- (4-. {5- [4- (trifluoromethyl) phenylcarbamoyl] pyridin-2-yloxy) phenyl) -2-butenoate, 10% palladium-carbon (0.057 g) was suspended in a mixed solvent consisting of ethanol (8 mL) and dioxane (2 mL), and this suspension was added 3- (4- {5- [4- (trifluoromethyl) -phenylcarbamoyl] pyridin-2-yloxy} phenyl) -2-ethyl butenoate (0.57 g, 1.2 mmol) The resulting product was subjected to catalytic reduction. at atmospheric pressure and room temperature. Once the absorption of the hydrogen was stopped, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, to thereby yield 0.56 g of the title compound. Appearance: White solid XU RNM (CDC13) d 1.21 (3H, t, J = 7.1 Hz), 1.33 (3H, d, J = 7.0 Hz), 2.51-2.67 (2H, m), 3.28-3.37 (ÍH, m ), 4.10 (2H, q, J = 7.1 Hz), 7.00 (1H, d, J = 8.6 Hz), 7.07-7.12 (2H, m), 7.26- 7. 3K2H, m), 7.60-7.65 (2H, ra), 7.73-7.77 (2H, m), 7.81 (1H, brs), 8.21 (1H, dd, J = 8.6, 2.6 Hz), 8.68 (1H, d, J = 2.3 Hz). The following compound was produced in the same manner as in Reference Example 665.

Reference Example 666 2-methyl-3-. { 4- [5- (4-trifluoromethylphenyl-carbamoyl)? Iridin-2-yloxy] phenyl} Ethyl propionate MS 472 (M +) Reference Example 667 Production of 3,4-dichloro-N-. { 6- [4- (N-hydroxy-carbamimidoylmethyl) phenoxy] pyridin-3-yl} Benzaraide To a solution of 3,4-dichloro-N- [6- (4-cyanomethylphenoxy) pyridin-3-yl] benzamide (700 mg, 1.76 mmol) in ethanol (30 mL) was added water (2 mL), hydroxylamine (420 mg, 12.71 mmol) and potassium carbonate (1.76 g, 12.73 mmol). Under argon, the resulting solution was stirred under reflux for 4 hours. The resulting reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (dichloromethane: methanol = 10: 1), to thereby produce 510 mg of composed of the title. Appearance: White Powder XU RNM (DMSO-d6) d 3.27 (2H, s), 5.41 (2H, brs), 7. 03 (2H, d, J = 8.4 Hz), 7.05 (1H, d, J = 8.8 Hz), 7.31 (2H, d, J = 8.4 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.94 ( 1H, dd, J = 8.4 Hz, 2. 0 Hz), 8.18 (1H, dd, J = 8.8 Hz, 2.6 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.46 (1H, d, J = 2.6 Hz), 8.88 (1H, s), 10.53 (1H, s).

Reference Example 668 Production of 3,4-dichloro-N-. { 6- [4- (N-Acetoxy-carbamimidoylmethyl) phenoxy] pyridin-3-yl} benzamide To a solution of 3,4-dichloro-N-. { 6- [4- (N-hydroxycarbamimidoylmethyl) phenoxy] pyridin-3-ylbenzamide (510 mg, 1.18 mmol) in dioxane (8 mL) was added potassium carbonate (163 mg, 1.18 mmol). While stirring under cooling with ice, acetyl chloride (0.084 mL, 1.18 mmol) was added dropwise to the resulting solution, and the resulting solution was stirred for 15 minutes at room temperature. To the reaction solution was added THF (10 mL), then water, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated. The residue was washed with ethyl acetate to yield 340 mg of the title compound. Appearance: White powder U RNM (DMSO-dg) d 2.05 (3H, s), 3.35 (2H, s), 6.43 (2H, brs), 7.06 (1H, d, J = 9.0 Hz), 7.06 (2H, d, J = 8.6 Hz), 7. 36 (2H, d, J = 8.6 Hz), 7.84 (1H, d, J = 8.3 Hz), 7.94 (1H, dd, J = 8.3 Hz, 2.0 Hz), 8.18 (1H, dd, J = 9.0 Hz, 2.5 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.47 (1H, d, J = 2.5 Hz), 10.54 ( 1 HOUR, Reference Example 669 Production of acid 4-. { 4- [4- (3,4-dichlorobenzoylamino) -2-fluorophenoxy] phenyl} -4-oxobutyric To a suspension consisting of 3, -dichloro-3'-fluoro-4'-phenoxybenzanilide (5.05 g, 13.4 mmol) and succinic anhydride (1.48 g, 14.8 mmol) in 1,2-dichloroethane (25 mL) ) aluminum chloride (6.26 g, 47.0 mmol) was added under cooling with ice, and the resulting mixture was stirred at the same temperature for 5 minutes, and then at room temperature for 1.5 hours. The resulting reaction solution was poured into ice water, and the resulting solid was collected by filtration. To the solid was added 50% aqueous acetone (200 mL), and the resulting solution was refluxed for 0.5 hour, then cooled. The solid obtained was collected by filtration, in order to produce 6.30 g of the title compound. Appearance: White powder Melting point: 205-208 ° C Reference Example 670 Production of 3-. { 4- [hydroxy (5-nitro-2-pyridyl) -ramethyl] phenyl} ethyl propionate To a solution of ethyl 3- [4- (5-nitropyridine-2-carbonyl) phenyl] propionate (1.52 g, 4.63 mmol) in dichloromethane (15 mL) and ethanol (15 mL) was added sodium borohydride (0.175 g, 4.63 mmol) under cooling with ice, and the resulting solution was stirred at the same temperature for 1 hour. The reaction solution was concentrated under reduced pressure. The residue was dissolved in water and ethyl acetate. To the solution was added acetic acid and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane ethyl racetate = 3: 1), to thereby yield 0.264 g of the title compound. Appearance: Brown coffee powder RNM (CDC13) d 1.19 (3H, t, J = 7.2 Hz), 2.56 (2H, t, J = 7.8 Hz), 2.91 (2H, t, J = 7.8 Hz), 4.09 (2H, q, J = 7.2 Hz), 4.35 (1H, brs), 5.84 (1H, s), 7.17 (2H, d, J = 8.1 Hz), 7.26 (2H, d, J = 8.1 Hz), 7.46 (1H, d, J = 8.7 Hz), 8.40 (1H, dd, J = 8.7 Hz, 2.5 Hz), 9.36 (1H, d , J = 2.5 Hz). 1 The following compound was produced in the same manner as in Reference Example 670.

Reference Example 671 4- [2-Hydroxy-3- (4-hydroxyphenyl) propionyl] -piperazine-1-carboxylate of t-butyl XU NMR (CDC13) d 1.47 (9H, s), 1.62 (1H, brs), 2.85 (2H, d, J = 6.0 Hz), 3.00-3.80 (8H, m), 4.56 (1H, t, J = 6.0 Hz), 5.35 (1H, brs), 6.74 (2H, d, J = 8.4 Hz ), 7.06 (2H, d, J = 8.4 Hz).

Reference Example 672 Production of ethyl 3- (4-. {5- (bis (3,4-dichlorobenzoyl) -amino] -2-pyridylmethyl} phenyl) propionate To a 10% palladium-carbon suspension (27 mg) in ethanol (5 mL) were added a solution of 3-. { 4- [Ethyl hydroxy (5-nitro-2-pyridyl) -methyl] phenyl Jpropionate (0.264 g, 0.799 mmol) and 0.5 M hydrogen chloride in ethanol (2 mL), and the resulting solution was subjected to catalytic reduction atmospheric pressure at 50 ° C. Once the absorption of the hydrogen was stopped, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was suspended in THF (5 mL), and triethylamine (0.267 mL, 2.40 mmol) was added. To the solution was added dropwise a solution of 3,4- chloride. dichlorobenzoyl (0.255 g, 0.879 mmol) in THF (1 mL) under ice-cooling, and stirred for 1 hour at the same temperature. To the resulting solution, water was added and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 5: 1), to thereby produce 0.177 g of the title compound. Appearance: Pale yellow oil XH RNM (CDC13) d 1.20 (3H, t, J = 7.2 Hz), 2.56 (2H, t, J = 7.8 Hz), 2.89 (2H, t, J = 7.8 Hz), 4.09 (2H , q, J = 7.2 Hz), 6.99 (1H, s), 7.17 (2H, d, J = 8.2 Hz), 7.35 (2H, d, J = 8.2 Hz), 7.42 (1H, d, J = 8.6 Hz ), 7.43-7.56 (2H, m), 7.63 (1H, dd, J = 8.6 Hz, 2.1 Hz), 7.85-7.9 (2H, m), 8.15 (1H, d, J = 2.0 Hz), 8.20-8.32 (2H, ra), 8.57 (1H, d, J = 2.5 Hz).

Reference Example 673 Production of ethyl 3- (4- (5- (N- (4- (trifluoromethyl) -phenyl) sulpharaoyl) pyridin-2-yloxy) phenyl) propionate To a solution of 3- (4- (3 -bromo-5- (N- (4- (trifluoromethyl) phenyl) sulfamoyl) pyridin-2-yloxy) phenyl) propionate (0.41 g, 0.7 mmol) in ethanol (10 mL) were added 10% palladium-carbon (0.041 g) and formate Ammonium (0.226 g, 3.6 mmol), and the resulting solution was heated to reflux for 2 hours. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was then purified by chromatography on silica gel (n-hexane ethyl acetate = 4: 1), to thereby yield 0.28 g of the title compound. Appearance: White solid XU RNM (CDC13) d 1.24 (3H, t, J = 7.1 Hz), 2.60-2.66 (2H, m), 2.93-2.99 (2H, m), 4.14 (2H, q, J = 7.1 Hz ), 6.95 (1H, d, J = 8.8 Hz), 7.01- .05 (2H, m), 7.20-7.26 (3H, m), 7.50-7.54 (3H, m), 8.03 (1H, dd, J = 8.8 Hz, 2.6 Hz), 8.59 (1H, d, J = 2.6 Hz).

Reference Example 674 Production of 1- (4-Raetoxyphenyl) iraidazolin-2-one To a suspension of 1- (2-chloroethyl) -3- (4-methoxyphenyl) urea (7.0 g, 30.6 mmol) in t-butanol ( 120 mL) was added potassium t-butoxide (6.4 g, 57.0 mmol) under a nitrogen atmosphere. The resulting solution was stirred for 10 minutes, and then potassium t-butoxide was added. (3.0 g, 26.7 mmol). This solution was stirred for 10 minutes, and then potassium t-butoxide (4.3 g, 38.3 mmol) was added. The resulting solution was stirred for 16 hours at room temperature. The pH was adjusted to between 2 and 3 with acid % hydrochloric acid, and the solvent was evaporated under reduced pressure. Water (100 mL) and ethyl acetate (100 mL) were added to the residue, and it was stirred for 1 hour at room temperature. The resulting precipitates were filtered, washed with diethyl ether, and then dried under reduced pressure, to thereby yield 5.1 g of the title compound. Appearance: White powder XU NMR (DMSO-d6) d 3.29-3.44 (2H, m), 3.70 (3H, s), 3.71-3.88 (2H, m), 6.77 (1H, s), 6.81-6.95 (2H, m), 7.35-7.50 (2H, m). The following compounds were produced in the same manner as in Reference Example 674.

Reference Example 675 1- (4-Benzyloxy-3-methylphenyl) tetrahydropyriraidin-2-one RNM (DMSO-d6) d 1.81-1.96 (2H, m), 2.16 (3H, s), 3. 11-3.25 (2H, m), 3.51 (2H, t, J = 5.6 Hz), 5.09 (2H, s), 6.42 (1H, s), 6.91 (1H, d, J = 8.7 Hz), 6.98 (1H , dd, J = 2.6 Hz, 8. 7 Hz), 7.04 (1H, d, J = 2.6 Hz), 7.28-7.34 (HH, m), 7.36-7.41 (2H, m), 7.42-7.48 (2H, m).

Table 95 Table 96 Reference Example 682 Production of acid 3-. { 4- [4- (3,4-dichlorobenzoylamino) -phenoxy] phenyl} propionic To a solution of 3-. { 4 - [4 - (3,4-dichlorobenzoi lamino) phenoxy] phenyl} Ethyl propionate (6.00 g, 13.1 mmol) in THF (60 mL) and ethanol (30 mL) were added 5 M aqueous sodium hydroxide (3.14 mL, 15.7 mmol) and water (30 mL) and the resulting solution was subjected to reflux for 1 hour. The reaction solution was cooled with ice. To the reaction solution were added 5 M hydrochloric acid (4.0 mL, . 0 mmol) and water (100 mL). The solid obtained was collected by filtration, and recrystallized from acetone containing water, to thereby produce 5.60 g of the title compound. Appearance: White powder Melting point: 188-190 ° C The following compounds were produced in the same manner as in Reference Example 682.

Table 97 Table 98 Table 99 Table 100 Table 101 Table 102 0 (-SO- means a group of I1I1 and -S02- meaning or., P group of ~. Henceforth in the present -SO- and -S02- indicate the same meanings) Table 103 Table 104 Table 105 15 twenty Table 106 Table 107 Table 108 Table 109 Table 110 Table 111 Table 112 Table 113 Table 114 Table 115 Table 116 Table 117 Reference Example 857 Production of acid 3-. { 4- [5- (3,4-dichlorobenzylmethylamino) -pyridin-2-yloxy] phenyl} propionic To a solution of 3-. { 4- [5- (3,4-dichlorobenzylamino) pyridin-2-yloxy] phenyl ethyl J-propionate (1.63 g, 3.7 mmol) in ethanol (30 mL) were added 37% aqueous formaldehyde (2.0 mL, 22 mmol) and acetic acid (0.21 mL, 3.7 mmol), and the resulting solution was stirred at room temperature for 1 hour . To this solution was then added sodium cyanoborohydride (0.46 g, 7.3 mmol) at 0 ° C, and the resulting solution was stirred at the same temperature for 1 hour. To this solution, water was added and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. He The solvent was evaporated, and the residue was purified by column chromatography on silica gel (.n-hexane: ethyl acetate = 5: 1), to thereby produce 1.55 g of 3-. { 4- [5- (3,4-dichlorobenzylmethylamino) -pyridin-2-yloxy] phenyl ethyl J-propionate. This product was dissolved in ethanol (40 mL), and to the resulting solution was added 10% aqueous sodium hydroxide (2.7 mL, 6.7 mmol) and stirred at room temperature for 2 hours. The resulting solution was then acidified by adding 10% hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated, thereby yielding 1.44 g of the title compound. Appearance: Colorless oil XU NMR (DMSO-d6) d 2.38-2.60 (2H, m), 2.78 (2H, t, J = 7. 6 Hz), 4.52 (2H, s), 6.81-6.92 (3H, m), 7.12-7.23 (3H, ra), 7.28 (1H, dd, J = 8.9 Hz, 3.3 Hz), 7.48 (1H, d, J = 1.9 Hz), 7.57 (1H, d, J = 8.2 Hz), 7.63 (1H, d, J = 3.3 Hz), 11.70-12.40 (1H, m). The following compound was produced in the same manner as in Reference Example 857.

Reference Example 858 3- (4-. {5 - [(3,4-Dichlorobenzyl) ethylamino] pyridin-2-yloxy} phenyl) propionic acid NMR (DMSO-ds) d 1.09 (3H, t, J = 6.9 Hz), 2.37-2.59 (2H, m), 2.64-2.83 (2H, m), 3.45 (2H, q, J = 6.9 Hz), 4. 48 (2H, s), 6.82 (1H, d, J = 8.9 Hz), 6.85-6.92 (2H, m), 7.12- 7.25 (4H, m), 7.48 (1H, d, J = 1.8 Hz), 7.54 -7.61 (2H, m), 11.77-12.38 (ÍH, m).

Reference Example 859 Production of N- [2- (4-formylphenoxy) -5-pyridyl] -3,4-dichlorobenzamide To a solution of acetalethylene 4- [(5-amino-2-pyridyl) oxy] benzaldehyde (5.27 g , 20.4 mmol) and triethylamine (3.41 mL, 24.5 mmol) in THF (80 mL) was added dropwise a solution of 3,4-dichlorobenzoyl chloride (4.49 g, 21.4 mmol) in THF (30 mL) under ice-cooling . The resulting solution was stirred for 2 hours at the same temperature. The reaction solution was concentrated under reduced pressure, to the residue, 80% acetic acid (55 mL) was added, and the mixture was heated to 80 ° C with stirring for 1 hour. The reaction solution was concentrated under reduced pressure and water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over magnesium sulfate anhydrous, and evaporated. The solid obtained was recrystallized from isopropanol, thereby producing 5.63 g of the title compound. Appearance: Powder pale yellow XU RNM (CDC13) d 7.05 (1H, d, J = 8.7 Hz), 7.24 (2H, d, J = 8.7 Hz), 7.57 (1H, d, J = 8.4 Hz), 7.70 (1H, dd, J = 8.4 Hz, 2. 1 Hz), 7.82-7.93 (3H, m), 7.97 (1H, d, J = 2.1 Hz), 8.25 (1H, dd, J = 8.7 Hz, 2.7 Hz), 8.29 (1H, d, J = 2.7 Hz ), 9.96 (1H, s).

Reference Example 860 Production of. { 4- [5- (3,4-dichlorobenzoylaraine) -pyridin-2-yloxy] benzylaraine} ethyl acetate A solution of N- [2- (4-formylphenoxy) -5-pyridyl] -3, -dichlorobenzamide (1.00 g, 2.58 mmol), glycine ethyl ester hydrochloride (0.400 g, 2.84 mmol) and ethyl acetate sodium (0.230 g, 2.84 mmol) in methanol (20 mL) was stirred for 30 minutes at 60 ° C. The reaction solution was cooled with ice, and then sodium cyanoborohydride (0.180 g, 2.84 mmol) was added. The resulting solution was stirred at the same temperature for 1 hour. To the reaction solution was added 5 M hydrochloric acid (2 mL) and concentrated under reduced pressure. A solution of saturated sodium bicarbonate was added to the residue, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 2), to thereby produce 0.752 g of the title compound. Appearance: Yellow oil XU RNM (CDC13) d 1.27 (3H, t, J = 7.1 Hz), 3.43 (2H, s), 3.81 (2H, s), 4.20 (2H, q, J = 7.1 Hz), 6.95 ( 1H, d, J = 8.8 Hz), 7.09 (2H, d, J = 8.5 Hz), 7.36 (2H, d, J = 8.5 Hz), 7.57 (1H, d, J = 8.3 Hz), 7.71 (1H, dd, J = 2.1 Hz, 8.3 Hz), 7.84 (1H, s), 7.98 (1H, d, J = 2.1 Hz), 8.18 (1H, dd, J = 2.7 Hz, 8.8 Hz), 8.24 (1H, d , J = 2.7 Hz).

Reference Example 861 Production of (acetyl- {4- [5- (3,4-dicJorobenzoylamino) pyridin-2-yloxy] benzyl] aracetic acid) acetic acid To a solution of. { Ethyl 4 - [5- (3, 4-dichloro-benzoylamino) pyridin-2-yloxy] benzylane) acetate (0.811 g, 1.59 mmol) in dichloromethane (5 mL) were added triethylamine (0.332 mL, 2.39 mmol) and acetyl chloride (0.136 mL, 1.91 mraol) at room temperature. The resulting solution was stirred for 1 hour at the same temperature. To the reaction solution was added water, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated, yielding 0.785 g of residue.

This residue was dissolved in ethanol (5 mL). To the resulting solution was added 5 M aqueous sodium hydroxide (0.350 mL, 1.75 mmol) at room temperature and stirred at the same temperature for 14 hours. To the resulting reaction solution were added 5 M hydrochloric acid (0.400 raL) and water, and extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated, yielding 0.776 g of the title compound. Appearance: White amorphous powder XU RNM (DMSO-ds at 375 K) d 2.10 (3H, s), 4.02 (2H, s), 4.60 (2H, s), 7.03 (1H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.2 Hz), 7.32 (2H, d, J = 8.2 Hz), 7.78 (1H, d, J = 8.4 Hz), 7.97 (1H, dd, J = 2.1 Hz, 8.4 Hz), 8.10-8.30 (2H, m), 8.53 (1H, d, J = 2.6 Hz), 10.23 (1H, s).

Reference Example 862 Production of 1- (4-piperoni Ipipera z in- 1-i 1) -2-. { methyl- [3-methyl-4- (5-nitropyridin-2-yloxy) phenyl] amino} -etanone To an acid solution. { met il [3-met il- - (5-ni t ropi r idin-2-i loxi) feni 1] amino} acetic acid (0.93 g, 2.9 mmol) in DMF (40 mL) were added 1-ethylhydrochloride 3- (3-dimet i larainopropi 1) carbodiimide (0.67 g, 3.5 mmol), monohydrate 1 -hydroxybenzot zol ria (0.54 g, 3.5 mmol), and 1-piperonylpiperazine (0.68 g, 3.08 mmol). The reaction mixture was stirred for 15 hours at room temperature under a nitrogen atmosphere. To the resulting solution, water was added and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 2: 1-dichloromethane: methanol = 100: 1), to thereby produce 1.2 g of the title compound. Title. Appearance: Yellow powder Melting point: 142-143 ° C The following compounds were produced in the same manner as in Reference Example 862.

Table 118 Table 119 Table 120 Table 121 15 twenty Table 122 Table 123 Table 124 Reference Example 909 Production of (4-benzylpiperazin-1-yl). { - [Retyl (5-nitropyridin-2-yl) amino] phenyl} methanone To a solution of 4- [methyl- (5-nitropyridin-2-yl) amino] benzoic acid (0.800 g, 2.93 mmol) and 1-benzylpiperazine (0.542 g, 3.08 mmol) in DMF (15 mL) were added triethylamine (1.02 mL, 7.32 mmol) and diethyl cyanophosphonate (0.593 mL, 3.52 mmol), and the resulting solution was stirred for 3 hours. Water was added to the resulting reaction solution and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (ethyl acetate), thereby producing 1.25 g of the compound of the title. Appearance: Amorphous yellow powder XU RNM (CDC13) d 2.25-2.65 (4H, m), 3.49 (2H, brs), 3.56 (2H, s), 3.57 (3H, s), 3.81 (2H, brs), 6.43 ( 1H, d, J = 9.5 Hz), 7.25-7.35 (7H, m), 7.53 (2H, d, J = 8.4 Hz), 8.06 (1H, dd, J = 2.8 Hz, 9.5 Hz), 9.12 (1H, d, J = 2.8 Hz). The following compounds were produced in the same manner as in Reference Example 909. Table 125 Reference Example 913 Production of N- [4- (5-nitropyridin-2-yloxy) phenyl] -N- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] acetamide To a solution of. { acetyl [4- (5-nitropyridin-2-yloxy) phenyl] amino} Ethyl acetate (2.30 g, 6.40 mraol) in ethanol (50 mL) was added 5 M aqueous sodium hydroxide (1.92 mL, 9.60 mmol), and the resulting solution was stirred at room temperature for 30 minutes. To this reaction solution were added 5 M hydrochloric acid (2 mL) and water, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, it was evaporated, and the obtained residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 1), in order to produce 1.68 g of an oil. To a solution of this oil in DMF (10 mL) were added 1-piperonylpiperazine (1.29 g, 5.86 mmol), triethylamine (1.85 mL, 13.3 mmol) and diethyl cyanophosphonate (1.07 mL, 6.36 mmol), and the resulting solution was added. stirred for 1 hour at room temperature. Water was added to this reaction solution and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, evaporated, and the residue was purified by column chromatography on silica gel. (dichloromethane: methanol = 30: 1), in order to produce 2. 21 g of the title compound. Appearance: Amorphous yellow powder XU RNM (CDC13) d 1.98 (3H, s), 2.40-2.50 (H, m), 3.40-3.45 (4H, m), 3.62 (2H, brs), 4.48 (2H, s), 5.94 (2H, s), 6.70-6.76 (2H, m), 6.85 (1H, s), 7.09 (1H, d, J = 9.1 Hz), 7.20 (2H, d, J = 8.7 Hz), 7.51 (2H , d, J = 8.7 Hz), 8.51 (1H, dd, J = 2.8 Hz, 9.1 Hz), 9.04 (1H, d, J = 2.8 Hz). The following compounds were produced in the same manner as in Reference Example 913.

Table 126 Reference Example 916 Production of 3- [3-methoxy-4- (5-nitropyridin-2-yloxy) phenyl] -1- (4-piperoniIpiperazin-1-yl) propan-1-one 3- [3-methoxy acid -4- (5-Nitropyridin-2-yloxy) phenyl] propionic acid (3.18 g, 10 mmol) was dissolved in dichloromethane (30 mL). To the resulting solution were added thionyl chloride (0.88 mL, 12 mmol) and DMF (1 drop), and refluxed for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in dichloromethane (20 mL). To the resulting solution were added triethylamine (1.67 mL, 12 mraol) and a solution of 1-piperonylpiperazine (2.20 g, 10 mmol) in dichloromethane (30 mL) under ice-cooling, and the resulting solution was stirred for 1 hour at 0 ° C. The resulting reaction solution was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from ethyl acetate, to thereby yield 4.95 g of the title compound. Appearance: Pale yellow powder RNM (CDC13) d 2.33-2.42 (4H, m), 2.63-2.69 (2H, m), 2. 97-3.03 (2H, m), 3.42 (4H, brs), 3.62-3.66 (2H, m), 3.74 (3H, s), 5.95 (2H, s), 6.73-6.75 (2H, m), 6.85- 6.90 (3H, m), 7.04 (1H, d, J = 9.1 Hz), 7.06 (1H, d, J = 7.9 Hz), 8.45 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.01 (1H, d, J = 2.8 Hz). The following compound was produced in the same manner as in Reference Example 916.

Reference Example 917 6-Chloro-N- (4-trifluoromethylphenyl) nicotinamide XH NMR (DMSO-d6) d 7.74 (1H, d, J = 8.4 Hz), 7.76 (2H, d, J = 8.7 Hz), 8.00 ( 2H, d, J = 8.7 Hz), 8.38 (1H, dd, J = 8.7 Hz, 2.5 Hz), 8.97 (1H, d, J = 2.5 Hz), 10.80 (1H, brs).

Reference Example 918 Production of 3-. { 3-Raetoxy-4- [methyl (5-nitropyridin-2-yl) amino] phenyl} -l- (4-piperoniIpiperazin-1-yl) propan-1-one To a solution of 3-. { Ethyl 3-methoxy-4- [methyl- (5-nitropyridin-2-yl) amino] phenyl Jpropionate (3.85 g, 11 mmol) in ethanol (80 mL) was added 2N aqueous sodium hydroxide (6.4 mL, 13 mmol), and the resulting solution was stirred at Arabian temperature for 2.5 hours. To the resulting reaction solution was added 6N hydrochloric acid (2.2 mL, 13 mmol), and the solvent was removed under reduced pressure. THF (80 mL) and N, N '-carbonyldiimidazole (2.08 g, 13 mmol) were added to the residue, and the resulting solution was stirred at room temperature for 3 hours. To the resulting reaction solution, 1-piperonylpiperazine (2.60 g, 12 ramol) and DMF (40 mL) were added, and the mixture was stirred at an arabiente temperature for 21 hours. The solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (ethyl acetate), with which produce 4.59 g of the title compound. Appearance: Yellow powder XU RNM (CDC13) d 2.36-2.43 (4H, m), 2.64-2.70 (2H, m), 2.99-3.05 (2H, m), 3.42-3.46 (H, m), 3.63-3.67 ( 2H, m), 3.77 (3H, s), 5.95 (2H, s), 6.12 (1H, brd, J = 9.1 Hz), 6.70-6.77 (2H, m), 6.85-6.90 (3H, m), 7.12 (1H, d, J = 8.1 Hz), 7.97-8.01 (HH, m), 9.11 (HH, d, J = 2.6 Hz).

Reference Example 919 Production of 5-. { methyl [2-oxo-2- (4-piperoniIpiperazin-1-yl) ethyl] amino} -2- (5-Nitropyridin-2-yloxy) -benzonitrile To a solution of 2- ((3-cyano-4- (5-nitropyridin-2-yloxy) phenyl) (methyl) amino) t-butyl acetate (1.2 g, 3.1 mraol) in dichloromethane (12 mL) was added trifluoroacetic acid (12 mL), and the resulting reaction solution was stirred at room temperature for 5 hours. The solvent was evaporated, and water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, to thereby produce 2- ((3-cyano-4- (5-nitropyridin-2-yloxy) phenyl) (methyl) amino) -acetic raw. To a solution of this compound in DMF (24 mL) were added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (659 mg, 3.4 mmol), 1-hydroxybenzotriazole monohydrate (526 mg, 3.4 mmol) and 1-piperonylpiperazine. (757 mg, 3.4 mmol), and the resulting reaction solution was stirred for 8 hours at room temperature. Water was added to the reaction solution and extracted with ethyl acetate. The ethyl acetate layer was then washed with, in order, saturated aqueous sodium bicarbonate solution, water and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by gel chromatography of silica (ethyl acetate), to thereby produce 412 g of the title compound. Appearance: Amorphous yellow powder XU RNM (CDCI3) d 2.40-2.55 (4H, m), 3.09 (3H, s), 3.45-3.50 (4H, m), 3.55-3.70 (2H, m), 4.14 (2H, s) ), 5.95 (2H, s), 6.70-6.80 (2H, m), 6.80-6.95 (3H, m), 7.10-7.20 (2H, m), 8.50 (1H, dd, J = 9.1 Hz, 2.8 Hz) , 8.99 (1H, d, J = 2.8 Hz).

Reference Example 920 Production of 2-. { (2,3-difluoro-4-t-butoxycarbonyl-amino) phenoxy} -5-Nitropyridine To an acid solution. { 2, 3-difluoro-4- (5-nitropyridin-2-yloxy) J-benzoic acid (1.22 g, 4.1 mmol) in t-butanol (50 mL) were added diphenylphosphoryl azide (0.98 mL, 4.5 mmol) and triethylamine (0.63 mL, 4.5 mmol). ), and the resulting solution was refluxed for 4 hours under a nitrogen atmosphere. After cooling, water was added to the reaction solution and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 6: 1), to thereby produce 1.2 g of the title compound. Appearance: White Powder XU RNM (CDCI3) d 1.54 (9H, s), 6.59-6.78 (ÍH, ra), 6.90- 75 7. 04 (1H, m), 7.13 (1H, d, J = 9.0 Hz), 7.84-8.02 (ÍH, m), 8.51 (1H, dd, J = 2.8 Hz, 9.0 Hz), 8.99 (1H, d, J = 2.8 Hz).

Reference Example 921 Production of 3,4-dichloro-N- [3-fluoro-4- (4-forraylphenoxy) phenyl] benzamide 3,4-Dichloro-N- [4- (4- [1,3] dioxsolan- 2-ylphenoxy) -3-fluorophenyl] benzamide (17.4 g, 38.9 mmol) was added to 80% acetic acid, and the resulting solution was stirred for 1.5 hours at 80 ° C. The reaction solution was concentrated under reduced pressure, where the obtained residue was recrystallized from 80% ethanol to yield 12.8 g of the title compound. Appearance: Pale yellow powder XU RNM (DMSO-d6) d 7.13 (2H, d, J = 8.6 Hz), 3.40 (1H, t, J = 9.0 Hz), 7.63 (1H, d, J = 9.0 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.90-8.00 (4H, m), 8.22 (1H, d, J = 1.9 Hz), 9.93 (1H, s), 10.67 (ÍH, s).

Reference Example 922 Production of N- [6- (4-aminophenoxy) pyridin-3-yl] -3,4-dicyrobenzamide dihydrochloride. { - [5- (3,4-dichlorobenzoylamino) pyridin-2-yloxy] phenyl} t-butyl carbamate (4.31 g, 9.09 mmol) was dissolved in a mixed solution of chloroform-methanol-ethyl acetate.

The resulting solution was concentrated to a volume of approximately 20 mL. To the residue solution was added a solution of 4 N hydrogen chloride in ethyl acetate (70 mL), and allowed to cool for 2 hours at room temperature. The precipitated white powder was filtered, and washed with ethyl acetate, thereby yielding 4.04 g of the title compound. Appearance: XU white powder RNM (DMSO-d6) d 5.20 (2H, brs), 7.14 (ΔI, d, J = 8.5 Hz), 7.25 (2H, d, J = 8.9 Hz), 7.42 (2H, d, J = 8.9 Hz), 7.84 (1H, d, J = 8.5 Hz), 7.97 (1H, dd, J = 8.5 Hz, 2.0 Hz), 8.24 (1H, dd, J = 8.5 Hz, 2.6 Hz), 8.25 (1H , d, J = 2.0 Hz), 8.5K1H, d, J = 2.6 Hz), 10.65 (1H, s). The following compounds were produced in the same manner as in Reference Example 922.

Table 127 Reference Example 926 Production of 4- (tetrahydropyran-2-yloxy) benzylaraine To a solution of lithium aluminum hydride (2.66 g, 70 mmol) in THF (200 mL) was added dropwise under cooling with ice a solution of - (tetrahydropyran-2-yloxy) benzonitrile in THF (70 mL). The resulting solution is refluxed for 1 hour. The resulting reaction solution was cooled again with ice, and then to the solution was added dropwise, in order, water (2.66 [mu] L), 1 N aqueous sodium hydroxide (2.66 [mu] L) and water (7.98 mL). The insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure, after which the residue was purified by column chromatography on silica gel (chloroform: methanol = 7: 1), to thereby yield 11.41 g of the title compound. Appearance: Colorless oil RNM (CDC13) d 1.56 (2H, s), 1. 5-1.78 (3H, m), 1.78-2.12 (3H, m), 3.53-3.66 (ÍH, m), 3.80 (2H, s) ), 3.84-3.99 (ÍH, ra), 5.4K1H, t, J = 3.2 Hz), 7.02 (2H, d, J = 8.7 Hz), 7.22 (2H, d, J = 8.7 Hz).

Reference Example 927 Production of 4- (2-fluoro-4-nitrophenoxy) phenylamine hydrochloride N- [4- (2-Fluoro-4-nitrophenoxy) phenyl] -acetamide (1.00 g, 3.45 mmol) was added to hydrochloric acid 6 M (10 mL) and the resulting solution was refluxed for 2 hours. The resulting reaction solution was concentrated under reduced pressure, to thereby produce 0.910 g of the title compound. Appearance: Pale yellow powder XU RNM (DMSO-d6) d 3.40-4.00 (2H, m), 7.18 (1H, t, J = 8.7 Hz), 7.24 (2H, d, J = 8.9 Hz), 7.32 (2H, d, J = 8.9 Hz), 8.10 (1H, ddd, J = 1.4 Hz, 2.6 Hz, 8.9 Hz), 8.35 (1H, dd, J = 2.6 Hz, 10.8 Hz).

Reference Example 928 Ester production. { 4- [5- (3,4-dichlorobenzoylaraine) pyridin-2-yloxy] phenyl} Phenyl Carbamate To a suspension of N- [6- (4-amino-phenoxy) pyridin-3-yl] -3-dichlorobenzamide dihydrochloride (700 mg, 1.57 mmol) in THF (20 mL) was added triethylamine (1.1 mL, 7.89 mmol). To the resulting solution was then added dropwise phenyl chlorocarbonate (0.39 mL, 3.14 mmol) under cooling with ice. The resulting reaction solution was stirred for 1 hour at room temperature. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, whereby the residue solidified into a powder. The powder was filtered, and washed with diethyl ether, to thereby produce 470 mg of the title compound. Appearance: White powder XU RNM (DMSO-de) d 7.04 (1H, d, J = 8.9 Hz), 7.11 (2H, d, J = 8.9 Hz), 7.19-7.31 (3H, m), 7.38-7.49 (2H, m), 7.53 (2H, d, J = 8.0 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.95 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.18 (1H, dd, J = 8.9 Hz, 2.2 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.47 (1H, d, J = 2.2 Hz), 10.26 (1H, s), 10.54 (1H, s). The following compounds were produced in the same manner as in Reference Example 928.

Table 128 Reference Example 932 Production of 4-piperonylpiperazine-l-carboxylic acid [4- (2-fluoro-4-nitrophenoxy) phenyl] amide To a solution of ester [4- (2-fluoro-4-nitrophenoxy) -phenyl] carbamate of phenyl (0.700 g, 1.90 mmol) in DMF (15 mL) was added 1-piperonylpiperazine (0.460 g, 2.09 mmol), and the resulting solution was stirred for 2 hours at room temperature. Water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine. The ethyl acetate layer was dried over anhydrous sodium sulfate, and evaporated, to thereby yield 0.939 g of the title compound. Appearance: Yellow oil XU RNM (DMSO-d6) d 2.30-2.40 (4H, m), 3.35-3.50 (6H, m), 6.00 (2H, s), 6.70-6.90 (2H, m), 7.00-7.15 ( 2H, m), 7.55 (2H, d, J = 9.1 Hz), 8.05-8.10 (HH, m), 8.30 (1H, dd, J = 2.8 Hz, 10.9 Hz), 9.31 (HH, s). The following compounds were produced in the same manner as in Reference Example 932.

Reference Example 933 ethyl 3- (4-. {5- [3- (3, 4-Dichlorophenyl) -3-ethylureido] -pyridin-2-yloxy} phenyl) propionate MS 501 (M +).

Table 129 Reference Example 936 Production of 4-piperonylpiperazine-l-carboxylic acid 4-hydroxybenzylamide To a solution of 4-piperonylpiperazine-l-carboxylic acid 4- (tetrahydropyran-2-yloxy) benzylamide (1.1 g, 2.43 mmol) in methanol (50%). mL) was added p-toluenesulfonic acid monohydrate (1.0 g, 5.26 mraol), and the resulting solution it was stirred for 1 hour at room temperature. The resulting reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, thereby yielding 330 mg of the title compound. Appearance: Powder white XU RNM (CDC13) d 2.41 (4H, t, J = 5.0 Hz), 3.37 (4H, t, J = 5.0 Hz), 3.42 (2H, s), 4.32 (2H, d, J = 5.2 Hz), 4.68 (1H, t, J = 5.2 Hz), 5.94 (2H, s), 6.15 (1H, brs), 6.70-6.80 (2H, m), 6. 75 (2H, d, J = 8.6 Hz), 6.84 (1H, s), 7.13 (2H, d, J = 8.6 Hz). The following compound was produced in the same manner as in Reference Example 936.

Reference Example 937 4-Benzylpiperazine-1-carboxylic acid hydrochloride (4-hydroxyphenyl) methylamide XU NMR (DMSO-de) d 2.69-2.91 (2H, ra), 3.03 (3H, s), 2. 92-3.23 (4H, m), 3.68 (2H, d, J = 13.7 Hz), 4.26 (2H, s), 6.75 (2H, d, J = 8.7 Hz), 6.98 (2H, d, J = 8.7 Hz ), 7.45 (3H, brs), 7.54 (2H, brs), 9.52 (1H, s).

Reference Example 938 Production of 3,4-dichloro-N-. { 6- [4- (3-hydroxypropyl) -phenoxy] pyridin-3-yl} benzamide A 2-. { 4- [3- (t-butyldimethylsilanyloxy) propyl] -phenoxy} -5-Nitropyridine (950 mg, 1.8 mmol) were added acetic acid (10 mL) and water (5 mL), and the resulting solution was stirred for 1 hour at room temperature. The resulting reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from ethyl acetate, to thereby yield 520 mg of the title compound. Appearance: White prisms XU RNM (DMSO-d6) d 1.70-1.78 (2H, m), 2.59-2.65 (2H, ra), 3.32-3.47 (2H, m), 4.46-4.49 (ÍH, m), 7.00- 7.05 (3H, m), 7.23 (2H, d, J = 8.2 Hz), 7.84 (1H, d, J = 8.2 Hz), 7.95 (1H, dd, J = 8.3 Hz, 2.0 Hz), 8.16-8.22 ( 2H, m), 8.48 (1H, d, J = 2.6 Hz), 10.54 (1H, s). The following compound was produced in the same manner as in Reference Example 938.

Reference Example 939 3, -Dichloro-N-. { 6- [4- (2-hydroxyethyl) phenoxy] pyridin-3-yl} benzamide NMR (DMSO-de) d 2.73 (2H, t, J = 6.9 Hz), 3.59-3.66 (2H, m), 4.65 (1H, t, J = 5.3 Hz), 7.00-7.06 (3H, m), 7. 25 (2H, d, J = 8.3 Hz), 7.84 (1H, d, J = 8.3 Hz), 7.95 (1H, dd, J = 8.3 Hz, 2.0 Hz), 8.16-8.23 (2H, ra), 8.47 (1H, d, J = 2.6 Hz), 10.54 (ÍH, s).

Reference Example 940 Production of 3,4-dichloro-N-. { 6- [4- (5-hydroxypentyl) -phenoxy] pyridin-3-yl} benzamide to a solution of 5-. { 4- [5- (3, 4-dichloro-benzoylamino) pyridin-2-yloxy] phenyl ethylpentanoate (8.79 g, 18.0 mmol) in THF (140 mL) was added sodium borohydride (3.14 g, 144 mmol), and the resulting solution was refluxed for 3 hours under a nitrogen atmosphere. The resulting reaction solution was cooled with ice, and treated with 1 N hydrochloric acid. The resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 2), in order to produce 7. 07 g of the title compound. Appearance: White Powder XU RNM (CDC13) d 1.25-1.75 (7H, m), 2.62 (2H, t, J = 7.6 Hz), 3.65 (2H, t, J = 6.6 Hz), 6.92 (1H, d, J = 8.5 Hz), 7.02 (2H, d, J = 8.5 Hz), 7.19 (2H, d, J = 8.5 Hz), 7.56 (1H, d, J = 8.5 Hz), 7.69 (1H, dd, J = 8.5 Hz, 2.0 Hz), 7.93 (1H, s), 7.97 (1H, d, J = 2.0 Hz), 8.15 (1H, dd, J = 8.5 Hz, 2.5 Hz), 8.22 (ÍH, d, J = 2.5 Hz ). The following compounds were produced in the same manner as in Reference Example 940.

Table 130 Table 131 Reference Example 948 Production of 4-cyano-N- [6- (4-hydroxymethylphenoxy) pyridin-3-yl] benzamide A suspension of 4- [5- (4-cyanobenzoylamino)] pyridin-2-yloxy] benzoic acid (1.80 g, 5.01 mmol) in THF (20 [mu] L) was cooled with common salt-ice, and to the solution was added triethylamine (0.77 mL, 5.51 mmol), and then ethyl chloroformate (0.53 mmol). mL, 5.51 mmol). The resulting solution was stirred at room temperature. Thirty minutes later, the reaction solution was filtered and the insoluble matter was removed. The resulting filtrate was poured while stirring under cooling with ice in an aqueous solution of sodium borohydride (0.95 g, 25.05 mmol) in 80% methanol (40 mL). After stirring for 30 minutes at room temperature, water (200 mL) was added to the reaction solution. The obtained mixture was extracted with ethyl acetate (200 mL). The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The residue was recrystallized from a mixed solution of ethyl acetate-n-hexane, to thereby yield 1.26 g of the title compound. Appearance: Dust slightly yellow XU RNM (DMSO-de) d 4.50 (2H, d, J = 5.3 Hz), 5.19 (1H, t, J = 5.6 Hz), 7.04 - 7.09 (3H, m), 7.35 (2H, d, J = 8.6 Hz), 8.04 (2H, d, J = 8.9 Hz), 8.12 (2H, d, J = 8.6 Hz), 8.21 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.49 (1H , d, J = 2.3 Hz), 11.63 (ÍH, s).

The following compounds were produced in the same manner as in Reference Example 948.

Reference Example 949 4-Chloro-N- [6- (4-hydroxylamethylphenoxy) pyridin-3-yl] benzamide XU NMR (DMSO-de) d 4.50 (2H, d, J = 5.3 Hz), 5.18 (1H, t , J = 5.6 Hz), 7.03-7.08 (3H, m), 7.35 (2H, d, J = 8.6 Hz), 7.63 (2H, d, J = 8.6 Hz), 8.00 (2H, d, J = 8.6 Hz ), 8.20 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.48 (1H, d, J = 2.3 Hz), 10.46 (1H, s).

Table 132 398 Reference Example 955 Production of 2- [4- (1-broraoethyl) phenoxy] -5-nitropyridine 2- (4-ethylphenoxy) -5-nitropyridine (7.33 g, 30 mraol) was dissolved in carbon tetrachloride (100 mL) , and N-bromosuccimide (5.34 g, 30 mmol) and benzoyl peroxide (0.73 g, 3 mmol) were added to the resulting solution. This solution was refluxed overnight under a nitrogen atmosphere. The reaction solution was allowed to cool, after which the insoluble matter was removed by filtration. The resulting filtrate was washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 10: 1), thereby producing 1.34 g of the title compound. Appearance: White powder RNM (CDC13) d 2.08 (3H, d, J = 6.9 Hz), 5.26 (1H, q, J = 6.9 Hz), 7.05 (1H, d, J = 9.1 Hz), 7.15 (2H, d , J = 8.6 Hz), 7.53 (2H, d, J = 8.7 Hz), 8.49 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.0 (ÍH, d, J = 2.8 Hz).

Reference Example 956 Production of N- [6- (4-chloromethylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide To a solution of N- [6- (4-hydroxymethylphenoxy) -pyridin-3-yl] -4- trifluoromethylbenzamide (3.06 g, 7.9 mmol) in dichloromethane (90 mL) was added thionyl chloride (1.7 mL, 23.3 mmol), and the resulting solution was stirred for 4 hours at room temperature. A solution of saturated sodium bicarbonate was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was washed with diethyl ether, to thereby yield 2.95 g of the title compound. Appearance: White powder V H NMR (CDCI3) d 4.61 (2H, s), 7.00 (1H, d, J = 8.9 Hz), 7.11-7.1 (2H, m), 7. 1-7.4 (2H, m), 7.77 (2H, d , J = 8.4 Hz), 7.89 (1H, brs), 8.00 (2H, d, J = 8.4 Hz), 8.22-8.28 (2H, m). The following compounds were produced in the same manner as in Reference Example 956.

Reference Example 957 3, 4-Dichloro-N- [4- (4-chloromethylphenoxy) -3-fluorophenyl] benzamide I NMR (CDCI3) d 4.58 (2H, s), 6.95 (2H, d, J = 8.6 Hz), 7.10 (1H, t, J = 8.6 Hz), 7.20-7.30 (ÍH, m), 7.30-7. 0 (3H, m), 7.59 (1H, d, J = 8.3 Hz), 7.65-7.78 (2H, ra), 7.96 (1H, d, J = 2.1 Hz).

Table 133 (CNPh means a cyanophenyl group, henceforth in the present CNPh it indicates the same meaning) Reference Example 963 Production of 3,4-dichloro-N- hydrochloride. { 6- [4- (5-Chloropentyl) -phenoxy] pyridin-3-yl} benzamide A 3, 4-dichloro-N-. { 6- [4- (5-hydroxypentyl) -phenoxy] pyridin-3-ylbenzamide (6.83 g, 15.34 mmol) was added thionyl chloride (35 mL). The resulting solution was stirred for 20 minutes at room temperature, followed by stirring for 1 hour at 50 ° C. The excess thionyl chloride was evaporated, after which ethyl acetate (100 mL) was added to the resulting residue. The white powder obtained was filtered, and washed with ethyl acetate, to which yield 6.98 g of the title compound. Appearance: White Powder XU RNM (DMSO-d6) d 1.33-1.50 (2H, m), 1.50-1.68 (2H, m), 1.68-1.85 (2H, m), 2.59 (2H, t, J = 7.6 Hz) , 3.64 (2H, t, J = 6.6 Hz), 7.02 (2H, d, J = 8.5 Hz), 7.03 (1H, d, J = 9.0 Hz), 7. 23 (2H, d, J = 8.5 Hz), 7.83 (1H, d, J = 8.5 Hz), 7.97 (1H, dd, J = 8.5 Hz, 2.0 Hz), 8.20 (1H, dd, J = 9.0 Hz, 2.5 Hz), 8. 25 (1H, d, J = 2.0 Hz), 8.50 (1H, d, J = 2.5 Hz), 10.63 (1H, s). The following compounds were produced in the same manner as in Reference Example 963.

Table 134 Reference Example 968 Production of N-. { 6- [4- (2-Broraoacetyl) phenoxy] pyridin-3-yl} -3,4-dichlorobenzaraide N- [6- (4-acetylphenoxy) pyridin-3-yl} -3,4-dichlorobenzamide (4.0 g, 10 mmol) was dissolved in chloroform (200 mL). Copper bromide was added to the resulting solution (5.76 g, 25 mmol), and refluxed overnight. The resulting reaction solution was filtered, and the filtrate was washed with sodium thiosulfate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. Ethyl acetate was added, and it was washed with saturated sodium thiosulfate, water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residues were combined during the purification by column chromatography on silica gel (n-hexane: ethyl acetate = 3: 1), thereby producing 1.86 g of the title compound. Appearance: XU white powder RNM (CDC13) d 4.43 (2H, s), 7.06 (1H, d, J = 8.7 Hz), 7.21 (2H, d, J = 8.9 Hz), 7.57 (1H, d, J = 8.4 Hz), 7.72 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.99 (1H, d, J = 2.0 Hz), 8.03 (2H, d, J = 8.9 Hz), 8.09 (1H, brs), 8.27 (1H, dd, J = 8.7 Hz, 2.8 Hz), 8.32 (1H, d, J = 2.2 Hz). The following compound was produced in the same manner as in Reference Example 968.

Reference Example 969 N-. { 4- [4- (2-Bromoacetyl) phenoxy] -3-fluorophenyl} -3,4-dichlorobenzamide XU NMR (DMSO-D6) d 4.88 (2H, s), 7.06 (2H, d, J = 8.9 Hz), 7.30-7.50 (lH, m), 7.60-7.70 (HI, ra), 7.80-8.20 (5H, ra), 8.22 (1H, d, J = 2.0 Hz), 10.67 (1H, brs).

Reference Example 970 Production of A '- [4- (3-broraopropil) phenoxy] -3, 4-dichloro-3' -fluorobenzanilida To a suspension of 3-dichloro-3 '-fluoro-4' - [4- (3-hydroxypropyl) phenoxy] benzanilide (2.32 g, 5.34 mmol) in dichloromethane (46 mL) were added carbon tetrabromide (2.13 g, 6.41 mmol) and triphenylphosphine (1.54 g, 5.88 mmol), and the resulting solution was stirred for 12 hours at room temperature. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 5: 1), to thereby yield 2.41 g of the title compound.

Appearance: White powder XH RNM (CDC13) d 2.08-2.11 (2H, m), 2.73 (2H, t, J = 7. 3 Hz), 3.38 (2H, t, J = 6.5 Hz), 6.88 (2H, d, J = 8.5 Hz), 7. 02 (1H, dd, J = 9.0 Hz, 8.0 Hz), 7.13 (2H, d, J = 8.5 Hz), 7.17-7.28 (HI, ra), 7.54 (1H, d, J = 8.3 Hz), 7.60- 7.74 (2H, m), 7. 85 (1H, brs), 7.93 (1H, d, J = 2.0 Hz). The following co-treatments were produced in the same manner as in Reference Example 970.

Table 135 Reference Example 973 Production of 4- [4- (5-nitropyridin-2-yloxy) benzyl] piperazine-1-carboxylic acid t-butyl To a solution of 2- (4-clorometilf enoxy) -5-nitropyridine (12.32 g , 47 mmol) in DMF (120 mL) were added triethylamine (19.4 mL, 140 mmol) and piperazine-1-t-butylcarboxylate (11.27 g, 61 mmol), and the resulting solution was stirred for 3 hours at 50 ° C. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 1), thereby producing 11.26 g of the title compound. Appearance: Yellow powder XU RNM (CDC13) d 1.46 (9H, s), 2.40 - 2. 4 (4 H, m), 3.43-3.46 (4H, m), 3.54 (2H, s), 7.04 (1H, d) , J = 8.9 Hz), 7.09-7.14 (2H, m), 7.38 -7.44 (2H, m), 8.48 (1H, dd, J = 8.9 Hz, 2.8 Hz), 9.05 (1 H, d, J = 2.8 Hz). The following compound was produced in the same manner as in Reference Example 973.

Reference Example 974 4-. { 1- [4- (5-Nitropyridin-2-yloxy) phenyl] ethyl} XU morpholine NMR (CDCl3) d 1.38 (3H, d, J = 6.8 Hz), 2.36-2.54 (4H, m), 3.37 (1H, q, J = 6.8 Hz), 3.69-3.72 (4H, m), 7.02 (1H, dd, J = 9.1 Hz, 0.5 Hz), 7.11 (2H, d, J = 8.6 Hz), 7.40 (2H, d, J = 8.5 Hz), 8.47 (1H, dd, J = 9.1 Hz, 2.8 Hz), 9.06 (1H, dd, J = 2.8 Hz, 0.5 Hz).

Reference Example 975 Production of N 6- (4-nitrophenoxy) pyridin-3-ylmethyl methanesulfonic acid [6- (4-nitrophenoxy) pyridin-3-yl] methanol (6.1 g, 24.8 mmol) was dissolved in dichloromethane (150 mL), and to the resulting solution was added triethylamine (4.15 mL, 29.8 mmol) under cooling with ice. To the resulting solution was added dropwise methanesulfonic acid chloride (2.11 mL, 27.3 mmol), and then stirred under a nitrogen atmosphere for 30 minutes at 0 ° C. The reaction solution was washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. A mixed solvent (50 mL) of n-hexane: ethyl acetate = 1: 1 was added to the residue. The crystals were removed by suction filtration, to thereby produce 7.9 g of the title compound. Appearance: White Powder XU RNM (CDC13) d 3.04 (3H, s), 5.23 (2H, s), 7.09 (1H, d, J = 8.4 Hz), 7.29 (2H, d, J = 9.1 Hz), 7.88 ( 1H, dd, J = 8.4 Hz, 2.5 Hz), 8.23 (1H, d, J = 2.3 Hz), 8.28 (2H, d ^ J = 9.1 Hz). The following compounds were produced in the same manner as in Reference Example 975.

Table 136 Reference Example 978 Production of 2- (4-nitrophenoxy) -5- (4-trifluoromethyl-phenoxymethyl) pyridine 6- (4-Nitrophenoxy) -pyridin-3-ylmethyl methanesulfonic acid ester (4.86 g, 15 mmol) was dissolved in DMF (250 mL), and 4-hydroxybenzotrifluoride (2.92 g, 18 mraol) and potassium carbonate (3.11 g, 22.5 mmol) were added to the resulting solution.

The resulting solution was stirred under a nitrogen atmosphere for 1 hour at 50 ° C. The reaction solution was concentrated under reduced pressure. Ethyl acetate was added to the residue, and it was washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 80: 1), in order to produce . 8 g of the title compound. Appearance: Pale yellow powder RNM (CDC13) d 5.09 (2H, s), 7.02-7.10 (3H, m), 7.26-7.31 (2H, m), 7.56-7.59 (2H, m), 7.88 (1H, dd, J = 8.4 Hz, 2.5 Hz), 8.25-8.31 (3H, m). The following compound was produced in the same manner as in Reference Example 978.

Reference Example 979 2- (2-Methyl-4-nitrophenoxy) -5- (4-trifluoromethyl-phenoxymethyl) pyridine RNM (CDCl 3) d 2.31 (3H, s), 5.07 (2H, s), 7.03 (2H, d , J = 8.6 Hz), 7.08 (1H, d, J = 8.4 Hz), 7.17 (1H, d, J = 8.9 Hz), 7.57 (2H, d, J = 8.4 Hz), 7.87 (1H, dd, J = 8.4 Hz, 2.5 Hz), 8.10 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.18 (1H, d, J = 2.6 Hz), 8.21 (ÍH, d, J = 2.5 Hz).

Example 1 Production of N-. { 6- [4- (4-benzylpiperazine-1-carbonyl) -phenoxy] pyridin-3-yl} -4-trifluoroacetylbenzaraide To a solution of 4- [5- (4-trifluoromethyl-benzoylamino) pyridin-2-yloxy] benzoic acid (1.19 g, 2.3 mmol) in DMF (30 mL) were added l-ethyl-3- hydrochloride (3-dimethylaminopropyl) carbodiimide (530 mg, 2.8 mmol), monohydrate 1-hydroxybenzotriazole (370 mg, 2.7 mmol) and benzylpiperazine (0.475 mL, 2.7 mmol) under ice-cooling. The resulting solution was stirred for 1 day by gradually warming to room temperature. A solution of saturated sodium bicarbonate was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (methanol: chloroform = 1: 19), thereby producing 800 mg of the title compound. Appearance: White XU needles RNM (CDC13) d 2.46 (4H, brs), 3.55 (2H, s), 3.72 (4H, brs), 6.96 (1H, d, J = 8.9 Hz), 7.10-7.13 (2H, m ), 7.28-7.40 (7H, m), 7.74 (2H, d, J = 8.3 Hz), 8.02 (2H, d, J = 8.3 Hz), 8.16-8.21 (1H, m), 8.32 (1H, d, J = 2.6 Hz), 8.53 (1H, brs). The following compounds were produced in the same as in Example 1.

Table 137 Table 138 Table 139 Table 140 Table 141 Table 142 Table 143 Table 144 Table 145 Table 146 Table 147 Table 148 Table 149 Table 150 Table 151 Table 152 Table 153 Table 154 Table 155 Table 156 Table 157 Table 158 Table 159 16 Table 160 Table 161 Table 162 Table 163 C Table 164 Table 165 Table 166 Table 167 Table 168 Table 169 Table 170 Table 171 Table 172 Table 173 Table 174 Table 175 Table 176 Table 177 Table 178 Table 179 Table 180 Table 181 Table 182 Table 183 Table 185 Table 186 Table 187 Table 188 Table 189 Table 190 Table 191 Table 192 (TsOH means a p-toluenesulfonic acid, hereinafter in the present TsOH indicates the same meaning) Table 193 In the table mentioned above, Ya? means a group of and Ya2 means a group of 85 Table 194 Table 195 Table 196 Table 197 Table 198 Table 199 Table 200 Table 201 Table 202 Table 203 Table 204 Table 205 Table 206 Table 207 78 Table 208 Table 209 Table 210 Table 211 Table 212 Table 213 Table 214 Table 215 Table 216 Table 217 Table 218 Table 219 Table 220 Table 221 Table 222 Table 223 Table 224 Table 225 The following compounds were made in the same manner as in Reference Example 918.

Table 226 Table 227 Table 228 Table 229 Table 230 Table 231 Example 950 Production of 3,4-dichloro-N-. { 6- [4- (4-phenethii piperazine-1-carbonyl) phenoxy] pyridin-3-yl} Benzamide To a solution of ethyl 4- (5-aminopyridin-2-yloxy) benzoate (690 mg, 2.7 mmol) in THF (10 mL) were added triethylamine (0.73 mL, 5.3 mmol) and 3,4-dichlorobenzoyl chloride (570 mg, 2.7 mmol) under cooling with ice, and the resulting solution was stirred for 1 hour under cooling with ice. This reaction solution was concentrated under reduced pressure, and ethyl acetate was added to the residue. The resulting solution was washed with water, 1N hydrochloric acid and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was washed, when hot, with n-hexane: dichloromethane = 1: 2. The product was dissolved in THF (20 mL). 1N aqueous sodium hydroxide was added to the residue (2.9 mL, 2.9 mmol), and this solution was stirred for 5 hours at 100 ° C. THF was evaporated, and the aqueous layer was made to have a pH of 3 with 1 N hydrochloric acid. The precipitated material was collected by filtration, and dried. The resulting product was dissolved in DMF (10 mL), and 1-phenet and 1-piperazine (200 mg, 1.1 mmol), l-ethyl-3- (3-dimet i laminopr opi 1) carbodiimide hydrochloride (240 mg, 1.3 mmol) and 1-hydroxybenzotriazol monohydrate (170 mg, 1.3 mmol) were added to the solution. The resulting solution was stirred for 1 day at room temperature. This reaction solution was concentrated under reduced pressure, and chloroform was added to the residue. The resulting solution was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (methanol: chloroform = 1: 99), to thereby yield 310 mg of the title compound. Appearance: White powder XH NMR (CDC13) d 2.54 (4H, brs), 2.62-2.68 (2H, m), 2.79-2.85 (2H, m), 3.60-3.73 (4H, m), 6.95 (1H, d, J = 8.9 Hz), 7.09-7.23 (5H, m), 7.27-7.33 (2H, m), 7.37-7.41 (2H, m), 7.55 (1H, d, J = 8.3 Hz), 7.74-7.78 (HI) , m), 8.04 (1H, d, J = 2.0 Hz), 8. 11-8.15 (1H, m), 8.31 (1H, d, J = 2.6 Hz), 8.57 (1H, brs). The following compounds were produced in the same manner as in Example 950.

Table 232 Table 233 Table 234 Table 235 Example 1036 Production of 2-. { 3-methy1-4- [5- (4-trifluoromethylbenzoyl) pyridin-2-yloxy] phenylamino} -1- (4-piperonylopiperazin-1-yl) ethanone To a solution of 2-chloro-5- (4-trifluoromethylbenzoyl) pyridine (1.00 g, 3.5 mmol) in DMF (30 mL) were added ethyl N- ester ( -hydroxy-3-methylphenyl) glycine (0.81 g, 3.9 mmol), cesium carbonate (1.71 g, 5.2 mmol) and copper iodide (I) (200 mg, 1.05 mmol), and the resulting solution was stirred for 3.5 hours at 60 ° C under an argon atmosphere. The resulting reaction solution was filtered and concentrated. Water was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 3: 1), thereby producing 1.20 g of a yellow oil. The yellow oil was dissolved in THF (23 mL), and 1 M aqueous sodium hydroxide (3.9 mL, 3.9 mmol) was added to the solution. The resulting solution was stirred for 3 hours at room temperature. This reaction solution was cooled with ice, and made to have a pH of 1 with 6 M hydrochloric acid. The resulting solution was extracted with ethyl acetate, and the ethyl acetate layer was washed with water and then dried over magnesium sulfate anhydrous. He The solvent was evaporated under reduced pressure, thereby producing 1.04 g of a yellow oil. This yellow oil was dissolved in DMF (20 mL), and 1-piperonylpiperazine (530 mg, 2.4 mmol), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride was added to the resulting solution. (560 mg, 2.9 mmol) and 1-hydroxybenzotriazole monohydrate (390 mg, 2.6 mmol), and the resulting solution was stirred for 15 hours at room temperature. The reaction solution was concentrated under reduced pressure, and water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 2 - »acetate of ethyl), in order to produce 280 mg of a yellow oil. To this oil diethyl ether was added and allowed to stand. The precipitated material was collected by filtration, in order to produce 220 mg of the title compound. Appearance: Yellow powder RNM (CDC13) d 2.11 (3H, s), 2.43-2.48 (4H, m), 3.45- 3.48 (4H, m), 3.67-3.71 (2H, m), 3.86 (2H, d, J = 4.1 Hz), 4.90 (1H, t, J = 4.1 Hz), 5.96 (2H, s), 6.49-6.53 (2H, m), 6.71-6.78 (2H, m), 6.86-6.97 (3H, m) , 7.75 (2H, d, J = 8.1 Hz), 7.87 (2H, d, J = 8.1 Hz), 8.18 (1H, dd, J = 8.7 Hz, 2.5 Hz), 8.58 (IH, d, J = 2.1 Hz ).

The following compound was produced in the same manner as in Example 1036.

Example 1037 6- (4-. {[2- (-Pyperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2,5-difluorofenoxi) -N- (4-t rif luoromethyl) phenyl) nor cot inamide Melting point: 224.5 - 226.0 ° C Example 1038 Production of N- (6-. {2-met i 1-4- [methyl- (2-oxo-2-piperazin-1-ylethyl) amino] phenoxy] pyridin-3-yl) -3 , 4-dichlorobenzamide To a solution of methyl acid. { 4- [5- (3,4-dichlorobenzoylamino) -pyridin-2-yloxy] -3-methylphenyl enyl} aminoacetic (1.59 g, 3.5 mmol) in DMF (60 mL) were added l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.79 g, 4.1 mmol), 1-hydroxybenzotriazole monohydrate (0.63 g, 4.1 mmol) , and 1-t-butyloxycarbonylpiperazine (0.68 g, 3.6 mmol). The resulting solution was stirred for 15 hours at room temperature under a nitrogen atmosphere. Water was added to the solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and then the ethyl acetate layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n- hexane: ethyl acetate = 2: 1 - »3: 2), thereby producing an amide product. This amide product was dissolved in THF (20 mL). 10% hydrochloric acid (10 mL) was then added to the solution, and the resulting solution was stirred for 14 hours at room temperature. To this reaction solution was added a solution of saturated sodium bicarbonate to make the neutral solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by column chromatography on silica gel (dichloromethane: methanol = 50: 1 -> 20: 1), thereby producing 0.38 g of the title compound. Appearance: Colorless amorphous powder RNM (CDC13) d 2.10 (3H, s), 2.75-2.94 (4H, m), 2.99 (3H, s), 3.40-3.70 (4H, m), 4.08 (2H, s), 6.46 -6.59 (2H, m), 6.79 (1H, d, J = 8.9 Hz), 6.89 (1H, d, J = 8.6 Hz), 7.55 (1H, d, J = 8.4 Hz), 7.71 (1H, dd, J = 8.4 Hz, 2.1 Hz), 7.98 (1H, d, J = 2.1 Hz), 8.03-8.14 (2H, m), 8.23 (1H, d, J = 2.6 Hz).

Example 1039 Production of N- (6- { 4- [3- (4-piperonylopiperazin-1-yl) -3-oxopropyl] phenoxy] pyridin-3-yl) -4-trifluoromethyl benzamide To a solution of 3- [4- (5-aminopyridin-2-yloxy) phenyl] -1- (4-piperonylopiperazin-1-yl) propan-1-one trichlorohydrate (200 mg, 0.35 mmol) in THF (4 mL) were added triethylamine (0.243 mL, 1.8 mmol) and 4-trifluoromethylbenzoyl chloride (0.055 mL, 0.37 mmol), and the resulting solution was stirred for 1 hour at room temperature. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was recrystallized from diethyl ether, to thereby yield 170 mg of the title compound. Appearance: White powder Melting point: 140-141 ° CH RNM (CDC13) d 2.32-2.40 (4H, m), 2.59-2.65 (2H, m), 2.93-2.99 (2H, m), 3.41 (4H, brs ), 3.60-3.64 (2H, m), 5.94 (2H, s), 6.71-6.77 (2H, m), 6.85 (1H, s), 6.96 (1H, d, J = 8.9 Hz), 7.05 (2H, d, J = 8.4 Hz), 7.22 (2H, d, J = 8.4 Hz), 7.76 (2H, d, J = 8.4 Hz), 8.01 (2H, d, J = 8.4 Hz), 8.11-8.14 (ÍH, m), 8.23 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.28 (1H, d, J = 2.7 Hz). A crude titled product (77.4 g) obtained using the same procedures was recrystallized from ethyl acetate (400 mL), to thereby yield 49.66 g of the title compound. Appearance: White powder; Melting point: 142-144 ° C The following compounds were produced in the same manner as in Example 1039.

Table 236 Table 237 1 Table 238 Table 239 Table 240 Table 241 Table 242 Table 243 Table 244 Table 245 Table 246 Table 247 Table 248 Table 249 Table 250 Table 251 Table 252 Table 253 1. 15 (3H, t, J = 6..9 Hz), 1.26-1.39 (3H, m), 1.99 (ÍH, brs),. 2.13 (1H, brs), 2.63-2.67 (1H, m), 2.79-2.83 (lH, m), 3.00-4.67 (9H, m), 5.95 (2H, s), 6.61 (2H, d, J = 8 ..4 Hz), 6.74 (2H, 1163 4-CF, Ph- -CH, brs), 6.82 (ÍH, d, J = 8.7 Hz), 6.87 (1H, brs), 6.95 (2H, d, J = 8.9 Hz), 7.7K2H, d, J = 7.9 Hz), 7.99 (2H, d, J = 8.1 Hz), 8.10 (1H, d, J = 8.3 Hz), 8.27 (ÍH, d, J = 2.5 Hz), 38 (ÍH, brs).

Table 254 Table 255 Table 256 Table 257 Table 258 Table 259 Table 260 Table 261 Table 262 Table 263 Table 264 Table 265 Example 1217 Production of. { 6- [4- (2, -dioxothiazolidin-5-ylmethyl) -2-methylphenoxy] pyridin-3-yl} lH-indole-2-carboxylic acid amide To a solution of 5 - [4 - (5-aminopyr idin-2 -i-loxi) -3-methyl-t-benzyl] t ia zol idin-2, 4 -dione (150 mg, 0.46 mmol) in DMF (5 mL) were added indole-2-carboxylic acid (74 mg, 0.46 mmol), 1-hydroxybenzo triazol monohydrate (70 mg, 0.46 mmol) and hydrochloride 1-ethyl-1 -3- (3-dimethylaminopropyl) carbodiimide (110 mg, 0.57 mmol), and the resulting solution was stirred for 5 days at room temperature. This reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, evaporated, and the residue was then purified by column chromatography on silica gel (chloroform: methanol = 30: 1). Ethanol was added to the obtained powder solution, the resulting solution was filtered and the filtrate was washed with ethanol, thereby producing 100 mg of the title compound. Appearance: White Powder XU RNM (DMSO-d6) d 2.10 (3H, s), 3.09 (1H, dd, J = 14.2 Hz, 9.7 Hz), 3.40 (1H, dd, J = 14.2 Hz, 4.2 Hz), 4.94 (1H, dd, J = 9.7 Hz, 4.2 Hz), 6.99 (1H, d, J = 8.2 Hz), 7.04 (1H, d, J = 8.9 Hz), 7.05- 7.16 (2 H, m), 7.20 ( 1H, s), 7.24 (1H, dd, J = 7.0 Hz, 1.0 Hz), 7.39 (1H, d, J = 1.6 Hz), 7.46 (1H, d, J = 8.2 Hz), 7.68 (1H, d, J = 7.7 Hz), 8.21 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.49 (1H, d, J = 2.8 Hz), 10.37 (1H, s), 11.80 (1H, s), 12.09 (H) , s). The following compounds were produced in the same manner as in Example 1217.

Table 266 Table 267 Table 268 Table 269 Table 270 Table 271 Table 272 Table 273 Table 274 Table 275 Table 276 Table 277 Table 278 Table 279 Table 280 Table 281 Table 282 Table 283 Table 284 Table 285 Example 1503 Production of N- [6- (4-. {[2- (4-piperonylopiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4- trifluoromethylbenzamide To a suspension of 1- (4-piperoni lopiper az in-1-yl) -2-. { methyl- [3-methyl-4- (5-nitropyridin-2-yloxy) f eni 1] amino} ethanone (2.65 g, 5.10 mmol) in ethyl acetate (50 mL) was added 5% platinum-carbon (0.20 g) under a nitrogen atmosphere, and the resulting mixture was stirred for 11 hours under an atmosphere of hydrogen. The platinum-carbon was removed by filtration using Celite. To a solution of Resulting filtrate in ethyl acetate was added triethylamine (0.78 mL, 5.61 mmol) under cooling with ice, and then to the resulting solution was added 4- (tri-fluoromethyl) benzoyl chloride (0.80 mL, 5.36 mmol). This reaction solution was stirred for 16 hours, and then a solution of saturated sodium bicarbonate was added thereto. The resulting solution was stirred at room temperature, and after 20 minutes, extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was recrystallized from acetone-diethyl ether, to thereby yield 3.03 g of the title compound. Appearance: Pale yellow powder. Melting point: 153.0 - 15.5 ° C; XH NMR (CDC13) d 2.12 (3H, s), 2.31-2.52 (4H, m), 3.01 (3H, s), 3.38-3.72 (6H, m), 4.07 (2H, s), 5.95 (2H, s) ), 6. 9 - 6.61 (2 H, m), 6.69-6.78 (2H, m), 6.79-6.88 (2H, m), 6.92 (1 H, d, J = 8.6 Hz), 7.76 (2H, d , J = 8.3 Hz), 7.81 -7.90 (HH, m), 7.99 (2H, d, J = 8.3 Hz), 8.13 (1H, dd, J = 8.8 Hz, 2.6 Hz), 8.23 (HH, d, J = 2.6 Hz). A crude titled product (5.00 g, 7.6 mmol) obtained using the same procedures is recrystallized from ethanol (15 mL), thereby yielding 3.90 g of the title compound. Appearance: Pale yellow powder Melting point: 156-158 ° C The following compounds were produced in the same manner as in Example 1503. Example 1504 N-. { 6- [2-met? L-4- (2-oxo-3-p? Peron? Lo? M? Dazol? D? N-l-l) f enoxi] p? R? Dm-3-? L} -4-tr? F 1 uo r orne tilben amide pf 188.0 - 189.0 ° C Table 286 Table 287 Table 288 Table 289 0 * Table 290 Table 291 Table 292 Example 1615 Production of 3,4-dichloro-N- [6- (2-fluoro-4-. {Methyl] [2-oxo-2- (4-piperonylopiperazin-1-yl) ethyl] amino] phenoxy) pyridin-3-yl] benzenesulfonamide To a solution of 2-. { [4- (5-aminopyridin-2-yloxy) -3-fluorophenyl] methylamino} -1- (4-piperonylopiperazin-1-yl) ethanone (15.85 g, 1.9 mmol) in dichloromethane (150 mL) were added 3,4-dichlorobenzenesulfonyl chloride (12.92 g, 1.9 mmol) and pyridine (11 mL, 12.4 mmol), and the resulting solution was stirred for 1 hour at room temperature. Water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (ethyl acetate), and recrystallized from ethanol, to thereby yield 5.6 g of the title compound. Appearance: White powder; Melting point: 185.6-187.0 ° C; And RNM (CDC13) d 2.45 (4H, t, J = 4.6 Hz), 3.01 (3H, s), 3.44 (2H, s), 3.47 (2H, brs), 3.64 (2H, brs), 4.07 (2H, s), 5.95 (2H, s), 6.33-6.44 (2H, m), 6.71-6.78 (2H, m), 6.84-6.87 (2H, m), 6.98 (1H, t, J = 9.1 Hz), 7.47 (1H, dd, J = 8.4 Hz, 2.0 Hz), 7.51 (2H, dd, J = 8.4 Hz, 2.8 Hz), 7.68 (1H, d, J = 2.1 Hz), 7.83 (1H, d, J = 1.8) Hz); MS 701 (M +).

The following compounds were produced in the same manner as in Example 1615.

Table 294 Table 295 Table 296 Table 297 Table 298 Table 299 Table 300 Table 301 Table 302 101 Table 303 Table 304 Table 305 Table 306 Table 307 Table 308 101 Table 309 [019 Table 310 Table 311 1 Table 312 942 Table 313 1 Table 314 Table 315 Table 316 Table 317 Table 318 Table 319 '954 Table 320 Table 321 Table 322 Example 2031 N-. { 4- [4- (4-Benzenesulfonylpiperazin-1-yl) phenoxy] phenyl} -3,4-dichlorobenzamide Melting point: 191-192 ° C The following compounds were produced in the same manner as in Reference Example 292.

Table 323 Example 2034 Production of 4-. { 4- [5- (3,4-dichlorobenzoyl-amino) pyridin-2-yloxy] phenylcarbamoyl} piperidin-1-t-butyl carboxylate To a solution of N- [6- (4-aminophenoxy) pyridin-3-yl] -3,4-dichlorobenzamide dihydrochloride (1.0 g, 2.24 mmol) in DMF (15 mL) they added, mono-t-butyl ester of piperidine-1,4-dicarboxylic acid (510 mg, 2.22 mmol), triethylamine (0.94 mL, 6.74 mmol), 1-hydroxybenzotriazole monohydrate (350 mg, 2.29 mmol) and hydrochloride of 1 -ethyl-3- (3-dimethylaminopropyl) carbodiimide (514 mg, 2.68 mmol) 1 7 under cooling with ice. The resulting solution was then stirred under ice-cooling for 1 hour, and at room temperature for 17 hours. This reaction solution was concentrated under reduced pressure. The residue was diluted with water and ethyl acetate, whereupon a white powder was precipitated. The white powder was filtered, then washed with water, and subsequently washed with ethyl acetate, to thereby yield 1.04 g of the title compound. Appearance: White powder RNM (DMSO-d6) d 1.41 (9H, s), 1.35-1.50 (2H, m), 1. 70-1.85 (2H, m), 2.40-2.60 (HH, m), 2.65-2.90 (2H, m), 3.90-4.11 (2H, m), 7.03 (1H, d, J = 8.9 Hz), 7.06 ( 2H, d, J = 8.9 Hz), 7.62 (2H, d, J = 8.9 Hz), 7.84 (1H, d, J = 8.5 Hz), 7.94 (1H, dd, J = 8.5 Hz, 2.0 Hz), 8.17 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.46 (1H, d, J = 2.6 Hz), 9.96 (1H, s), 10.54 (1H, s ). The following compound was produced in the same manner as in Example 2034.

Example 2035 3,4-Dichloro-N- (6-. {4- [2- (2,4-dioxothiazolidin-5-yl) -acetylamino] phenoxy] pyridin-3-yl) benzamide XH NMR (DMSO -de) d 3.07 (ÍH, dd, J = 16.5 Hz, 8.9 Hz), 3. 24 (1H, dd, J = 16.5 Hz, 4.0 Hz), 4.73 (1H, dd, J = 9.0 Hz, 4.0 Hz), 7.04 (1H, d, J = 8.9 Hz), 7.08 (2H, d, J = 8.9 Hz), 7. 58 (2H, d, J = 8.9 Hz), 7.84 (1H, d, J = 8.2 Hz), 7.94 (1H, dd, J = 8.2 Hz, 2.0 Hz), 8.18 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.46 (1H, d, J = 2.6 Hz), 10.21 (1H, s), 10.53 (HH, s), 12.00 (HH, s).

EXAMPLE 2036 Production of 3,4-dichloro-N- (6-. {4- [4-piperonyl-piperazin-1-ylmethyl] phenoxy] pyridin-3-yl) benzamide To a solution of 3-4 dichloro-N- [6- (4-piperazin-1-ylmethylphenoxy) pyridin-3-yl] benzamide (300 mg, 0.66 mmol) in DMF (10 mL) were added piperonylic acid (120 mg, 0.72 mmol), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (140 mg, 0.73 mmol) and 1-hydroxybenzotriazole monohydrate (100 mg, 0.74 mmol ) under cooling with ice. The resulting reaction solution was stirred overnight at room temperature. A solution of saturated sodium bicarbonate was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated, in order to produce 110 mg of the title compound. Appearance: White powder XH NMR (CDC13) d 2.46 (4H, brs), 3.53 (2H, s), 3.60 (4H, brs), 5.99 (2H, s), 6.79 (1H, d, J = 7.9 Hz), 6.85-6.96 (3H, m), 7. 08 (2H, d, J = 8.6 Hz), 7.33 (2H, d, J = 8.3 Hz), 7.54 (1H, d, J = 8.3 Hz), 7.69-7.73 (ÍH, m), 7.99 (1H, d , J = 2.3 Hz), 8.16-8.21 (1H, m), 8.27-8.30 (2H, m). The following co-treatments were produced in the same manner as in Example 2036.

Table 324 Table 325 Table 326 Example 2056 Production of N-. { 6- [4- (4-Chloroacetylpiperazino) phenoxy] -3-pyridyl} -4- (trifluoromethyl) benzamide To a solution of N- [6- (4-piperazinofenoxi) -3-pyridyl] -4- (tri-fluorome ti-1) benzamide (885 mg, 2.00 mmol) in DMF (20 mL) were added triethylamine (0.418 mL, 3.00 mmol) and chloroacetyl chloride (0.191 g, 2. 40 mmol), and the resulting reaction solution was stirred for 10 minutes at room temperature. To this reaction solution was added ethyl acetate. The resulting solution was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, thereby producing 1.00 g of the title compound. Appearance: XU white powder RNM (CDC13) d 3.17 (2H, t, J = 5.0 Hz), 3.22 (2H, t, J = 5.0 Hz), 3.70 (2H, t, J = 5.0 Hz), 3.80 (2H, t, J = 5.0 Hz), 6.95 (1H, d, J = 9.0 Hz), 6.97 (2H, d, J = 9.0 Hz), 7.08 (2H, d, J = 9.0 Hz), 7.77 (1H, brs) , 7.78 (2H, d, J = 8.0 Hz), 7.99 (2H, d, J = 8.0 Hz), 8.20 (1H, dd, J = 9.0 Hz, 2.5 Hz), 8.26 (1H, d, J = 2.5 Hz ). The following compounds were produced in the same manner as in Example 2056.

Table 327 Table 328 Table 329 Table 330 Table 331 Table 332 Table 333 Example 2095 Production of 1-. { 4- [4- (3, 4-dichlorobenzoylamino) -phenoxy] phenyl} -4-benzoyloxy-piperidine To a solution of 1-. { - [4- (3,4-dichlorobenzoylamino) phenoxy] phenyl} -4-hydroxypiperidine (200 mg, 0.44 mraol) in dichloromethane (8 mL) was added with triethylamine (0.091 mL, 0.65 mmol), benzoyl chloride (74 mg, 0.53 mmol) and 4- (dimethylamino) pyridine (3 mg , 0.025 mmol), and the resulting solution was stirred for 2.5 days at room temperature. This reaction solution was purified by chromatography on colurane on silica gel (methanol: dichloromethane = 7: 93), thereby producing 80 mg of the title compound.

Appearance: White powder Melting point: 188-190 ° C Example 2096 Production of 3,4-dichloro-N- (6- { 4- [[2-oxo-2- (4-piperonylpiperazin-1-yl) ethyl] (2,2,2-trifluoroacetyl) araino] phenoxy, pyridin-3-yl) benzamide To a solution of 3,4-dichloro-N- (6- (4- [2-oxo-2- (4-piperonylpiperazin-1-yl) ethylamino] phenoxy]. pyridin-3-yl) benzamide (0.152 g, 0.239 mmol) in THF (5 mL) were added triethylamine (0.0500 mL, 0.359 mmol) and trifluoroacetic anhydride (0.0410 mL, 0.287 mmol), and the resulting solution was stirred for 6 hours Water was added to the resulting reaction solution, and extracted with ethyl acetate.The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated.The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 20: 1) to produce a solid.This solid was recrystallized from methanol, thereby yielding 28.8 mg of the title compound Appearance: White powder Melting point: 211- twenty-one 3 ° C The following compound was produced in the same manner as in Example 2096.

EXAMPLE 2097 N- [6- (Acetyl [2-oxo-2- (4-piperonylpiperazin-1-yl) ethyl] araino} -2-raetoxyphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide Yl NMR (CDC13) d 1.90 (3H, s), 2.28 (2H, brs), 2. 38 (2H, brs), 3.37 (4H, brs), 3.49 (2H, brs), 3.67 (3H, s), 4.43 (2H, s), 5.93 (2H, s), 6.68-6.75 (2H, m) , 6.82 (1H, s), 6.91-ß.97 (2H, m), 7.07-7.10 (2H, m), 7.53 (1H, d, J = 8.4 Hz), 7.76 (1H, dd, J = 8.4 Hz , 2.0 Hz), 8.05 (1H, d, J = 2.0 Hz), 8.20 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.37 (1H, d, J = 2.6 Hz), 9.26 (ÍH, s) .

Example 2098 Production of N- [6- (benzoyl) {4- [3-oxo-3- (4-piperoniylpiperiin-1-yl) propyl] phenyl} araino) pyridin-3-yl monooxalate -3,4-dichlorobenzaraide To a solution of 3,4-dichloro-N- (6-. {4 - [3-oxo-3- (4-piperonylpiperazin-1-yl) propyl] phenylamino} -pyridin -3-yl) benzamide (250 mg, 0.395 mmol) in THF (5 L) was added triethylamine (0.132 mL, 0.949 mmol) and benzoyl chloride (0.0550 mL, 0.474 mmol), and the resulting solution was stirred for 7 hours. hours at room temperature. Water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 10: 1) to yield 0.300 g of a free form. To this free form was added isopropanol (5 mL) and oxalic acid dihydrate (100 mg, 0.793 mmol), and the resulting solution was dissolved under heat. The solvent was evaporated, and the resulting solid was recrystallized from isopropanol, thereby yielding 80.0 mg of the title compound. Appearance: Yellow powder Melting point: 140-143 ° C The following compound was produced in the same manner as in Example 2098.

Example 2099 N- [6- (Acetyl (4- [3-oxo-3- (4-piperonylpiperazin-1-yl) propyl] phenyl} araino) pyridin-3-yl] -3,4-dichlorobenzamide fusion: 150-165 ° C XU RNM (DMSO-d6) d 1.98 (3H, s), 2.62-2.98 (7H, ra), 3.04 (1H, t, J = 12.1 Hz), 3.26 (2H, t, J = 14.7 Hz), 3.35-3.50 (2H, m), 4.06 (1H, d, J = 13.8 Hz), 4.13-4.26 (2H, m), 4.44 (1H, d, J = 13.8 Hz), 6.07 (2H , s), 6.95-7.02 (2H, m), 7.20 -7.24 (3H, m), 7.28 (2H, d, J = 8.3 Hz), 7.52 (1H, d, J = 8.9 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.96 (1H, dd, J = 2.0 Hz, 8.4 Hz), 8.23- 8. 26 (2H, m), 8.77 (1H, s), 10.77 (1H, s), 11.10 (1H, br s).

Example 2100 Production of 6-. { 4 - [3 - (4 -piperoni Ipiper a z in- 1-yl) -3-oxopropyl] phenoxy} -N- (3, 4-dichloro phenyl) nor cotamide A to a solution of 6- acid. { 4- [3- (4-piperonylpiperazin-1-yl) -3-oxopropyl] phenoxy (nicotinic acid (1.23 g, 2.5 mmol) in THF (35 mL) was added N, N'-carboni ldi imide zol (540 mg , 3.3 mmol), and the resulting solution was stirred for 30 minutes at room temperature The resulting reaction solution was concentrated under reduced pressure, and 3, -dichloroani-1a (4.07 g, 25 mmol) was added to the residue. The resulting solution was stirred for 3 days at room temperature, the solvent was evaporated under reduced pressure, the residue was purified by column chromatography on silica gel (ethyl acetate), and the resulting product was recrystallized from diethyl ether, with which yields 510 mg of the title compound Appearance: White powder XU NMR (CDC13) d 2.33 (4H, brs), 2.59-2.65 (2H, ra), 2.91 -2.97 (2H, m), 3.40 (4H, brs) , 3.59 (2H, S), 5.94 (2H, s), 6.70-6.76 (2H, m), 6.83 (1H, s), 6.96- 7. 06 (3H, ra), 7.20 -7.26 (2H, m), 7.40 (1H, d, J = 8.6 Hz), 7.50-7.54 (ÍH, m), 7.86 (1H, d, J = 1.8 Hz), 8.18 -8.22 (1H, m), 8.44 (1H, brs), 8.66 (1H, brs).

The following compounds were produced in the same manner as in Example 2100.

Table 334 Example 2106 Production of (4-benz? Lp? Perazm-l-? L). { 4- [5- (3, 4-d? Chlorophen? Lsulfan? L) p? R? D? N-2-? Lox?] Fen? L) methanone To a solution of [4- (5-am? Nop ? pd? n-2-yloxy) phenyl] (4-benz? lp? perazm-l-? l) methanone (0.73 g, 1.88 mmol) in concentrated sulfuric acid (0.38 mL) - water (1.1 mL) was added by dropping a solution of sodium nitrate (0.13 g, 1.88 mmol) in water (0.6 mL) under cooling with ice. The reaction mixture was stirred for 10 minutes. This reaction mixture was added to a solution of 3,4-dichlorobenthiol (0.24 mL, 1.88 ramol) in sodium hydroxide aqueous 2 N (2 mL) under cooling with ice. Water was added to the resulting reaction solution, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, and it evaporated. The residue was purified by chromatography on silica gel (dichloromethane: methanol = 80: 1), in order to produce 0.1 g of the title compound. Appearance: Yellow oil XH RNM (CDC13) d 2.49 (4H, brs), 3.56 (2H, s), 3.56 (2H, brs), 3.78 (2H, brs), 6.99 (1H, d, J = 8.9 Hz), 7.20 (2H, d, J = 8.7 Hz), 7.25-7.39 (5H, m), 7.46 (1H, dd, J = 8.2 Hz, 2.0 Hz), 7.47 (2H, d, J = 8.7 Hz), 7.56 ( 1H, d, J = 8.2 Hz), 7.76 (1H, d, J = 2.0 Hz), 7.86 (1H, dd, J = 8.9 Hz, 2.5 Hz), 8.50 (H, d, J = 2.5 Hz). The following compound was produced in the same manner as in Example 2106.

Example 2107 2- ( { 4- [5- (3,4-Dichlorophenylsulfanyl) pyridin-2-yloxy] -3-methoxyphenyl} ethylamino) -1- (4-piperonylpiperazin-1-yl) ethanone XH NMR (CDCl 3) d 1.20 (3H, t, J = 7.0 Hz), 2.43 (4H, t, J = 4.9 Hz), 3.43 (2H, s), 3.35-3.50 (2H, m), 3. 9-3.60 ( 2H, m), 3.60-3.70 (2H, m), 3.73 (3H, s), 4.05 (2H, s), 5.95 (2H, s), 6.22 (1H, dd, J = 8.9 Hz, 2. 7 Hz ), 6.35 (1H, d, J = 2.7 Hz), 6. 70-6.76 (2H, m), 6.85 (1H, s), 6.90 (1H, d, J = 9.0 Hz), 6.98 (1H, d, J = 8.8 Hz), 7.46 (1H, dd, J = 8.2 Hz , 2.0 Hz), 7.55 (1H, d, J = 8.2 Hz), 7.75 (1H, d, J = 2.0 Hz), 7.78 (1H, dd, J = 9.0 Hz, 2.5 Hz), 8.49 (1H, d, J = 2.5 Hz).

Example 2108 Production of 1- (6-. {- [3- (4-piperonylpiperazin-1-yl) -3-oxopropyl] phenoxy] pyridin-3-yl) -3- (3,4-dichlorophenyl) urea To a solution of 3- [4- (5-aminopyridin-2-yloxy) phenyl] -1- (4-piperonylpiperazin-1-yl) propane-1-one (600 mg, 1.3 mmol) in toluene (20 mL ) was added ethyldiisopropylamine (0.454 mL, 2.6 mmol) and 3,4-dichlorophenylisocyanate (270 mg, 1.4 mraol), and the resulting solution was stirred for 1 day under reflux. The reaction solution was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (methanol: chloroform = 1: 19), and then recrystallized from ethyl acetate to thereby yield 280 mg of the title compound. Appearance: Pale yellow powder? U RNM (CDC13) d 2.37-2.39 (4H, m), 2.61-2.67 (2H, m), 2.89-2.94 (2H, m), 3.41-3.47 (4H, m), 3.61- 3.65 (2H, m), 5.94 (2H, s), 6.69-6.83 (4H, m), 6.95 (2H, d, J = 8.4 Hz), 7.10-7.26 (4H, m), 7.49 (1H, d, J = 2.3 Hz-), 7.93-7.96 (2H, ra), 8.15 (1H, s), 8.21 (ÍH, s).

The following compounds were produced in the same manner as in Example 2108. Table 335 Example 2113 Production of 4- [5- (3,4-dichlorobenzoylamino) pyridin-2-yloxy] phenyl hydrochloride} 4-piperoniIpiperazine-1-carboxylic acid amide To a solution of (4- [5- (3,4-dichlorobenzoyl-amino) pyridin-2-yloxy] phenyl] -carbamic acid phenyl ester (320 mg, 0.65 mmol) in DMF (4 mL) was added 1-piperoni Ipiperazine (285 mg, 1.29 mmol), and the resulting solution was stirred for 17 hours at room temperature.This reaction solution was concentrated under reduced pressure. added water to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by column chromatography on silica gel (dichloromethane: methanol = 25: 1). The obtained residue was dissolved in a mixed solvent of ethanol-ethyl acetate. To the resulting solution was added a solution of 4 N hydrogen chloride in ethyl acetate to bring the pH to 3. The precipitated white powder was then filtered and washed with ethanol, thereby yielding 330 mg of the title compound . Appearance: White powder XH NMR (DMSO-d6) d 2.85 - 3.09 (2 H, m), 3.20- 3.50 (4H, m), 4.12 - .38 (4 H, m), 6.08 (2H, s), 7.02 (2H, d, J = 9.0 Hz), 6.93-7.12 (3H, m), 7.28 (1H, d, J = 1.5 Hz), 7.49 (2H, d, J = 9.0 Hz), 7.83 (1H, d, J = 8.5 Hz), 7.97 (1H, dd, J = 8.5 Hz, 2.0 Hz), 8.19 (1H, dd, J = 8.8 Hz, 2.6 Hz), 8.25 (1H, d, J = 2.0 Hz), 8.50 ( 1H, d, J = 2.6 Hz), 8.92 (1H, s), 10.63 (1H, s).

The following compound was produced in the same manner as in Example 2113.

Example 2114 (4- [5- (3, 4-Dichlorobenzoylamino) pyridin-2-yloxy] phenyl} -hydrochloride 4-benzylpiperazine-1-carboxylic acid amide RNM (DMS0-d6) d 2.90-3.20 (2H, m), 3.22-3.45 (4H, m), 4.27 (2H, d, J = 13.6 Hz), 4.35 (2H, d, J = 5.0 Hz), 7.02 (1H, d, J = 8.9 Hz), 7.03 ( 2H, d, J = 8.9 Hz), 7.41-7.52 (3H, m), 7.48 (2H, d, J = 8.9 Hz), 7.55-7.69 (2H, m), 7.84 (1H, d, J = 8.4 Hz ), 7.97 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.19 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.25 (1H, d, J = 2.0 Hz), 8.49 (1H, d, J = 2.6 Hz), 8.90 (1H, s), 10.62 (1H, s).

Example 2115 Production of 2- [(4- {5- [(3,4-dichlorobenzylidene) -araino] pyridin-2-yloxy} phenyl) methylamino] -1- (4-piperonylpiperazin-1-yl) ethanone 2-. { [(4- (5-aminopyridin-2-yloxy) phenyl] methylamino] -1- (4-piperonylpiperazin-1-yl) ethanone (7.80 g, 16.4 mmol) was dissolved in methanol (400 mL), and to the resulting solution was added 3,4-dichlorobenzaldehyde (2.87 g, 16.4 mmol). This solution was refluxed for 16 hours. The resulting reaction solution was concentrated under reduced pressure, to thereby yield 10.4 g of the title compound. Appearance: Coffee XH RNM (CDC13) d 2.44 (4H, brs), 3.03 (3H, s), 3.44- 3. 45 (2H, m), 3.50 (2H, brs), 3.63 (2H, brs), 4.09 (2H, s), 5.94 (2H, s), 6.65-6.77 (4H, m), 6.84-6.88 (2H, m), 7.03 (2H, d, J = 9.1 Hz), 7.54 (1H, d, J = 8.3 Hz), 7.58 (1H, dd, J = 8.9 Hz, 2.8 Hz), 7.70 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.00 (1H, d, J = 2.0 Hz), 8.10 (1H, d, J = 2.8 Hz), 8.39 (1H, s). The following compounds were produced in the same manner as in Example 2115.

Table 336 Table 337 Table 338 Table 339 Example 2133 Production of 3- ( { - [5- (3, -dichlorobenzyloamino) -pyridin-2-yloxy] phenyl}. Methylamino) -1- (4-piperonylpiperazin-1-yl) propan-1-one 3- [(4- {5- (3,4-dichlorobenzylidene) pyridin-2-yloxy} phenyl) methylamino] -1- (4-piperonylpiperazin-1-yl) propan-1-one (3.88 g , 6.0 mmol) was dissolved in a mixed solvent of methanol (150 mL) and THF (50 mL). To the resulting solution was slowly added sodium borohydride (1.13 q, 30.0 mmol) and this resulting solution was stirred for 13 hours at room temperature. This reaction solution was concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate, and washed with a bicarbonate solution of saturated sodium and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by chromatography on colurane on silica gel (dichloromethane: methanol = 40: 1), thereby producing 3.60 g of the title compound. Appearance: xti white powder RNM (CDC13) d 2.32-2.39 (4H, m), 2.52-2.57 (2H, m), 2.91 (3H, s), 3.36-3.40 (4H, ra), 3.59-3.63 (2H, m), 3.66-3.71 (2H, m), 3.97 (1H, brs), 4.27 (2H, d, J = 5.0 Hz), 5.94 (2H, s), 6.65-6.76 (5H, m), 6.83 (1H , d, J = 1.0 Hz), 6.94 (1H, dd, J = 8.9 Hz, 3.0 Hz), 6.97 (2H, d, J = 9.2 Hz), 7.18 (1H, dd, J = 8.3 Hz, 2.0 Hz) , 7.40 (1H, d, J = 8.4 Hz), 7.45 (1H, d, J = 2.0 Hz), 7.56 (1H, d, J = 2.5 Hz); MS 647 (M +). The following compounds were produced in the same manner as in Example 2133.

Table 340 Table 341 Table 342 Table 343 Example 2150 Production of 1- (4-benzylpiperazin-1-yl) -3- (A -. {5- (piperonylamino) pyridin-2-yloxy} phenyl) propan-1-one 3- [4- ( 5-aminopyridin-2-yloxy) phenyl] -1- (4-piperonylpiperazin-1-yl) propan-1-one (1.04 g, 2.5 mmol) was dissolved in methanol (25 mL). To the resulting solution was added piperonal (0.39 g, 2.63 mmol), and this solution was refluxed overnight. The resulting reaction solution was cooled with ice, and then sodium borohydride (0.28 g, 7.50 mmol) was added. The resulting solution was stirred for 2 hours at room temperature. This reaction solution was concentrated under reduced pressure. The residue was diluted with ethyl acetate, and washed with water, saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by column chromatography on silica gel (ethyl acetate), to thereby produce 0.80 g of the title compound.

Appearance: Yellow RNM oil (DMSO-d6) d 2.28 (4H, brs), 2.57 (2H, t, J = 7.9 Hz), 2.76 (2H, t, J = 7.9 Hz), 3. 0-3.46 (6H, m), 4.15 (2H, d, J = 6.1 Hz), 5.97 (2H, s), 6.21 (1H, t, J = 6.1 Hz), 6.76 (1H, d, J = 8.6 Hz), 6.82-6.86 ( 4H, m), 6.92 (1H, brs), 7.08 (1H, dd, J = 8.7 Hz, 3.0 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.24-7.32 (5H, m), 7.51 ( ÍH, d, J = 3.0 Hz). The following compounds were produced in the same manner as in Example 2150.

Table 344 Table 345 Table 346 Example 2171 Production of 1- (4-benzylpiperazin-1-yl) -3- [4- (5-dibenzyloarainopyridin-2-yloxy) phenyl] propan-l-one 3- [4- (5-aminopyridin-2-yloxy ) phenyl] -1- (4-benzyl piperazin-1-yl) propan-1-one (1.0 g, 2.4 mmol) was dissolved in DMF (30 mL). To this solution were added potassium carbonate (0.73 g, 5.28 mmol), sodium iodide (0.76 g, 5.04 mmol) and benzyl bromide (0.60 raL, 5.04 mraol), and the solution The resulting mixture was stirred at room temperature overnight. This reaction solution was concentrated under reduced pressure. The residue was diluted with chloroform, and washed with water, saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by column chromatography on silica gel (chloroform: methanol = 80: 1), to thereby yield 0.67 g of the title compound. Appearance: Yellow oil? NMR (DMSO-d6) d 2.27 (4H, brs), 2.50-2.59 (2H, ra), 2.73-2.78 (2H, m), 3.37-3.45 (6H, m), 4.68 (4H, s), 6.78 ( 1H, d, J = 8.9 Hz), 6.85 (2H, d, J = 8.4 Hz), 7.17 (2H, d, J = 8.6 Hz), 7.20-7.36 (16H, m), 7.54 (1H, d, J = 3.1 Hz).

Example 2172 Production of 2 - [(4- {5 - [(3,4-dichlorobenzyl) -ethylamino] pyridin-2-yloxy} phenyl) methylamino] -1- (4-piperonylpiperazin-1-yl) ethanone 2- ( { 4- [5- (3,4-dichlorobenzyloamino) pyridin-2-yloxy] phenyl} methylamino) -1- (4-piperonylpiperazin-1-yl) ethanone (1.59 g, 2.5 mmol ) was dissolved in dichloroethane (80 mL). To this solution were added acetoaldehyde (1.40 mL, 25.0 mmol) and sodium triacetyloxy borohydride (1.59 mL, 7.5 mmol) under ice-cooling. The resulting solution is acetic acid (0.43 mL, 7.5 mmol) was added dropwise, and this solution was stirred at room temperature for 16 hours. The resulting reaction solution was washed with a saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by column chromatography on silica gel (chloroform: methanol = 50: 1). The solid obtained was recrystallized from ethanol, thereby producing 0.65 g of the title compound. Appearance: White powder? Ti RNM (CDC13) d 1.17 (3H, t, J = 7.1 Hz), 2.41 (4H, brs), 2.99 (3H, s), 3.36-3.44 (4H, m), 3.48 (2H, brs), 3.62 (2H, brs), 4.04 (2H, s), 4.35 (2H, s), 5.95 (2H, s), 6.67-6.77 (5H, m), 6.85 (1H, brs), 6.97 (2H , d, J = 9.1 Hz), 7.01 (1H, dd, J = 8.9 Hz, 3.1 Hz), 7.07 (1H, dd, J = 3.2 Hz, 2.0 Hz), 7.32 (HI, d, J = 2.0 Hz) , 7.37 (ÍH, d, J = 8.3 Hz), 7.63 (1H, d, J = 3.0 Hz); MS 661 (M +). The following compounds were produced in the same manner as in Example 2172.

Table 347 Table 348 Table 349 Table 350 Table 351 [088 Table 352 Table 353 Table 354 Table 355 Table 356 Example 2235 Production of (4- {5- [benzyl- (3,4-dichlorobenzyl) -amino] pyridin-2-yloxy} - (4-benzylpiperazin-1-yl) methanone (4-Benzylpiperazin-1-) il) (4- [5- (3,4-dichlorobenzyloamino) pyridin-2-yloxy] phenyl] methanone (1.09 g, 2. 0 mmol) was dissolved in DMF (30 mL). To this solution were added potassium carbonate (0.28 g, 2.0 mmol) and benzyl bromide (0.24 mL, 2.0 mmol), and the resulting solution was stirred at room temperature for 2 hours, then subsequently stirred for 1 hour at 70 ° C. ° C. To the resulting solution were further added potassium carbonate (0.03 g, 0.2 mmol) and benzyl bromide (0.02 mL, 0.2 mmol), and this solution was stirred for 3 hours at 70 ° C. To the resulting solution was added potassium carbonate (0.03 g, 0.2 mmol), benzyl bromide (0.02 mL, 0.2 mmol) and sodium iodide (0.15 g, 1.0 mmol), and this solution was stirred during the night at 70 ° C. The resulting reaction solution was concentrated under reduced pressure. The residue was diluted with chloroform, and this solution was washed with water, saturated sodium bicarbonate solution and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by column chromatography on silica gel (ethyl acetate), to thereby yield 0.64 g of the title compound. Appearance: Pale yellow oil? U RNM (CDC13) d 2.37 (4H, brs), 3.28-3.50 (6H, m), 4.71 (2H, s), 4.73 (2H, s), 6.90 (1H, d, J = 8.9 Hz), 6.99 (2H, d, J = 8.6 Hz), 7.22-7.37 (14H, m), 7.52 (1H, d, J = 2.0 Hz), 7.58-7.6I (2H, m).

The following compounds were produced in the same manner as in Example 2235. Table 357 Table 358 Table 359 Table 360 Table 361 Table 362 Table 363 104 Example 2270 Production of 1- (t-butoxycarbonyl) -A-. { A - [A - (3,4-dichlorobenzoylamino) phenoxy] phenyl} -4-hydroxypiperidine To a solution of N- [4- (4-bromophenoxy) phenyl] -3,4-dichlorobenzamide (4.94 g, 11.3 mmol) in THF (100 mL) was stirred at -85 ° C, and added a 2.46 M solution of n-butyl lithium hexane (9.65 mL, 23.7 mmol) by dripping for 10 minutes. When stirred for 20 minutes at the same temperature, crystals were precipitated. To this reaction solution was added a solution of 1- (t-butoxycarbonyl) -4-piperidone (2.48 g, 12.4 mmol) in THF (20 mL). The temperature of the solution was raised for 3 hours at -40 ° C, and then saturated aqueous ammonium chloride was added to the solution. The resulting reaction solution was extracted with ethyl acetate, and dried over anhydrous magnesium sulfate. The solvent was then evaporated, and the residue was purified by column chromatography on silica gel (ethyl acetate: n-hexane = 2: 3 to 1: 1), to yield 2.30 g of a white powder. These crystals were washed with ether, in order to produce 1.80 g of the title compound. Appearance: White powder Melting point: 208-209 ° C [05 EXAMPLE 2271 Production of 1- (t-butoxycarbonyl) -4- (4- {4- [4- (3, -dichlorobenzoylamino) phenoxy] phenyl} -1,2,5,6-tetrahydropyridine To one solution of 1- (t-butoxycarbonyl) -4- { 4- [4- (3,4-dichlorobenzoylamino) phenoxy] phenyl} -4-hydroxypiperidine (1.56 g, 2.80 mmol) in toluene (32 mL) was it added p-toluenesulfonic acid hydrate (53 mg, 0.28 mmol), and the resulting solution was refluxed for 18 hours.The resulting reaction solution was purified by column chromatography on silica gel (dichloromethane: methanol = 20: 1), to produce 1.35 g of the title compound Appearance: White powder Melting point: 173-174 ° C Example 2272 Production of 1-. { 4- [4- (3, 4-dichlorobenzoylamino) -phenoxy] phenyl} -4-hydroxypiperidine To a solution of 1-. { 4- [4- (3, 4-dichlorobenzoi 1-amino) phenoxy] phenyl} -A- (methoxymethoxy) piperidine (5.50 g, 11.0 mmol) in ethanol (110 mL) was added 2 M hydrochloric acid (55 mL, 110 mmol), and the resulting solution was stirred for 8 hours at 60 ° C. To the resulting reaction solution was added potassium carbonate (16 g) at room temperature, and the solvent was evaporated under reduced pressure. IT was added water (200 mL) to the residue. Precipitated crystals were collected by filtration, to thereby produce 5.0 g of the title compound. Appearance: Pale brown powder Melting point: 178-180 ° C Example 2273 Production of 1- (3- {4- [4- (3,4-dichlorobenzoylamino) -phenoxy] phenyl} propionyl) piperazine monohydrochloride To a solution of 1- (t-butoxycarbonyl) -4- (3-. {- [4- (3,4-Dichlorobenzoylamino) phenoxy] phenyl]., .propionyl) piperazine (2.40 g, 4.01 mmol) in dichloromethane (24 mL) was added trifluoroacetic acid (12 mL) under cooling with ice, and the resulting solution was stirred for 3 hours at the same temperature. The solvent was evaporated. Acetone (5 mL) was added to the residue, and then a solution of saturated sodium bicarbonate was added to make the basic solution. The formed solids were collected by filtration and dried, whereby 2.00 g of a free white powder was obtained. This free form (0.500 g) was dissolved in ethanol (10 mL) and 5 M hydrochloric acid (0.4 mL) by heating. The solvent was then evaporated, and the solid obtained was recrystallized from isopropanol, to thereby yield 0.388 g of the title compound. Appearance: White powder 107 Melting point: 127-130 ° C The following compounds were produced in the same manner as in Example 2273.

Table 364 Table 365 Table 366 Example 2291 [3- (4-. {5- [3- (3, -Dichlorophenyl) ureido] pyridin-2-yloxy] -3-methyl-phenyl) -2-oxotetrahydropyrin-idin-1-yl] acetic acid XU NMR (DMSO-d6) d 1.87-2.15 (5H, m), 3.25-3.47 (2H, m), 3.58-3.75 (2H, m), 3.95 (2H, s), 6.82-7.00 (2H, m) , 7.01-7.12 (HH, m), 7.17 (1H, d, J = 2.4 Hz), 7.29-7.32 (HH, m), 7.50 (1H, d, J = 8.8 Hz), 7. 85 (1H, d, J = 2.4 Hz), 7.89-8.02 (HH, m), 8.11 (1H, d, J = 2.7 Hz), 8.95 (1H, s), 9.17 (1H, s), 12.50 (1H , s). The following compounds were produced in the same manner as in Reference Example 922.

Table 367 Table 368 Example 2299 Production of 1 (3 { 4- [4- (3,4-dicJorobenzoylamino) -phenoxy] phenyl} propionyl) -4-piperoniIpiperazine hydrochloride To a suspension consisting of 1- (3- {4- [4- (3,4-dichlorobenzoylamino) phenoxy] phenyl}. Propionyl) -piperazine (0.500 g, 1.00 mmol) and diisopropylethylamine (0.262 raL, 1.50 mmol) in acetonitrile (12 mL) was added chloride of piperonyl (0.188 g, 1.10 mmol), and the resulting solution was heated to reflux for 1.5 hours. Water was added to this reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 30: 1), in order to produce 0.486 g of a free forrase. This free form was dissolved in ethanol (10 mL) and 5 M hydrochloric acid (0.3 mL) by heating. The solvent was then evaporated, and the solid obtained was recrystallized from 90% ethanol (17.5 mL), thereby producing 0.322 g of the title compound. Appearance: White powder Melting point: 221-224 ° C A crude titled product (9.95 g, 14.9 mmol) obtained using the same procedures was recrystallized from 80% ethanol (350 mL), thereby producing 9.37 g of the Title. Appearance: White powder Melting point: 232-234 ° C The following compounds were produced in the same manner as in Example 2299.

Table 369 Table 370 1 RNM 2.04 (2H, m), 2.56 (2H, brs), 2.62 (2H, t, J = 7.0 Hz), 2.72 (2H, t, J = 5.5 Hz), 3.17 (2H, brs), 3.64 (2H, t, J = 6.5 Hz), 6.02 (1H, brs), 6.96 (2H, d, J = 2317 9. 0 Hz), 7.04 (2H, d, J = 9.0 Hz), 7.36 (2H, d, J = 9.0 Hz), 7.58 (3H, m), 7.70 (1H, dd, J = 8.5 Hz, 2.0 Hz), 7.77 (ÍH, brs), 7.98 (ÍH, d, J = 2.0 Hz).

Table 371 Table '372 Table 373 Table 374 122 Table 375 Table 376 eleven Example 2357 Production of 3,4-dichloro-N- [6- (4- {4- [(3,4-difluorobenzyl) methylamino] piperidine-1-carbonyl} phenoxy) pyridin-3-yl] benzamide 3,4-dichloro-N- dihydrochloride. { 6- [4- (4-methylamino-piperidine-1-carbonyl) phenoxy] pyridin-3-yl benzamide (114 mg, 0. 2 mmol) was dissolved in DMF (3 mL). To the resulting solution were added 4-bromomethyl-1,2-difluorobenzene (31 μL, 0.24 mmol) and potassium carbonate (111 mg, 0.8 mmol), and this solution was stirred for 4 hours at room temperature. The resulting reaction solution was concentrated under reduced pressure. The residue was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. This residue was purified by column chromatography on silica gel (chloroform: methanol = 50: 1), in order to produce 60 mg of the title compound. Appearance: White powder RNM (CDC13) d 1.64 (4H, brs), 1.84 (2H, brs), 2.20 (3H, s), 2.65-2.90 (3H, m), 3.54 (2H, s), 6.95-7.08 ( 4H, m), 7.13 (2H, d, J = 9.3 Hz), 7.41 (2H, d, J = 9.2 Hz), 7.57 (1H, d, J = 8.4 Hz), 7.75 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.03 (1H, d, J = 2.0 Hz), 8.15 (1H, dd, J = 8.9 Hz, 2.8 Hz), 8.30 (1H, brs), 8.31 (IH, d, J = 2.2 Hz ). The following compounds were produced in the same manner as in Example 2357. 11 6 Table 377 Table 378 Table 379 Table 380 Table 381 CH, 133 Table 382 Example 2444 Production of 1- (4-piperonylpiperazin-1-yl) -2- (4- [5- (4-trifluoromethylphenoxymethyl) pyridin-2-yloxy] -phenylamino} ethanone 4- [5- (4-trifluoromethylphenoxymethyl) ) pyridin-2-i loxi] f eni lamine (4.50 g, 12.5 mmol) was dissolved in DMF (150 mL). To the resulting solution were added potassium carbonate (2.60 g, 18.8 mmol) and sodium iodide (1.87 g). g, 12.5 mmol), and then to this solution was added 2-chloro-1- (4-piper oni Ipiper azi n-1-yl) ethanone (4.21 g, 12.5 mmol) The resulting solution was stirred for 11 hours under a nitrogen atmosphere at 80 ° C. The resulting reaction solution was concentrated under reduced pressure, ethyl acetate was added to the residue and washed with a saturated sodium bicarbonate solution and brine.The organic layer was dried over sulphate. of anhydrous magnesium, and evaporated, the residue was purified by column chromatography on silica gel (dichloromethane: methanol = 80: 1), or which produce 5.2 g of the title compound. Appearance: White powder XH RNM (CDC13) d 2.44-2.46 (4H, m), 3. 3-3. 7 (H, m), 3.69 (2H, t, J = 5.0 Hz), 3.86 (2H, s), 4.91 (1H, brs), 5.02 (2H, s), 5.94 (2H, s), 6.64 (2H , d, J = 8.9 Hz), 6.74- 135 6. 75 (2H, m), 6.85-6.89 (2H, m), 6.96-7.03 (4H, m), 7.55 (2H, d, J = 8.4 Hz), 7.72 (1H, dd, J = 8.4 Hz, 2.5 Hz ), 8.22 (1H, d, J = 2.0 Hz).

Example 2445 Production of N-. { 6- [4- (4-thiazol-2-ylmethylpiperazine-1-carbonyl) phenoxy] pyridin-3-yl} -4-trifluoromethyl-benzamide To a suspension of N- dihydrochloride. { 6- [4- (Piperazin-1-carbonyl) phenoxy] pyridin-3-yl} -4-trifluoromethylbenzamide (400 mg, 0.74 mmol) in 1,2-dichloroethane (20 mL) was added 2-formyl thiazole (125 mg, 1.10 mmol) and triethylamine (0.21 mL, 1.50 mmol). After the resulting solution was stirred at room temperature for 30 minutes, sodium triacetyloxy-borohydride (312 mg, 1.47 mmol) was added under cooling with ice. The reaction mixture was stirred at the same temperature for 30 minutes and at room temperature for 1 hour. Acetic acid (0.085 mL, 1.48 mmol) was added to the reaction mixture, and stirred at room temperature for 17 hours. The reaction mixture was poured into ice water, and extracted with chloroform. The chloroform layer was washed with a saturated sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate. A significant part of the solvent was evaporated. The white precipitate was then filtered and washed with ethyl acetate, thereby yielding 293 mg of the title compound. Appearance: White powder RNM (DMSO-d6) d 2.55 (4H, brs), 3.55 (4H, brs), 3.90 (2H, s), 7.15 (1H, d, J = 8.7 Hz), 7.16 (2H, d, J = 8.6 Hz), 7.45 (2H, d, J = 8.6 Hz), 7.68 (1H, d, J = 3.2 Hz), 7.73 (1H, d, J = 3.2 Hz), 7.94 (2H, d, J = 8.1 Hz), 8.17 (2H, d, J = 8.1 Hz), 8.26 (1H, dd, J = 8.7 Hz, 2.3 Hz), 8.55 (1H, d, J = 2.3 Hz), 10.68 (ÍH, s). The following compounds were produced in the same manner as in Example 2445.

Table 383 Table 384 Table 385 Table 386 Table 387 Table 388 Table 389 Example 2482 Production of N- (6- { 4- [4- ((SS, 2S) -2-hydroxy-cyclohexyl) piperazine-1-carbonyl] phenoxy}. Pyridin-3-yl) -4-trifluoromethylbenzamide To a solution of N- (6- [4- (piperazin-1-carbonyl) phenoxy] -pyridin-3-yl.} -4-trifluoromethyl-benzamide (430 mg, 0.91 mmol) in methanol was added 1, 2-epoxycyclohexane (180 mg, 1.83 mmol), and the resulting solution was stirred for 1 day under reflux. The resulting reaction solution was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform: methanol = 35: 1), and then ethyl acetate was added. The precipitated white powder was filtered and washed with ethyl acetate, to thereby yield 284 mg of the title compound. Appearance: White powder RNM (CDC13) d 1.03-1.38 (4H, m), 1.42-1.88 (3H, m), 2.06-2.35 (2H, m), 2.31 (2H, brs), 2.74 (2H, brs), 3.30-4.00 (6H, m), 7.00 (1H, d, J = 8.9 Hz), 7.15 (2H, d, J = 8.7 Hz), 7.43 (2H, d, J = 8.7 Hz), 7.77 (2H, d , J = 8.1 Hz), 8.02 (2H, d, J = 8.1 Hz), 8.21 (1H, brs), 8.22 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.33 (HI, d, J = 2.7 Hz).

Example 2483 Production of 3,4-dichloro-N- [6- (. {4- [3-oxo-3- (4-piperonylpiperazin-1-yl) propyl] phenyl] -methylamino) -pyridinium dioxalate 3-yl] benzamide To a solution of 3,4-dichloro-N- (6- { A - [3-oxo-3- (4-piperonylpiperazin-1-yl) propyl] phenylamino.} - pyridin- 3-yl) benzamide (250 mg, 0.395 mmol) in methanol (3 mL) was added acetic acid (0.500 mL) and 37% aqueous formaldehyde (0.640 mL, 7.89 mmol), and the resulting solution was stirred for 30 minutes at 50 ° C. To the reaction solution was added sodium cyanoborohydride (0.160 g, 2.55 mmol) at room temperature, and stirred for 8 hours at 50 ° C. Water was added to the reaction solution and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 10: 1) to produce a free form. This free form was dissolved in isopropanol (5 m) and oxalic acid dihydrate (70 mg, 0.555 mmol) by heating. The solvent was evaporated, and the resulting solid was recrystallized from isopropanol, to thereby yield 0.193 g of the title compound. Appearance: Pale yellow powder Melting point: 127 -129 ° C The following compound was produced in the same manner as in Example 2483.

Example 2484 2- (Ethyl (4- [5- (4-trifluoromethylphenoxymethyl) pyridin-2-yloxy] phenyl-lamino) -1- (4-piperonylpiperazin-1-yl) ethanone XU NMR (CDC13) d 1.18 (3H, t , J = 7.1 Hz), 2.41-2.44 (4H, m), 3.39-3.47 (4H, m), 3.51 (2H, brs), 3.64 (2H, brs), 4.03 (2H, s), 5.03 (2H, s), 5.94 (2H, s), 6.68 (2H, d, J = 9.1 Hz), 6.73-6.74 (2H, m), 6.85-6.88 (2H, m), 6.99 (2H, d, J = 9.1 Hz ), 7.01 (2H, d, J = 8.4 Hz), 7.55 (2H, d, J = 8.7 Hz), 7.71 (1H, dd, J = 8.6 Hz, 2.5 Hz), 8.22 (1H, d, J = 2.3 Hz).

Example 2485 Production of monohydrochloride 3,4-dichloro-N- [6- (4-thiomorpholin-4-ylmethylphenoxy) pyridin-3-yl] benzamide 3, -Dichloro-N- [6- (4-chloromethylphenoxy) -pyridin- 3-yl] benzamide (0.61 g, 1.5 mmol) was dissolved in DMF (5 mL). To the resulting solution were added triethylamine (0.84 mL, 6.0 mmol) and thiomorpholine (0.15 mL, 1.5 mmol), and this solution was stirred overnight at 40 ° C. The resulting reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate and washed with a saturated sodium bicarbonate solution and brine. The organic layer is dried over anhydrous magnesium sulfate and evaporated. This residue was purified by column chromatography on silica gel (chloroform: methanol = 80: 1). The solid obtained (0.56 g, 1.18 mmol) was dissolved in ethyl acetate (50 mL), and a solution of 4 N hydrogen chloride in ethyl acetate (0.295 mL, 1.18 mmol) was added, and this solution was stirred for 1 hour at room temperature. The precipitated crystals were collected by suction filtration, and recrystallized from methanol, to thereby yield 0.38 g of the title compound. Appearance: White Powder XU RNM (DMSO-d6) d 2.80-2.83 (2H, m), 3.09-3.17 (H, m), 3.61 (2H, m), 4.35 (2H, s), 7.14 (1H, d, J = 8.9 Hz), 7.21 (2H, d, J = 8.3 Hz), 7.60 (2H, d, J = 8.3 Hz), 7.85 (1H, d, J = 8.6 Hz), 7.96 (1H, dd, J = 8.3 Hz, 2.0 Hz), 8.23 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.24 (1H, d, J = 2.0 Hz), 8.53 (1H, d, J = 2.6 Hz), 10.45 (1H, brs), 10.62 (1H, brs). The following compounds were produced in the same manner as in Example 2485.

Example 2486 3,4-Dichloro-N- (4-. {4- [l- (3-imidazol-1-ylpropyl) -1,2,3,6-tetrahydropyridin-4-yl] phenoxy] phenyl ) -benzamide Melting point: 169-171 ° C Table 390 Table 391 Table 392 Table 393 Table 394 [54 Table 395 1101 Table 396 Table 397 Table 398 Table 399 Example 2551 Production of l- (3- {4- [4- (3,4-dichlorobenzoylamino) -phenoxy] phenyl} propionyl) -A- [2- (morpholino) acetyl] -piperazine To one solution of l-chloroacetyl-4- (3- { 4- [4- (3,4-dichlorobenzoylamino) phenoxy] phenyl}. propionyl) -piperazine (0.515 g, 0.896 mmol) and diisopropylethylamine (0.234 mL, 1.34 mmol ) in acetonitrile (11 mL) was added morpholino (0.117 mL, 1.34 mmol), and the resulting solution was refluxed for 1 hour. This reaction solution was concentrated under reduced pressure. To the residue was added a solution of saturated sodium bicarbonate, and extracted with chloroform. The chloroform layer was dried over anhydrous magnesium sulfate, and evaporated. The solid obtained was recrystallized from water-containing acetone, in order to produce 0.441 g of the title compound. Appearance: White powder Melting point: 187-190 ° C 163 The following compounds were produced in the same manner as in Example 2551.

Table 400 Table 401 1110 Table 402 Table 403 1112 Table 404 Table 405 Table 406 2580 4 -CF, Ph- -N N - - N (CH3) CH2 Ph pf l f - 190 2581 4 -CF3Ph ~ o pf 192- 193 The following compound was produced in the same manner as in Reference Example 860.

Example 2582 Ethyl ester of 1- acid. { 4- [5- (3, 4-Dichlorobenzoylamino) pyridin-2-yloxy] benzyl} piperazine-4-carboxylic Appearance: Pale yellow oil XH NMR (CDC13) d 1.25 (3H, t, J = 7.0 Hz), 1.76 (2H, m), 1.77 (2H, m), 2.03 (2H, t, J = 11.5 Hz), 2.28 (1H, m), 2.87 (2H, brd, J = 11.5 Hz), 3.48 (2H, s), 4.13 (2H, q, J = 7.0 Hz), 6.94 (1H, d, J = 9.0 Hz), 7.06 (2H, d, J = 8.5 Hz), 7.33 (2H, d, J = 9.0 Hz), 7.57 (1H, d, J = 8.5 Hz), 7.70 (1H, dd, J = 8.5 Hz , 2.0Hz), 7.88 (1H, brs), 7.97 (1H, d, J = 2.0 Hz), 8.17 (1H, dd, J = 9.0 Hz, 3.0 Hz), 8.24 (1H, d, J = 3.0 Hz) .

Example 2583 Production of 3,4-dichloro-N-. { 6- [A - (2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl) phenoxy] pyridin-3-yl} benzamide Hexamethyldisilazane (5 mL) was added to uracil (200 mg, 1.8 mmol), and the resulting solution was stirred for 5.5 hours at 150 ° C. The insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in a solution of acetonitrile (10 mL) -THF (5 mL), and to this solution were added 3,4-dichloro-N- [6- (4-chloromethylphenoxy) pyridin-3-yl] benzamide ( 500 mg, 1.2 mmol) and tin tetrachloride (3 drops). The resulting solution was refluxed for 2.5 hours. To this reaction solution was added methanol (1 mL), and the resulting solution was stirred for 30 minutes at room temperature. The resulting reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (methanol: chloroform = 1: 99-3: 97), to thereby produce 20 mg of the title compound. Appearance: White powder Y \ NMR (DMSO-d6) d 4.88 (2H, s), 5.61 (1H, dd, J = 7. 9 Hz, 2.3 Hz), 7.07-7.13 (3H, m), 7.35 (2H, d, J = 8.6 Hz), 7.79-7.85 (2H, m), 7.95 (1H, dd, J = 8.6 Hz, 2.0 Hz ), 8.18 (1H, d, J = 2.6 Hz), 8.22 (1H, d, J = 2.0 Hz), 8.47 (1H, d, J = 2.6 Hz), 10.55 (1H, s), 11.33 (1H, s) ).; MS: m / z 482 (M +).

Example 2584 Production of N- dihydrochloride. { 6- [4- (4-Benzyl-2-oxopiperazin-1-ylmethyl) phenoxy] pyridin-3-yl} -3, 4-dicJorobenzamide To a solution of 4-benzylpiperazin-2-one (0.56 g, 2. 95 mmol) in DMF (10 mL) was added 60% sodium hydride (0.12 g, 2.95 mmol), and this solution was stirred at room temperature for 30 minutes. 2- (-chloromethylphenoxy) -5-nitropyridine (0.78 g, 2.95 mmol) was added to the reaction mixture, and the mixture was stirred for 1 hour at room temperature. To this mixture was added brine (50 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The resulting oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added iron powder (0.33 g, 5.89 mmol). This solution was stirred for 2 hours at room temperature. The resulting reaction solution was concentrated under reduced pressure, and a saturated sodium bicarbonate solution (50 mL) was added to the residue. The obtained mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The remaining oil was dissolved in THF (10 mL). To the resulting solution were added triethylamine (0.21 mL, 1.47 mmol) and 3-benzoyl dichlorochloride (0.31 mL, 1.47 mmol), and this solution was stirred at room temperature for 2 hours. A solution of saturated sodium bicarbonate (50 mL) was added to the solution, and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform: methanol = 40: L). The oil obtained was dissolved in ethyl acetate (5 mL), and to the resulting solution was added a solution of 4 N hydrogen chloride in ethyl acetate (1.5 mL, 6 mmol). The white powder formed was collected by suction filtration, in order to produce 0.045 g of the title compound. Appearance: White powder RNM (DMSO-d6) d 3.5 (4H, m), 3.86 (2H, brs), 4. 42 (2H, s), 4.59 (2H, brs), 7.06-7.12 (3H, m), 7.34 (2H, d, J = 8.6 Hz), 7.48-7.51 (3H, m), 7.57-7.60 (2H, m), 7.84 (1H, d, J = 8.6 Hz), 7.97 (1H, dd, J = 2.0 Hz, 8.3 Hz), 8.18-8.24 (2H, m), 8.49 (1H, d, J = 2.6 Hz) , 10.61 (1H, s). The following compound was produced in the same manner as in Reference Example 656.

Example 2585 2- ( { 4- [5- (3, -Dichlorophenylamino) pyridin-2-yloxy] -2-trifluoromethylphenyl} ethylamino) -1- (4-piperonylpiperazin-1-yl) ethanone Yl NMR ( CDC13) d 1.02 (3H, t, J = 7.1 Hz), 2.30- 2.45 (4H, m), 3.22 (2H, q, J = 7.1 Hz), 3.40 (2H, s), 3.45- 3.65 (4H, m ), 3.85 (2H, s), 5.57 (1H, brs), 5.94 (2H, s), 6.65-6.80 (3H, m), 6.85 (1H, s), 6.95 (1H, d, J = 8.7 Hz) , 7.00 (1H, d, J = 2.7 Hz), 7.29-7.31 (2H, m), 7.39 (1H, d, J = 2.7 Hz), 7.53 (1H, dd, J = 8.7 Hz, 2.9 Hz), 7.64 (1H, d, J = 8.8 Hz), 7.99 (1H, d, J = 2.7 Hz). The following compounds were produced in the same manner as in Reference Example 658.

Table 407 Table 408 Example 2596 Production of 3- (4-. {5- [4- (3,4-dichlorophenyl) piperazin-1-yl] pyridin-2-yloxy} phenyl) -1- (4-pipedonylpiperazine-1 il) propan-l-one To a solution of 3- [4- (5-bromopyridin-2-yloxy) phenyl] -1- (4-piperonylpiperazin-1-yl) propan-1-one (359) mg, 0.69 mmol) and 1- (3,4-dichlorophenyl) -piperazine (206 mg, 0.89 mmol) in toluene (16 mL) were added with Pd2 (dba) 3 (25 mg, 0.027 mmol), Xantphos (32 mg). mg, 0.055 mmol) and sodium t-butoxide (99 mg, 1.03 mmol), and the resulting solution was refluxed under an argon atmosphere for 3 hours. The solution was allowed to cool, water was added to this reaction mixture. The resulting solution was extracted with dichloromethane, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 30: 1), thereby producing 236 mg of the title compound. Appearance: Pale yellow powder XH RNM (CDC13) d 2.31-2.40 (4H, m), 2.58-2.6 (2H, m), 2.92-2.98 (2H, m), 3.23-3.38 (8H, m), 3.41 (4H , brs), 3.63 (2H, t, J = 4.9 Hz), 5.94 (2H, s), 6.72-6.73 (2H, m), 6.78 (1H, dd, J = 8.9 Hz, 2.8 Hz), 6.84-6.90 (2H, m), 6.99-7.06 (3H, m), 7.19-7.24 (3H, m), 7.32 (1H, dd, J = 9.4 Hz, 3.1 Hz), 7.88 (HI, d, J = 3.0 Hz) . Tris (dibenzylidenacetone) dipaladium is abbreviated Pd2 (dba) 3. Henceforth in the present, it means the same. 4, 5-bis (diphenylphosphino) -9,9-dimethylxantene is abbreviated Xantphos. Henceforth in the present, it means the same. The following compounds were produced in the same manner as in Example 2596.

Table 409 The following compounds were produced in the same manner as in Reference Example 659.

Table 410 Table 411 Example 2608 Production of 1- (3,4-dimethoxybenzyl) -3-. { 3-methyl-4- [5- (4-trifluoromethylphenylethynyl) pyridin-2-yloxy] phenyl} tetrahydropyrimidin-2-one To a solution of 1- [4- (5-bromopyridin-2-yloxy) -3-methylphenyl] -3- (3,4-dimethoxybenzyl) tetrahydropyrimidin-2-one (0.3 g, 0.59 mmol) in IV-methylpyrrolidone (10 mL) was added bis (trif enylf osf in) palladium bichloride (20 mg, 0.03 mmol), copper iodide (11 mg, 0.059 mmol), 4-ethynyl-a, a, a- trifluorotoluene (0.14 mL, 0.88 mmol) and triethylamine (0.14 mL, 10 mmol) under a nitrogen atmosphere. The resulting solution was stirred for 3 hours at 110 to 120 ° C. After being allowed to cool, water was added to the reaction solution. The resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was then evaporated, and the residue was purified by chromatography on silica gel (r-hexane: ethyl acetate = 4: 1 - >; 1: 1), in order to produce 0.28 g of the title compound. Appearance: Pale coffee amorphous powder XU RNM (CDCI3) d 1.97-2.15 (2H, m), 2.16 (3H, s), 3.31 (2H, t, j = 6.0 Hz), 3.72 (2H, t, J = 6.0 Hz ), 3.88 (3H, s), 3.89 (3H, s), 4.57 (2H, s), 6.72-6.95 (5H, m), 7.04 (HH, d, J = 8.6 Hz), 7.17 (HH, dd, J = 2. 6 Hz, 8.6 Hz), 7.55-7.68 (4H, m), 7.78 (1H, dd, J = 2.3 Hz, 8.6 Hz), 8.36 (1H, d, J = 2.3 Hz).

Example 2609 Production of 3- (3-methyl-4-. {5- [2-oxo-2- (4-trifluoromethylphenyl) ethyl] pyridin-2-yloxy} phenyl) -1-piperonyltetrahydropyrimidin-2 hydrobromide. -one To a solution of 3- [4- (5-bromopyridin-2-yloxy) -3-methylphenyl] -l-piperonyltetrahydropyrimidin-2-one (0.11 g, 0.22 mmol) in toluene (10 L) was added Pd2 (dba) 3 (10 mg, 0.01 mmol) and Xantphos (15 mg, 0.03 mmol) under a nitrogen atmosphere. The resulting solution was stirred for 5 minutes, and then 4'- (trifluoromethyl) acetophenone (63 mg, 0.33 mmol) and potassium bis (trimethylsilyl) amide (66 mg, 0.33 mmol) were added to the reaction solution. The resulting solution was stirred at 70 to 80 ° C for 30 minutes, and allowed to cool. Water was added to the reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 2: 1 -> 1: 1), to yield 50 mg of a free form. To this free form was added an equivalent amount of hydrobromic acid, thereby producing 50 mg of the title compound. Appearance: Colorless amorphous powder 179 XU NMR (DMSO-d6) d 1.85-2.10 (2H, m), 2.06 (3H, s), 3.14-3.47 (2H, m), 3.50-3.76 (2H, m), 4.40 (2H, s), 4.49 (2H, s), 4.70-5.40 (HH, m), 5.98 (2H, s), 6.70-6.80 (HH, m), 6.81-6.90 (2H, m), 6.90-7.04 (2H, m), 7.12 (1H, d, J = 2.2 Hz, 8.6 Hz), 7.18-7.26 (1H, m), 7.72 (1H, dd, J = 2.2 Hz, 8.5 Hz), 7.93 (2H, d, J = 8.2 Hz), 7.95-8.02 (ÍH, m), 8.24 (2H, d, J = 8.2 Hz). The following compounds were produced in the same manner as in Example 2609.

Table 412 Table 413 The following compounds were produced in the same manner as in Reference Example 111.

Table 414 181 Table 415 Table 416 Example 2623 Production of 2- [4- (3- {4- [4- (3,4-dichlorobenzoylamino) -phenoxy] phenyl} propionyl) piperazin-1-yl] acetic acid hydrochloride To a solution of 2- [4- (3- { 4- [4- (3, 4-dichlorobenzoylamino) phenoxy] phenyl] propionyl) piperazin-1-yl] ethyl acetate (0.493 g, 0.843 mmol) in THF ( 5 mL) and ethanol (5 mL) were added 5 M aqueous sodium hydroxide (0.253 mL, 1.27 mmol) and water (1 mL), and the resulting solution was refluxed for 1 hour. This reaction solution was concentrated under reduced pressure, and the residue was dissolved in 50% aqueous ethanol. To the resulting solution was added M hydrochloric acid (0.253 L, 1.27 mmol), and the solid obtained was collected by filtration. This solid was dissolved in ethanol (10 mL) and 5 M hydrochloric acid (0.3 mL) by heating. The solvent was then evaporated, and the solid obtained was recrystallized from ethanol-diethyl ether, to thereby yield 0.381 g of the title compound. Appearance: White powder Melting point: 215-218 ° C The following compounds were produced in the same manner as in Example 2623.

Table 417 Table 418 11 5 Table 419 Table 420 (DMSO-d6) 1.13 (3H, t J = 7 .0 Hz) 2 20-2.50 4H, m), 3 30-3.60 (8H, m), 4 21 (2H, s), 5 .99 (2H, s), 6. 60-7 05 (7H, m) 3,4- Pipero-, 7 .30- 2643 -N (C2H5) - -CH, -CO- 7 40 (1H, Cl, PhNHCO- m) nyl 7 47 (1H, d, J = = 8 Hz), 7.65-7.85 (lH, m), 7.90 (IH, d, J i 2.3 Hz), 8.06 (1H, d, J = 2.6 Hz), 9.80 (2H , brs), 12.40 (1H, brs).

Table 421 Table 422 Table 423 Table 424 192 Table 425 Example 2664 Production of; 4-. { 5- [(4-trifluoromethylphenyl) amino) -methyl] -pyridin-2-yloxy} phenyl) (4-piperonylpiperazin-1-yl) methanone 6- [4- (4-piperonylpiperazine-1-carbonyl) phenoxy] pyridin-3-yl ester of methanesulfonic acid (0.433 g, 0.824 mmol) and 4-tr if luoromethyl ester phenylamine (0.310 mL, 2.47 mmol) were mixed together, and the resulting mixture was stirred for 2 hours at 100 ° C. The yellow mass formed stirred together with a solution of saturated sodium bicarbonate, ethyl acetate and THF (20 ml of each). The organic layer was collected, washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 50: 1), in order to produce 0.236 g of the title compound. Appearance: Pale yellow amorphous powder XU RNM (CDC13) d 2.44 (4H, brs), 3.45 (2H, s), 3.57 (2H, brs), 3.75 (2H, brs), 4.30 - .35 (ÍH, m), 4.36 (2H, s), 5.95 (2H, s), 6.63 (2H, d, J = 8.7 Hz), 6.74-6.77 (2H, m), 6.85 (1H, s), 6.93 (1H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.4 Hz), 7.39- 7.47 (4 H, m), 7.71 (1H, dd, J = 2.5 Hz, 8.4 Hz), 8.18 (1H, d, J = 2.3 Hz). The following compounds were produced in the same manner as in Example 2664.

Table 426 194 EXAMPLE 2668 Production of 2- (methyl-. {4- [5- (5-trifluoromethyl-pyridin-2-yloxymethyl) pyridin-2-yloxy] phenyl} amino) -1- (4-piperonylpiperazine-1- il) ethanone It was dissolved 2-. { [4- (5-hydroxymethylpyridin-2-yloxy) phenyl] methylamino} -l- (4-piperonylpiperazin-1-yl) ethanone (0.98 g, 2.0 mmol) in EMF (30 mL). To the resulting solution was added 60% sodium hydride (60%, 88 mg, 2.2 mmol) under cooling with ice, and 195 this solution was stirred for 30 minutes at 0 ° C. To the reaction solution was added 2-chloro-5- (trifluoromethyl) pyridine (0.36 g, 2.0 mol), and this solution was stirred under a nitrogen atmosphere for 3 hours at 60 ° C. The resulting reaction solution was concentrated under reduced pressure. To the residue was added ethyl acetate, and this solution was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (n-hexane: ethyl acetate = 1: 5), to thereby yield 0.68 g of the title compound. Appearance: White Powder XU RNM (CDC13) d 2.41-2.44 (4H, m), 3.02 (3H, s), 3.43 (2H, s), 3.48 (2H, brs), 3.63 (2H, brs), 4.08 (2H , s), 5.37 (2H, s), 5.94 (2H, s), 6.68-6.77 (4H, m), 6.81-6.84 (3H, m), 7.00 (2H, d, J = 9.1 Hz), 7.72- 7.79 (2H, m), 8.27 (1H, d, J = 2.3 Hz), 8.44 (1H, brs). The following compounds were produced in the same manner as in Example 2668.

Table 427 Example 2672 3,4-Dichloro-N-. { 6- [4- (3,5-dioxoisoxazolidin-4-ylidenemethyl) phenoxy] pyridin-3-yl} benzamide To a solution of hydroxylamine hydrochloride (500 mg, 1.0 mmol) in water (0.2 mL) was added sodium carbonate (1.05 g, 9.91 mmol) and a solution of dimethyl ester of 2- acid. { 4- [5- (3,4-dichlorobenzoylamino) pyridin-2-yloxy] benzylidene malonic acid (500 mg, 1.0 mmol) in THF (5 mL). Methanol (5 mL) was subsequently added to the resulting solution and stirred for 8 hours at 60 ° C. The reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 30: 1). To the resulting white precipitate was added ethyl acetate, filtered and the filtrate was washed with diethyl ether, thereby yielding 105 mg of the title compound. Appearance: White powder? U RNM (DMSO-d6) d 7.12 (ÍH, d, J = 8.9 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.63 (2H, d, J = 8.8 Hz), 7.84 (1H, d, J = 8.4 Hz), 7.95 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.15 (1H, s), 8.22 (1H, dd, J = 8.9 Hz, 2.6 Hz), 8.22 ( 1H, d, J = 2.0 Hz), 8. 51 (1H, d, J = 2.6 Hz), 10.57 (1H, s), 11.16 (1H, s).

Example 2673 Production of 3,4-dichloro-N- monohydrochloride. { 6- [4- (5-methyl- [1,2,4] oxadiazol-3-ylmethyl) phenoxy] pyridin-3-yl} benzamide A 3, 4-dichloro-N-. { 6- [4- (N-Acetoxycarbamimidoyl-methyl) phenoxy] pyridin-3-yl} Benzamide (340 mg, 0.788 mmol) was added acetic acid (4 mL), and the resulting solution was stirred under reflux for 10 minutes. This reaction solution was concentrated under reduced pressure. To the residue was added a solution of saturated sodium bicarbonate, and the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel (chloroform: methanol = 40: 1), and the residue obtained was dissolved in ethyl acetate (5 mL). To this solution was added a solution of 4 N hydrogen chloride in ethyl acetate until the compound did not precipitate further. The white powder obtained was filtered, and washed with diethyl ether, thereby producing 154 mg of the title compound. Appearance: XU white powder RNM (DMSO-de) d 2.55 (3H, s), 4.05 (2H, s), 7.07 (1H, d, J = 8.7 Hz), 7.07 (2H, d, J = 8.6 Hz), 7.33 (2H, d, J = 8.6 Hz), 7.83 (1H, d, J = 8.4 Hz), 7.96 (1H, dd, J = 8.4 Hz, 2.0 Hz), 8.21 (1H, dd, J = 8.7 Hz, 2.6 Hz), 8.24 ( 1H, d, J = 2.0 Hz), 8.48 (1H, d, J = 2.6 Hz), 10.62 (1H, s).

Example 2674 Production of 1- (3- {4- [5- (3, -dichlorobenzoylamino) -2-pyridylmethyl] phenyl} propionyl) -4-piperoniIpiperazine monohydrochloride To a solution of 3- (4- { 5- [bis (3,4-dichlorobenzoyl) amino] -2-pyridylmethyl}. Phenyl) ethyl propionate (177 mg, 0.281 mmol) in THF (5 mL) and ethanol (5 mL) were added 5 M aqueous sodium hydroxide (0.0929 mL, 0.463 mmol) and water (1 mL), and the resulting solution was refluxed. for 1 hour. To this reaction solution was added 5 M hydrochloric acid (0.12 mL), and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was dissolved in DMF (3 mL), and to the resulting solution was then added 1-piperonylpiperazine (102 mg, 0.463 mmol), triethylamine (0.137 mL, 0.983 mmol) and diethyl cyanophosphate (0.0703 mL, 463 mmol), and stirred for 1.5 hours at room temperature. Water was added to the resulting reaction solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried on anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatography (dichloromethane: methanol = 70: 1 -> 40: 1 -> 20: 1), thereby producing 44.1 mg of a free form. This free form was dissolved in ethanol (5 mL) and 5 M hydrochloric acid (0.03 mL) by heating. The solvent was then evaporated, and the solid obtained was recrystallized from isopropanol containing water, thereby producing 19.6 mg of the title compound. Appearance: Pale yellow powder Melting point: 181-183 ° C Example 2675 Production of N- (6-) {4- [4- (5-oxo-4,5-dihydro- [1, 3, 4] oxadiazol-2-ylmethyl) piperazine-1-carbonyl] monooxalate phenoxy) pyridin-3-yl) -4-trifluoromethylbenzamide to a suspension of N- trichlorohydrate. { 6- [4- (4-Hydrazinocarbonyl-methylpiperazin-1-carbonyl) phenoxy] pyridin-3-yl} -4-tr i f luoromethylbenzamide (300 mg, 0.46 mmol) in THF (7 mL) was added triethylamine (0.29 mL, 2.08 mmol), and the resulting solution was stirred for 10 minutes at room temperature. It was added to the solution N, N '-carboni ldi imide zol (97 mg, 0.60 mmol) under cooling with ice, and the resulting solution was stirred for 1 hour at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added a solution of saturated sodium bicarbonate, and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was then purified by column chromatography on silica gel (chloroform: methanol = 15: 1). The obtained residue was dissolved in ethanol, and oxalic acid was added to the resulting solution. Ethanol was evaporated under reduced pressure, after which the solidified white matter was filtered, and washed with diethyl ether, thereby yielding 140 mg of the title compound. Appearance: XU white powder RNM (DMSO-d6) d 2.31 -2.69 (4 H, m), 3.53 (2H, s), 3.53 (4H, brs), 7.16 (1H, d, J = 8.9 Hz), 7.17 ( 2H, d, J = 8.5 Hz), 7.45 (2H, d, J = 8.5 Hz), 7.94 (2H, d, J = 8.1 Hz), 8.17 (2H, d, J = 8.1 Hz), 8.26 (1H, dd, J = 8.9 Hz, 2.7 Hz), 8.55 (1H, d, J = 2.7 Hz), 10.67 (1H, s), 12.27 (1H, s).

Example 2676 Production of 4- (4- { 4- [4- (3,4-dichlorobenzoylamino) -2-fluorophenoxy] phenyl} -4-hydroxybutyryl) morpholine To a suspension of 4 - (4 -. { 4 - [4 - (3, 4 - dichlorobenzoylamino) -2-f luorophenoxy] phenyl} -4-oxobutyryl) morpholine (1.00 g, 1.83 mmol) in THF (20 mL) and methanol (5 mL) was added sodium borohydride. (0.0694 g, 1.83 mmol), and the resulting solution was stirred for 1 hour at room temperature. To this reaction solution was added water and saturated aqueous ammonium chloride and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, evaporated and the residue was purified by column chromatography on silica gel. (dichloromethane: methanol = 30: 1). The solid obtained was recrystallized from isopropanol containing water, in order to produce 0.850 g of the title compound. Appearance: White powder Melting point: 108-111 ° C The following compounds were produced in the same manner as in Example 2676.

Table 428 Table 429 Table 430 Example 2685 Production of. { 6- [4- (4-piperonylpiperazin-1-ylmethyl) phenoxy] pyridin-3-ylmethyl} - (4-trifluoromethylphenyl) amine To a suspension of lithium aluminum hydride (0.106 g, 2.80 mmol) in THF (10 mL) was added dropwise a solution of 6- [4- (4-piperonylpiperazine-1-carbonyl) -phenoxy] -N- (4-trifluoromethylphenyl) nicotinamide (0.423 g, 0.700 mmol) in THF (10 mL) under ice-cooled stirring. Once the entire amount was added by dripping, the temperature of the solution was slowly raised and stirred under reflux for 2 hours. After cooling, ice water (50 mL) was added to the solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 40: 1), to thereby produce 0.125 g of the title compound. Appearance: Pale yellow MS 576 oil (M +) The following compounds were produced in the same manner as in Example 2685.

Example 2686 N- [6- (2-Fluoro-4-. {Methyl (2- (4-piperonylpiperazin-1-yl) ethyl] amino} phenoxy) pyridin-3-yl] -3,4-dichlorobenzenesulfonamide XU RNM (CDC13) d 2.50-2.55 (10H, m), 2.92 (3H, s), 3.41-3.45 (4H, m), 5.93 (2H, s), 6.39-6.49 (2H, m), 6.73-6.74 (2H, m), 6.84-6.89 (2H, m), 6.99 (1H, t, J = 9.1 Hz), 7.42-7.70 (4H, m), 7.81 (ÍH, brs).

Example 2687 Production of hydrobromide 3- (3-methyl-4-. {5- [2- (4-trifluoromethyl-phenyl) ethyl] pyridin-2-yloxy} phenyl) -l-piperonyl-tetrahydropyrimidin-2- a solution of 3- (3-methyl-4- (5- [(E) -2- (4-trifluoromethylphenyl) vinyl] pyridin-2-yloxy} phenyl) -1-piperonyl tetrahydropyrimidin-2-one (0.16 g, 0.27 mmol) in ethyl acetate ethyl acetate (15 mL) was added 5% platinum-carbon (0.05 g) under a nitrogen atmosphere, and the resulting solution was then stirred under a hydrogen atmosphere for 4.5 hours at room temperature. The resulting reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate: = n-hexane 1: 4-1: 2), and to the resulting product was added hydrobromide, to thereby produce 50 mg of the title compound. Appearance: Colorless amorphous powder XU RNM (DMSO-de) d 1.85-2.09 (5H, m), 2.77-3.02 (4H, m), 3.15-3.33 (2H, m), 3.55-3.70 (2H, m), 3.75 -4.15 (HH, m), 4.40 (2H, s), 5.99 (2H, s), 6.76 (1H, dd, J = 1.5 Hz, 7.8 Hz), 6.80-6.98 (4H, m), 7.10 (1H, dd, J = 2.6 Hz, 8.5 Hz), 7.19 (1H, d, J = 2.6 Hz), 7.44 (2H, d, J = 8.1 Hz), 7.62 (2H, d, J = 8.1 Hz), 7.71 (1H , dd, J = 2.4 Hz, 8.4 Hz), 7.91 (1H, d, J = 2.4 Hz). The following compounds were produced in the same manner as in Reference Example 673.

Table 431 Example 2692 Production of l- [3- (4-. {L- [5- (3,4-Dichlorobenzoylamino) -2-pyridyl] -1-hydroxyimino} methylphenyl) propionyl] -4-piperonylpiperazine To one solution of 1- (3- (4- [5- (3,4-dichloro-benzoylamino) pyridine-2-carbonyl] phenyl Jpropionyl) -4-piperonyl piperazine (0.330 g, 0.511 mmol) in pyridine (7 mL) was hydroxylamine hydrochloride (53.3 mg, 0.767 mmol) was added, and the The resulting solution was refluxed for 0.5 hour. The reaction solution was concentrated under reduced pressure, and brine was added to the residue. This solution was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 15: 1), whereby 0.225 g of the title compound was obtained as a mixture of the syn form and the anti (1: 1) form of the oxime. Appearance: Colorless amorphous powder XH NMR (CDC13) d 2.21-2.39 (4H, m), 2.49-2.60 (2H, m), 2.78-2.90 (2H, m), 3.29-3.44 (4H, m), 3.55 (2H , s), 5.90 (2H, s), 6.62-6.73 (2H, m), 6.80 (1H, s), 7.07 (1H, d, J = 7.7 Hz), 7.12 (1H, d, J = 7.7 Hz) , 7.15-7.30 (2.5H, m), 7.39 (0.5H, d, J = 8.4 Hz), 7.42 (0.5H, d, J = 8.4 Hz), 7.45-7.51 (0.5H, m), 7.62-7.74 (1H, m), 7.94 (0.5H, d, J = 2.0 Hz), 7.99 (0.5H, d, J = 2.0 Hz), 8.09-8.28 (HI, m), 8.62 (0.5H, s), 8.85 (0.5H, s), 9.40 (0.5H, brs), 9.62 (0.5H, brs), 10.21 (0.5H, brs), 13.85 (0.5H, brs).

Example 2693 Production of 4- (2-oxo-3- {4- [5- (4-trifluoromethylbenzoylamino) pyridin-2-yloxy] phenyl} propionyl) -piperazine-1-carboxylic acid t-butyl ester To a solution of 4- (2-) t-butyl ester. hydroxy-3-. { 4- [5- (4-trifluoromethylbenzoylamino) pyridin-2-yloxy] phenyl} propionyl) piperazine-1-carboxylic acid (0.58 g, 0.94 mmol) in dichloromethane (4 mL) was added a Dess-Ma.rtin reagent (0.8 g, 1.89 mmol) and the resulting solution was then stirred under a gas flow of nitrogen for 4 hours at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added 1N aqueous sodium hydroxide (50 mL), and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by chromatography on silica gel (dichloromethane: methanol = 50: 1), to yield 0.31 g of the title compound. Appearance: Yellow powder XH RNM (CDC13) d 1.4K9H, s), 2.99-3.22 (4H, m), 3. 25-3.41 (2H, m), 3.42-3.60 (2H, m), 4.04 (2H, s), 6.97 (1H, d, J = 8.9 Hz), 7.10 (2H, d, J = 8.4 Hz), 7.27 (2H, d, J = 8.4 Hz), 7.73 (2H, d, J = 8.0 Hz), 7.99 (2H, d, J = 8.0 Hz), 8.13 (1H, d, J = 2.8 Hz), 8.30 (1H , dd, J = 8.9 Hz, 2.8 Hz), 8.45 (1H, brs).

Example 2694 Production of 3,4-dichloro-N-. { 3-fluoro-4- [4- (1-hydroxy-2-morpholino-4-ylethyl) phenoxy] phenyl} benzamide 3,4-Dichloro-N-. { 3-fluoro-4- [4- (l-hydroxy-2-morpholino-4-ylethyl) phenoxy] phenyl} benzamide (37.4 g) was recrystallized from ethanol (700 mL) to yield 34.34 g of the title compound. Appearance: White powder Melting point: 175-176 ° C Example 2695 Production of N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-fluorophenoxy) pyridin-3-yl] -3, 4-Dichlorobenzenesulfonamide N_ [5_ (4_ { [2- (4-Piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-fluorophenoxy) pyridin-3-yl] -3,4-dichlorobenzenesulfonamide ( 8.15 g) was recrystallized from ethanol (60 mL) to yield 7.78 g of the title compound. Appearance: White powder Melting point: 163-166 ° C Example 2696 Production of N- [6- (4-. {[2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4- trifluoromethylbenzamide N- [6- (4- { [2- (4-Piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide ( 5.1 g, 7.7 mmol) was recrystallized from acetone (15 mL) to yield 3.7 g of the title compound. Appearance: White powder Melting point: 128-131 ° C Example 2697 Production of N-. { 6- [4- (4-benzylpiperazin-1-carbonyl) phenoxy] pyridin-3-yl} -4-trifluoromethylbenzamide N-. { 6- [4- (4-Benzylpiperazin-1-carbonyl) -phenoxy] pyridin-3-yl} -4-trifluoromethylbenzamide (78.86 g) was recrystallized from ethanol (530 mL) to yield 96.66 g of the title compound. Appearance: White needles Melting point: 177.6-179.2 ° C Example 2698 Production of N- (6-. {4- [4- (2-oxo-l, 2,3,4-tetrahydro-quinolin-6-ylmethyl) piperazine-1-carbonyl] phenoxy] -din -3-yl) -4-trifluoromethylbenzamide To a solution of 4- [5- (4-trifluoromethylbenzoyl-amino) din-2-yloxy] benzoic acid (4.30 g, . 7 mmol) in DMF (150 mL) was added 1- (2-oxo-1,2,3,4-tetrahydroquinolin-6-ylmethyl) -piperazine (2.6 g, 10.7 mmol), 1-hydroxybenzotriazole monohydrate (1.64 mmol). g, 10.7 mmol) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (2.46 g, 12.8 mmol) under cooling with ice, and the resulting solution was stirred for 1 hour under cooling with ice and for 17 hours at room temperature. This solution of The reaction was concentrated under reduced pressure. To the residue was added a solution of saturated sodium bicarbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from ethyl acetate, to thereby yield 5.24 g of the title compound. Appearance: White powder Melting point: 250. 5-252. 5 ° C EXAMPLE 2699 Production of N- (6-. {4- [4- (4-benzylpiperidine-1-carbonyl) piperazine-1-carbonyl] phenoxy] din-3-yl) -3-dichlorobenzamide To one solution of acid 1-. { 4- [5- (3,4-dichlorobenzoylamino) din-2-yloxy] benzoyl} piperidine-4-carboxylic acid (4.5 g, 8.8 mmol) in DMF (88 mL) was added 1-benzylpiperazine (1.83 mL, 10.5 mmol), 1-hydroxybenzotriazole monohydrate (1.61 g, 10.5 mmol) and 1-ethyl hydrochloride 3- (3-dimethylaminopropyl) carbodiimide (2.02 g, 10.5 mmol) under ice-cooling, and the resulting solution was stirred overnight at room temperature. To this reaction solution was added a solution of saturated sodium bicarbonate, and the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was washed with a solution of saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was recrystallized from isopropyl alcohol (700 mL), thereby producing 3.2 g of the title compound. Appearance: White powder Melting point: 223-225 ° C Example 2700 Production of N- [6- (4-. {[2- (4-benzylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) din-3-yl] -4- trifluoromethylbenzamide To a suspension of 1- (4-benzylpiperazin-1-yl) -2-. { methyl [3-methyl-4- (5-nitrodin-2-yloxy) phenyl] -amino} Ethanone (2.85 g, 6.0 mmol) in ethyl acetate (30 mL) was added with 5% platinum-carbon (0.30 g) under a nitrogen atmosphere, and the resulting solution was stirred for 3 hours at 40 ° C under a hydrogen atmosphere. The platinum-carbon was separated with Celite, and the filtrate was concentrated. The residue was dissolved in THF (30 mL), and triethylamine (1.26 mL, 9.1 mmol) was added to this solution under cooling with ice. To the resulting solution was then added dropwise 4- (trifluoromethyl) benzoyl chloride (1.16 mL, 7.8 mmol). This reaction solution was stirred overnight, then a solution of saturated sodium bicarbonate was added thereto, and the mixture was extracted with ethyl acetate. The Ethyl acetate layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (dichloromethane: methanol = 20: 1). The resulting product was then recrystallized from a mixed solvent consisting of diisopropyl ether-acetone, to thereby yield 1.37 g of the title compound. Appearance: White powder Melting point: 112-113 ° C Example 2701 Production of (4-benzylpiperazin-1-yl) (4- {5 - [methyl (4-trifluoromethylbenzyl) amino] din-2-yloxy} phenyl) -methanone To a solution of (4-benzylpiperazine) -l-il). { 4- [5- (4-trifluoromethylbenzylamino) din-2-yloxy] phenyl} methanone (5.40 g, 9.88 mmol) in methanol (150 mL) was added 37% aqueous formaldehyde (2.8 mL)sodium cyanoborohydride (1.86 g, 29.6 mmol) and acetic acid (1.7 mL) under ice-cooling, and the resulting solution was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure. Water was added to the residue, and this solution was neutralized with a saturated sodium bicarbonate solution and extracted with chloroform. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. He The solvent was evaporated, and the residue was purified by column chromatography on silica gel (chloroform: methanol = 60: 1). To the resulting product was added a solution of 4 M hydrogen chloride in ethyl acetate until the resulting solution had a pH of 1. The precipitates were collected by filtration and recrystallized from ethanol (80 mL), thereby producing 2.5 g of the title compound. Appearance: White powder Melting point: 180-183.5 ° C Example 2702 Production of 4-piperonylpiperazine-l-carboxyl-4- [5- (3,4-dichlorobenzoylamino) pyridin-2-yloxy] benzylamide hydrochloride To a solution of 4-piperonylpiperazine-1-carboxyl-4- (5- aminopyridin-2-yloxy) benzylamide (2.48 g, 5.4 mmol) in THF (50 mL) was added triethylamine (0.9 mL, 6.5 mmol) and 3-dichlorobenzoyl chloride (1.13 g, 5.4 mmol) under ice-cooling, and the resulting solution was stirred under cooling with ice for 10 minutes. Water was added to the residue and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel [215 (dichloromethane: methanol = 25: 1) to yield 2.97 g of a white powder. This white powder was dissolved in ethanol (45 mL), and a solution of 4 M hydrogen chloride in ethyl acetate was added to the resulting solution until the solution had a pH of 1. The precipitates were collected by filtration and recrystallized of 83% ethanol (36 mL), in order to produce 2.72 g of the title compound. Appearance: White powder Melting point: 243. 5-246. 5 ° C Example 2703 Production of N- [6- (4-. {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin-3 -yl] -4-trifluoromethylbenzenesulfonamide N- [6- (4-. {4- [2- (4-Piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzenesulfonamide (1.35 g) was recrystallized from ethanol (20 mL) to yield 1.23 g of the title compound. Appearance: White powder Melting point: 156-158 ° C Example 2704 Production of N- (6-. {4- [4- (4-piperonylpiperazin-1-carbonyl) piperidin-1-yl] phenoxy] pyridin-3-yl) -3,4-dichlorobenzenesulfonamide N- (6- (4- [4- (4-Piperonylpiperidin-1-carbonyl) piperidin-1-yl] phenoxy] pyridin-3-yl) -3, -dichlorobenzenesulfonamide (1.95 g) was recrystallized from ethanol (35 mL ) to produce 1.70 g of the title compound Appearance: White powder Melting point: 130-133 ° C Example 2705 Production of N- [6- (4-. {[2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4- trifluoromethylbenzamide N- [6- (4- ([2- (4-Piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide (0.86 g, 1.30 mmol) was recrystallized from a mixed solvent of aceton (3 mL) diethyl ether (4 mL) and n-hexane (1 mL) to yield 0.72 g of the title compound Appearance: Pale yellow powder Melting point: 154-155 ° C Example 2706 Production of N- (6-. {4- [4- (4-benzylpiperazine-1-carbonyl) piperidin-1-yl] phenoxy] pyridin-3-yl) -4-trifluoromethyl benzensulfonamide N- ( 6- { 4- [4- (-Benzypiperidin-1-carbonyl) piperidin-1-yl] phenoxy] pyridin-3-yl) -4-trifluoromethylbenzenesulfonamide (1.55 g) was recrystallized from ethanol (60 mL) to produce 1.41 g of the title compound. Appearance: White powder Melting point: 199-201 ° C Example 2707 Production of N- [6- (4-. {4- [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin-3 -yl] -3,4-dichlorobenzenesulfonamide To a solution of (1- {4- [5- (3,4-dichlorobenzenesulfonylamino) pyridin-2-yloxy] -3-methylphenyl}. piperidin-4-yl} ) acetic acid (1.70 g, 3.1 mmol) and 1-benzylpiperazine (0.71 g, 4.0 mmol) in DMF (40 mL) were added triethylamine (1.08 mL, 7.8 mmol) and diethyl cyanophosphonate (0.76 g, 4.3 mmol) under cooling with ice, and the resulting solution was stirred for 1 hour under cooling with ice. To this reaction solution was added a solution of saturated sodium bicarbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with a solution of saturated sodium bicarbonate and brine, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 40: 1), after which the resulting product was recrystallized from ethanol, thereby producing 1.61 g of the title compound. Appearance: White needles Melting point: 151-155 ° C Example 2708 Production of N- [6- (4. {[2- (4-benzothiazol-6-ylmethylpiperazin-1-yl) -2-oxoethyl] methylamino] -phenoxy) pyridin-3-yl dihydrochloride ] -3,4-dichlorobenzamide To a solution of ({4- [5- (3,4-dichlorobenzoyl-amino) pyridin-2-yloxy] phenyl} methylamino) acetic acid (1.02 g, 2.3 mmol) and 1- (benzothiazol-6-ylmethyl) -piperazine (0.58 g, 2.5 mmol) in DMF (15 mL) were added triethylamine (0.95 mL, 6.9 mmol) and diethyl cyanophosphonate (0.447 mL, 2.7 mmol) under cooling with ice, and the resulting solution was stirred for 30 minutes under ice cooling and for 45 minutes at room temperature. Water was added to the solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (dichloromethane: methanol = 30: 1) to obtain 1.28 g of a white powder. This white powder was dissolved in ethanol (15 mL), and a solution of 4 M hydrogen chloride in ethyl acetate was added to the resulting solution until the resulting solution had a pH of 1. The precipitates were collected by filtration and recrystallized from 85% ethanol (30 mL), thereby producing 1.06 g of the title compound. Appearance: White powder Melting point: 202-223 ° C Example 2709 Production of 3,4-dichloro-N- maleate. { 6- [4- ( { 2- [4- (2,3-Dihydrobenzo [1,4] dioxin-6-ylmethyl) piperazin-1-yl] -2-oxoethyl.} Methylamino) phenoxy] pyridin-3-yl} benzamide To a solution of ((4- [5- (3,4-dichlorobenzoyl-amino) pyridin-2-yloxy] f-1-yl] -methylamino) acetic acid (2.50 g, 5.6 mmol) in DMF ( 55 mL) was added l- (2, 3-dihydrobenzo [1,4] dioxin-6-imet-1) piperazine (1.7 g, 7.3 mmol), monohydrate of 1-hydroxyben zot ria zol ( 0.86 g, 5.6 mmol) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.29 g, 6.7 mmol) under ice-cooling and the resulting solution it was stirred for 30 minutes under cooling with ice and for 17 hours at room temperature. This reaction solution was concentrated under reduced pressure. Water was added to the residue, and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was dissolved in ethanol (30 mL). Maleic acid (0.32 g, 2.7 mmol) was added to the resulting solution and this solution was allowed to stand. The precipitates were collected by filtration, in order to produce 1.45 g of the title compound. Appearance: Pale yellow powder Melting point: 188-190 ° C Example 2710 Production of N- (6-. {4- [4- (4-benzylpiperazin-1-carbonyl) piperidin-1-yl] phenoxy] pyridin-3-yl) -3,4-dichlorobenzenesulfonamide N- (6- { 4- [4- (4-Benzylpiperazin-1-carbonyl) piperidin-1-yl] phenoxy] pyridin-3-yl) -3,4-dichlorobenzenesulfonamide (0.79 g) was recrystallized from ethanol (15 mL) to yield 0.67 g of the title compound. Appearance: White powder Melting point: 185-189 ° C Example 2711 Production of N- [6- (4-. {[2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4- pyrrol-1-ylbenzamide N- [6- (4- { [2- (4-Piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4 pyrrol-1-ylbenzamide (2.49 g) was recrystallized from a mixed solvent consisting of acetone (20 mL) and diethyl ether (30 mL) to yield 2.26 g of the title compound. Appearance: Pale yellow powder Melting point: 163.1-166.5 ° C Example 2712 Production of N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-fluorophenoxy) pyridin-3-yl] -4- trifluoromethylbenzenesulfonamide N- [6- (4- ([2- (4-Pperoni-piperazin-1-yl) -2-oxoethyl] ethylamino} -2-fluorophenoxy) pyridin-3-yl] -4-trifluoromethyl-benzenesulfonamide (8.18 g) it was recrystallized from a mixed solvent consisting of ethyl acetate (70 mL) and n-hexane (20 mL) to yield 6.93 g of the title compound Appearance: White powder Melting point: 177.8-180.1 ° C Example 2713 Production of 6- (4-. {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl] -2-methylphenoxy} pyridin-3-sulfonyl- (4-trifluoromethylphenyl) amide 6- (4-. {4- [2- (4-Piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl] -2-methylphenoxy}. Pyridin-3 Sulfonyl- (4-trifluoromethylphenyl) amide (1.50 g) was recrystallized from ethanol (20 mL) to yield 1.40 g of the title compound Appearance: White powder Melting point: 156-160 ° C Example 2714 Production of N- [6- (4-. {[2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4- trifluoromethylbenzamide N- [6- (4- { [2- (4-Piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide (2.1 g, 3.2 mmol) was heated to dissolve in acetone (5 mL), and then diethyl ether (10 mL) was added to the resulting solution, whereby recrystallization afforded 2.0 g of the title compound. Appearance: White powder Melting point: 113-116 ° C Example 2715 Production of 3,4-dichloro-N-. { 3-fluoro-4- [4- (1-hydroxy-2-morpholino-4-ylethyl) phenoxy] phenyl} benzamide 3, 4-Dichloro-N- (3-fluoro-4- [4- (l-hydroxy-2-morpholino-4-ylethyl) phenoxy] phenyl] benzamide (5 g) was recrystallized from ethyl acetate- n-hexane to yield 4.73 g of the title compound Appearance: White powder Melting point: 169-170 ° C Example 2716 Production of N- (6-. {4- [4- (4-piperonylpiperazine-1-carbonyl) piperidin-1-carbonyl] phenoxy] pyridin-3-yl) -3,4-dicyrobenzamide A acid solution 1-. { 4- [5- (3,4-dichlorobenzoyl-amino) pyridin-2-yloxy] benzoyl} piperidine-4-carboxylic acid (7.96 g, 15.5 mmol) in DMF (160 mL) were added 1-piperonylpiperazine (3.75 g, 17.6 mmol), 1-hydroxybenzotriazole monohydrate (2.85 g, 18.6 mmol) and l-ethyl hydrochloride 3- (3-dimethylaminopropyl) -carbodiimide (3.56 g, 18.6 mmol) under cooling with ice, and the resulting solution was stirred overnight at room temperature. This reaction solution was concentrated under reduced pressure. To the residue, water and ethyl acetate were added and the resulting solution was stirred vigorously. The [224 Resulting precipitates were collected by filtration and recrystallized from a dichloromethane-methanol mixed solvent, to thereby yield 7.36 g of the title compound. Appearance: White powder Melting point: 236-238 ° C Example 2717 Production of N-. { 6- [(4- { 4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl}. Phenyl) methylamino] -pyridin-3-yl] -4- trifluoromethylbenzamide To a solution of [1- (4. {methyl (5- (4-trifluoromethylbenzoylamino) pyridin-2-yl] amino} phenyl) piperidin-4-yl] acetic acid (0.80 g, 1.6 mmol) DMF (10 mL) was added with 1-piperonylpiperazine (0.41 g, 1.9 mmol), 1-hydroxybenzotriazole monohydrate (0.24 g, 1.6 mmol) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.39 g, 2.0 mmol) under cooling with ice, and the resulting solution was stirred for 3 hours at room temperature. This reaction solution was concentrated under reduced pressure. To the residue was added a saturated sodium bicarbonate solution, and extracted with dichloromethane. The dichloromethane layer was washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by chromatography in column on silica gel (dichloromethane: methanol = 20: 1). The resulting product was then recrystallized from a mixed solvent consisting of 95% ethanol-dichloromethane, thereby yielding 1.05 g of the title compound. Appearance: White powder Melting point: 210-212 ° C Formulation Example 1 100 g of N- [6- (4- {4- [2- (piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} were mixed and milled together. phenoxy) pyridin-3-yl] -4-trif luoromet i lbenzamide obtained in Example 319, 40 g of Avicel (trade name, manufactured by Asahi Kasei Corporation), 30 g of corn starch and 2 g of magnesium stearate. The resulting mixture was then formed as a 10 mm R-coated sugar tablet using a pestle. The obtained tablets were coated with a film coating agent containing 10 g of TC-5 (trade name, manufactured by Shin-Etsu Chemical Co., Ltd., hydroxypropylmethylcellulose), 3 g of polyethylene glycol 6000, 40 g of crude oil. castor and a suitable amount of ethanol, for this prepare a film coated tablet.

Pharmacological test 1 Anticancer effect (in vi tro) on cancer cells The anti-proliferative effect of the test compounds on human liver cancer cells (HuH-7), human lung cancer cells (EBC-1), cancer cells human colorectal cancer (HCT116), human prostate cancer cells (22Rvl), human pancreatic cancer cells (MIA PaCa-2), human stomach cancer cells (MKN45), human breast cancer cells (ZR-75-1) was reviewed by a method of sulforhodamine B according to S ehan P et al. (J. Nati, Cancer Inst. 1990 Jul 4; 82 (13). 1107-12). An explanation will be given by taking HuH-7 cells as an example. HuH-7 cells were seeded in DMEM medium (Dulbeco's Modified Eagle Medium) containing 10% fetal bovine serum from a 96-well microplate and cultured at 37 ° C for 24 hours in the presence of 5% carbon dioxide gas. % (C02). Subsequently, a test compound was added to the wells and the cells were cultured for a further 5 days. After cultivation, trichloroacetic acid was added to the wells to thereby obtain a final concentration of 10%. The microplate was allowed to stand fixed at 4 ° C for one hour to fix the cells on the wells. The microplate was washed with water to remove the medium and trichloroacetic acid and dried in air. After drying in air, the microplate was stored at 4 ° C until it was stained with sulforrodamine B. To each of the wells was added an aqueous solution of 1% acetic acid containing 0.4% sulforhodamine B and the wells were allowed to stand fixed at room temperature for 20 to 30 minutes. After removing the supernatant, each well was washed with the aqueous solution of 1% acetic acid and an aqueous solution of Tris (Tris hydroxyaminomethane) 10 mM was added to each well and shaken. In this way, the dye absorbed in the cell was eluted. Subsequently, the OD (optical density) was measured at a measurement wavelength of 492 nm and a reference wavelength of 690 nm to obtain the difference (A) in OD measured in this way. In addition, the OD of a control well (which did not contain cells) was measured at a measurement wavelength of 492 nm and a reference wavelength of 690 nm to obtain the difference (B) in OD. The difference (A-B) was considered as the cell proliferation activity of each of the wells. The anti-proliferative effect of the test compounds in human chronic myelogenous leukemia cells (KU812) was determined by an MTT assay according to the method described in Singh AK et al. (Cancer Lett, 1996 Oct 1; 107 (1), 109-15). To describe it more specifically, KU812 cells were seeded in RPMl 1640 medium containing 10% fetal bovine serum from a 96-well microplate, cultured at 37 ° C for 24 hours in the presence of a 5% carbon dioxide gas (C02). Subsequently, a test compound was added to the wells and the cells were cultured for a further 5 days. After the incubation, 10 μl of 5 mg / mL of MTT (3- (4,5-dimethyl) -2,5-diphenyltetrazolium bromide) was added to the wells. After the cells were cultured for four hours, 100 μl of 0.01N HCl containing 10% SDS (sodium dodecyl sulfate) were added to the wells, which was further cultivated overnight. Subsequently, the OD was measured at a measurement wavelength of 570 nm and a reference wavelength of 690 nm to obtain the difference (A) in OD. In addition, the OD of a control well (which did not contain cells) was measured at a measurement wavelength of 570 nm and a reference wavelength of 690 nm to obtain the difference (B) in OD. The difference (A-B) was considered as the cell proliferation activity of each of the wells. The cell proliferation activity (T) at the time a test compound was added was compared to the control (C) (which contained test compound) and the cell proliferation suppression activity (T / C) of the Test compound was obtained computationally. Based on this, the concentration (IC 50) of the test compound at which the proliferation of 50% of the cells was inhibited, ie the concentration of the test compound, was obtained. which provides T / C = 0.5 [Table 432] Pharmacological test 2 Anticancer effect (in vi tro) on liver cancer cells HuH-7 Human liver cancer cells HuH-7 were transplanted into SCID mice (a group of 6 female mice).

The antitumor effect of the test compounds according to the present invention was reviewed. To describe more specifically, cancer cells were cultured by A cell suspension solution containing cancer cells at a concentration of 2.5 x 10 7 cells / mL was prepared. Then, 0.2 mL of the cell suspension solution was injected into the right axillary region of each of the mice to transplant the cancer cells. In this way, mice carrying cancer were prepared. When the tumor grew to a diameter of 5 mm or more, the mice were divided into groups based on tumor volume. From the next day after the pooling, a suspension solution of 5% gum arabic containing test compound was administered orally once a day for 9 consecutive days. A suspension solution of 5% gum arabic was administered to a control group. The next day after concluding the administration, the volume of a tumor was measured. The volume ratio of a tumor at the time of grouping in relation to that measurement the following day after the end of administration was calculated to obtain a relative tumor volume of each group. The ratio (T / C%) in the relative tumor volume of a control group to a test group (administered with a test compound) was then calculated and used as an index of the effect. The relative tumor volume = tumor volume measured the day after the administration / tumor volume at the time of the termination.

(T / C%) = (average value of relative tumor volume of test compound administration group) / (average value of relative tumor volume of a control group) x 100. [Table 433] Pharmacological test 3 The anti-proliferative effect of the test compounds in human renal cancer cells (Caki-2) was reviewed in the same way as in pharmacological test 1 according to the method of sulforhodamine B of Skehan P et al. In addition, the anti-proliferative effect of the test compounds in human acute myelogenous leukemia (KG-1) cells, human Burkitt's lymphoma cells (Daudi), human lymphoma cells (U937) and human multiple myeloma cells (IM) -9) was revised by the MTT assay in the same way as the pharmacological test 1 according to Singh AK et al. (Cancer Lett, 1996 Oct 1; 107 (1), 109-15). The IC50 values of human renal cancer cells (Caki-2), human acute myelogenous leukemia (KG-1) cells and human multiple myeloma cells (IM-9) are shown in Table 434. The cell proliferation activity of each of the test compounds in cells of human Burkitt's lymphoma (Daudi) (and human lymphoma cells (U937) was compared to that of a control (which did not contain test compounds) to obtain cell proliferation suppression (T / C) activities of each test compound The results are shown in table 435. [Table 434] [Table 435] It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (1)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. An antitumor agent characterized in that it comprises a compound represented by the general formula (1) below, or a salt thereof as an active ingredient: [ Formula 1] wherein Xi represents a nitrogen atom or a group -CH =, Ri represents a group -Z-R6, Z represents a group -N (R8) -B-, a group -BN (R8) -, a group -B0 -OR-, a group [Formula 2] -NHCO- S a group -CO-, a group -CH (OH) -, a group -N (R9a) -CO-N- (R9b) -, a group -N = CH-, a group -N (R10a) -S02- (B22a) e-, a lower alkenylene group, a -NHCO-Bi- group, a -NHC0-B2- (W) u- group, a -Bo-0-B? Ga- group, a group [Formula 3] , , a group [Formula 4] / \ -N N- (B2ia) c- , a group -S02-N (R10b) -, a group -S-, a lower alkynylene group, a lower alkylene group, a group -N (R8d) - or a group -CO-NH-Bißa-, R8 represents a hydrogen atom, a lower alkyl group which may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a lower alkyl phenyl group, B represents a -CO- group or a lower alkylene group, B0 represents a lower alkylene group, Bi represents a lower alkenylene group which may have a phenyl group as a substituent, B2 represents a lower alkylene group which may be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group, Rga represents a hydrogen atom or a lower alkyl group, Rgb represents a hydrogen atom or a lower alkyl group, Rioa represents a hydrogen atom or a lower alkyl group, B22a represents a lower alkylene group or a lower alkenylene group, e represents 0 or 1, Bisa represents a lower alkylene group, B ? 9a represents a lower alkylene group, B2oa represents a lower alkylene group, B2? Represents a lower alkylene group, k represents 2 or 3, c represents 0 or 1, d 'represents 0 or 1, Riob represents a hydrogen atom or a lower alkyl group, Rsd represents a hydrogen atom or a lower alkyl group, represents an oxygen atom, a group -NH-, or a sulfur atom, u represents 0 or 1, Rd represents a heterocyclic group of 5 to 15 monocyclic, dicyclic or tricyclic saturated or unsaturated members having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (which may have 1 to 3) substituents, which are selected from the group consisting of an oxo group; a lower alkoxy group which may have a halogen atom as a substituent; a lower alkyl group which may have a halogen atom as a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group which may be substituted by a lower alkyl group which may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantyl group, a naphthyl group (which may have 1 to 3 groups selected of the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), a alkyl group which may have a lower alkoxy group as a substituent, a cycloalkyl group which may be substituted by a group selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may be have a halogen atom as a substituent, in the cycloalkyl ring, a lower alkenyl group which may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkyl group which may have a halogen atom and an atom of halogen, as a substituent, on the phenyl ring), a lower alkyl group substituted with halogen atom, cycloalkyl lower alkyl group or a group [Formula 5] R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group which may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group , a cyano group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a saturated or unsaturated 5- or 6-membered heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (which may have an oxo group in the heterocyclic ring), m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R7s can be identical or different) and R2 represents a hydrogen atom, a halogen atom, or a lower alkyl group, Y represents a group -O- , a group -N (R5) -, a group -CO-, a group -CH (OH) -, a lower alkylene group, a group -S (0) n-, or a group -C (= N-0H ) -, R5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group, n represents 0, 1 or 2, A represents a group [Formula 6 ] , or a group [Formula 7] p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a - CONRuR12, or a cyano group, wherein R11 and R12 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R11 and R12, together with the nitrogen to which they are attached may be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to fuse a saturated 5- to 7-membered heterocyclic ring, R4 represents a lower alkyl imidazolyl group, a 1,2-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1, 2, 5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have a group oxo as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group which may have an alkyl group lower as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 8] , a group [Formula 9] or a group; t)? - N (R14) R15, R, 113J represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group , a lower alkanoyl group substituted with morpholino, a piperazinyl carbonyl lower alkyl group which may be substituted, in the piperazine ring, by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkyl group which may be substituted, on the piperazine ring, by an alkyl phenyl group which lower alkyl can have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl group substituted with morpholinocarbonyl, or a lower alkanoyl imidazolyl group, R13a represents a hydrogen atom or a hydroxyl group, T represents a lower alkylene group, a group -N (R17) -B3-CO-, a group -B19-N (R18) -CO-, a group -B4-CO-, a group -Q-B5-CO-, a group -B6-N ( R19) -B7-CO-, a group -CO-B8-, a group -CH (OH) -B9-, a group -CO-B10-CO-, a group -CH (OH) - Bn-CO-, a group -CO-, a group -S02-, or a group -B23a-CO-CO-, wherein R17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a group for lower alkanoyl which may have a halogen atom as a substituent, a lower alkenyl group, an amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group, B3 represents a lower alkylene group, B19 represents a lower alkylene group, Rie represents a hydrogen atom or a lower alkyl group, B represents a lower alkenylene group or a lower alkylene group which may have a hydroxyl group as a substituent, Q represents an oxygen atom or a group -S (0) n- ( wherein n is equal to that described above), B5 represents a lower alkylene group, Be represents a lower alkylene group, R19 represents a hydrogen atom or a lower alkanoyl group, B7 represents a lower alkylene group, B8 represents a lower alkylene group, B9 represents a lower alkylene group, Bio represents a lower alkylene group, Bu represents a lower alkylene group, B23a represents a lower alkylene group, 1 represents 0 or 1, R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents (2) an alkyl group substituted with a hydroxyl group, (3) a cycloalkyl group which may have a group selected from the group consisting of a group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; a lower alkoxy amino group which may have a lower alkyl group as a substituent; a lower alkyl group substituted with a hydroxyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group having a group lower alkylenedioxy as a substituent on the phenyl ring, (10) a lower alkyl group substituted with lower alkoxycarbonyl, (11) a lower alkyl group substituted with carboxy, (12) an amino group which may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group which may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent (s) on the tetrahydroquinoline ring, (14) a lower alkyl cycloalkyl group, (15) a lower alkyl piperazinyl group which can be substituted, in the piperazine ring, by a phenyl lower alkyl group which can have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a lower alkyl pyridyl group, (17) a lower alkyl group substituted with a amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkyl lower alkoxy group, (19) an imidazolyl group, (20) an imide group azolyl lower alkyl, (21) a lower alkyl group substituted with 1,2,3,4-tetrahydroisoquinolylcarbonyl, (22) a piperidinylcarbonyl group which may have a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group , and a furilo alkyl group lower as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group which may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a lower alkyl furyl group, (25) a lower alkyl carbonyl group substituted by a group [Formula 10] , (26) a lower alkyl carbonyl group substituted by a group [Formula 11] (27) a group -CO-B20-N (R36) R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a lower alkyl morpholino group, (28a) a lower alkenyl phenyl group, (29a) an anilinocarbonyl alkyl group lower one which may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) an alkyl piperazinyl group which may have, as a substituent on the piperazine ring, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group which may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group which may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group which may have a lower alkyl group as a substituent, (36a) an oxalyl group substituted with piperazinyl which may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (which may have 1 to 3 groups selected of the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent (s) on the phenyl ring) and a lower alkyl pyridyl group as a substituent (s) in the piperazine ring, or (37a) a lower alkyl group substituted with cyano, R34 represents an oxo group or a phenyl group, d represents an integer from 0 to 3, B2o represents a lower alkylene group, R36 and R37, together with the nitrogen atom to which they are attached can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom 124 to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups which may have a lower alkylenedioxy group in the phenyl ring, may be present as a substituent (s), R 14 and R15, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5-10 membered heterocyclic ring or unsaturated; or a group [Formula 12] wherein, in the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a lower alkyl group substituted with phenyl, having 1 to 2 phenyl groups which may be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, an atom of halogen, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenolio lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, and which may have a pyridyl group in the lower alkyl group, (29) a carbamoyl group, (30) a group pyridyl lower alkyl which may have, as a substituent (s) on the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a lower alkyl benzothiazolyl group, (34) ) a furyl lower alkyl group, (35) a benzoyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group which can have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene group lower alkyl which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a piperazinyl group, (38) a pyridyl group, (39) n group lower alkoxycarbonyl, (40) a thiazolidinyl lower alkyl group which may be substituted, on the thiazolidine ring, by a group selected from the group consisting of an oxo group and a group [Formula 13] Ra = N-N = (Rb (wherein Ra and Rb each represents a lower alkyl group), (41) a lower alkyl group which may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a group lower alkanoyl which may have a halogen atom as a substituent, (43) a phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group which may have a lower alkylenedioxy group as a substituent on the ring phenyl, (45) a naphthyl lower alkyl group, (46) a phenoxy group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which can have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a n substituent, (49) a group - (B12C0) tN (R20) R21, (50) a group - (CO) or B? 3-N (R22) R23, (51) a lower alkyl group substituted with 1, 2, 3,4-tetrahydronaphthyl which can be substituted, on the 1, 2, 3, 4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent (s), (52) a cycloalkyl group which can have a hydroxyl group as a substituent, (53) a piperidinyl group that can be substituted, in the piperidine ring, by 1 to 3 groups lower alkyl as a substituent (s), (54) a lower alkyl quinolyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group which may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring, (57) a lower alkyl benzoyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent (s) on the phenyl ring, (58) a lower alkyl piperidinyl group which may have a lower alkyl group as a substituent on the ring piperidine, (59) an imidazolyl group which may have 1 to 3 phenyl groups as a substituent (s) in the imidazole ring, (60) a benzimidazolyl group which may have 1 to 3 lower alkyl groups as a substituent (s) in the ring of benzimidazole, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a group 1, 3,4-oxadiazolyl lower alkyl which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, (64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl group lower alkyl, (67) a pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1, 2, 3, 4-tetrahydroquinolylcarbonyl group which may have one group oxo as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) a lower alkanoyl imidazolyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, ( 82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group - (0-B15) s-CO-N (R26) R27, (85) a group -N (R28) - CO-B? 6-N (R29) R30, (86) a group -N (R31) -B17-CO-N (R32) R33, (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, Bi2 represents a lower alkylene group, t represents 0 or 1, R20 and R21 may be identical or different and each represents a hydrogen atom; an amino group which may have a lower alkoxycarbonyl group as a substituent; a benzoyl group that can have 1 to 3 lower alkoxy groups 1 4 as a substituent (s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group which may be substituted, on the phenyl ring, by the 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group which may have 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent on the pyrrolidine ring; • a lower alkyl group substituted with amino which may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as a substituent (s) on the 1, 2, 3, 4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; an alkyl pyridyl group lower; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent (s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group; a phenoxy lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent (s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group which may have a halogen atom as a substituent; a lower alkanoyl imidazolyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a lower alkyl carboxy group, or a cycloalkyl group; and R20 and R21, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 7. members (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group which may have 1 to 3 groups selected from the group consisting of one atom of halogen and a lower alkyl group that can having a halogen atom as a substituent (s) on the phenyl ring, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), or represents 0 or 1, B13 represents a lower alkylene group , R22 'and R23 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring, a phenoxy group lower alkyl which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R22 and R23, together with the nitrogen atom to which they are attached, may be attached to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), B15 represents a lower alkylene group, s represents 0 or 1, R26 and R27 may be identical or different and each one represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or a lower alkyl imidazolyl group, and R2d and R27, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, (wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups may have a lower alkylenedioxy group as a substituent, they may be present on the phenyl ring, as a substituent (s)), R28 represents a hydrogen atom or a lower alkyl group, Bi6 represents a lower alkylene group, R29 and R30, together with the nitrogen atom at which they join, they can bind to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, where, in the heterocyclic ring lico, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, R31 represents a hydrogen atom or a group lower alkyl, B17 represents a lower alkylene group, R32 and R33, together with the nitrogen atom to which they are attached, can be attached to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom for form a saturated 5- to 7-membered heterocyclic group, (where, in the heterocyclic ring, they may be present 1 to 3 substituents, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), as long as the compound mentioned above or a salt thereof satisfies the following requirements (i) to (v): (i) when Xi represents a group -CH =, then R3 represents a hydrogen atom; (ii) when Xi represents a group -CH =, 1 represents 1, T represents -CO-, and R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents the group (24); (iii) when Xx represents a group -CH =, 1 represents 1, and T represents -N (R17) -B3-CO-, R14 and R15, together with the nitrogen atom to which they are attached, can bind to each other , directly or through a nitrogen atom, Oxygen atom, or sulfur atom to form a saturated or unsaturated 5- to 10-membered heterocyclic ring, wherein, in the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent (s); (iv) when Xi represents a nitrogen atom, and 1 represents 0, or when Xx represents a nitrogen atom, 1 represents 1, and T represents -CO- or -S02, R15 is not a group (5), (7) ), (19), or (20); and (v) when R6 represents a cycloalkyl group which may have on the cycloalkyl ring, a substituent selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have one atom of halogen as a substituent, R4 represents a group - (T) iN (R14) R15 (wherein T and 1 are the same as those described above, and R14 and R15, together with the nitrogen atom to which they are attached, can bind one to the other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5-10 members, or R14 and R15 form a group [Formula 14] The antitumor agent in accordance with claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-1) to (1-7) below or a salt thereof, an active ingredient: [Formula 15] -TO (1-1) (1-2) (1-3) (1-4) (1-5) (1-6) (1-7) wherein Y3 represents a lower alkylene group. 3. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-8) to (1-14) below or a misrao salt as an active ingredient: [Formula 16] (1- (1-9) (1-10) (1-11) (1-12) (1-13) (1-14) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-15) to (1-21) below or a salt thereof as an ingredient active: [Formula 17] -TO (1-15) (1-16) (1-17) (1-18) (1-19) (1-20) (1-21) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-22) to (1-28) below or a salt thereof as an ingredient active: [Formula 18] -TO (1-22) (1-23) (1-24) "-TO (1-25) (1-26) (1-27) (1-28) wherein Y3 represents a lower alkylene group. 6. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-29) to (1-35) below or a salt of the misrao as an ingredient active: 12 4 [Formula 19] -TO (1-29) (1-30) (1-31) n - A (1-32) (1-33) (1 -34) (1-35) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-36) to (1-42) below or a salt thereof as an ingredient active: [Formula 20] (1-36) (1-37) (1-38) (1-39) (1-40) (1-41) (1 -42) wherein Y3 represents a lower alkylene group. 8. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-43) to (1-49) below or a salt thereof as an ingredient. active: [Formula 21] TO (1-43) (1-44) (1-45) (1-46) (1-47) (1-48) (1-49) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-50) to (1-56) below or a salt thereof as an ingredient active: [Formula 22] (1-50) (1-51) (1 ^ 52) (1-53) (1-54) (1-55) (1-56) wherein Y3 represents a lower alkylene group. 10. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-57) to (1-63) below or a salt thereof as an ingredient active: [Formula 23] -57) (1-58) (1-59) (1-60) (1-61) (1-62) (1-63) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-64) to (1-70) below or a salt thereof as an ingredient active: [Formula 24] -TO (1-64) (1-65) (1-66) (1-67) (1-68) (1-69) (1-70) wherein Y3 represents a lower alkylene group, and Zi represents a lower alkenylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-71) to (1-77) below or a salt thereof as an ingredient active: [Fórmu la 2 5 ^ (1-71) (1-72) (1-73) n-A (1-74) (1-75) (1-76) (1-77) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-78) to (1-84) below or a salt thereof as an ingredient active: [Formula 26] (1-78) (1-79) (1-80) R6- (W) (1-81) (1-82) (1-83) (1-84) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-85) to (1-91) below or a salt thereof as an ingredient active: [Fórmu l a 27] (1-85) (1-86) (1-87) (1- (1-89) (1-90) (1-91) wherein Y3 represents a lower alkylene group. 15. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-92) to (1-98) below or a salt thereof as a active ingredient: [Formula 28] (1-95) (1-96) (1-97) (1-98) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-99) to (1-105) below or a salt thereof as an ingredient active: [Formula 29] (1-99) (1-100) (1-101) (1-105) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-106) to (1-112) below or a salt thereof as an ingredient active: [Formula 30] (1-106) (1-107) (1-108) (1-109) (1-110) (1-111) (1-112) wherein Y3 represents a lower alkylene group. 18. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-113) to (1-119) below or a salt thereof as an ingredient. active: [Formula 31] TO (1-113) (1-114) (1-115) (1-116) (1-117) (1-118) (1-119) wherein Y3 represents a lower alkylene group. 19. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-120) to (1-126) below or a salt thereof as an ingredient. active: [Formula 32] (1-120) (1-121) (1-122) (1-123) (1-124) (1-125) (1-126) wherein Y3 represents a lower alkylene group, and Z2 represents a lower alkynylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-127) to (1-133) below or a salt thereof as an ingredient active: 127 1 [Formula 33] (1-127) (1-128) (1-129) (1-130) (1-131) (1-132) (1-133) wherein Y3 represents a lower alkylene group. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-134) to (1-140) below or a salt thereof as an ingredient active: [Formula 34; (1-134) (1-135) (1-136) (1-137) (1-138) (1-139) (1-140) wherein Y3 represents a lower alkylene group, and Z3 represents a lower alkylene group or a -N (Rd) - group. 22. The antitumor agent according to any of claims 1 to 21, characterized in that Y is a group -O-. 23. The antitumor agent according to any of claims 1 to 21, characterized in that Y is a group -N (R5) -. 24. The antitumor agent according to any of claims 1 to 21, characterized because Y is a group -CO-, a group -CH (OH) -, a lower alkylene group, a -S (0) n- group, or a -C (= N-OH) - group. 25. The antitumor agent according to any of claims 1 to 21, characterized in that A is a group [Formula 35] 26. The antitumor agent according to any of claims 1 to 21, characterized in that A is a group [Formula 36] 27. The antitumor agent according to any of claims 1 to 21, characterized in that R4 represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a group 1, 2, 5-triazolyl lower alkyl, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a group 1,2,4- oxadiazolyl lower alkyl which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 37 ] or a group [Formula 38] 28. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T)? -N (R14) R15, and 1 is 0. 29. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) XN (R14) R15, and 1 is 1. 30. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) iN (R14) R15, 1 is 1, and T is a group -N (R17) -B3-CO-. 31. The antitumor agent according to any of claims 1 to 21, characterized because R is a group - (T)? - N (R) R, 1 is 1, and T is a group -B? 9-N (R18) -C0-. 32. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) -N (R14) R15, 1 is 1, and T is a group -B4-CO-. 33. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) X-N (R14) R15, 1 is 1, and T is a group -Q-B5-CO-. 34. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) iN (R14) R15, 1 is 1, and T is a group -B6-N (R19) -B7 -. 35. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T)? ~ N (R14) R15, 1 is 1, and T is a group -CO-B8-. 36. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a group -CH (OH) -B9-. 37. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a group - 1 CO-Bio-CO-. 38. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) iN (R14) R15, 1 is 1, and T is a group -CH (OH) -Bn-CO -. 39. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) i-N (R14) R15, 1 is 1, and T is a -C0- group. 40. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T)? -N (R14) R15, 1 is 1, and T is a group - S02-. 41. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T)? -N (R14) R15, 1 is 1, and T is a group -B23a-CO-CO- . 42. The antitumor agent according to any of claims 1 to 21, characterized in that R4 is a group - (T) X-N (R14) R15, 1 is 1, and T is a lower alkylene group. 43. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of the compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1 -58), (1-64) and (1-65) or a salt thereof as an active ingredient, wherein Y is a group -O- or a group -N (R5) -, A is a group [Formula 39] R4 is a group - (T) i-N (R14) R15. 44. The antitumor agent according to claim 43, characterized in that 1 is 1, and T is a group -N (R17) -B3-CO-. 45. The antitumor agent according to claim 43, characterized in that 1 is 1, and T is a -B4-CO- group. 46. The antitumor agent according to claim 43, characterized in that 1 is 1, and T is a -CO- group. 47. The antitumor agent according to claim 43, characterized in that 1 is 0. 48. The antitumor agent according to claim 1, characterized in that it comprises a compound selected from the group consisting of N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-methoxyphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} phenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- ([2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino] -2-fluorophenoxy) pyridine 3-yl] -4-trifluoromethylbenzamide, N- [6- (4. {[2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-fluorophenoxy) pyridin-3 il] -4-trifluoromethylbenzamide, N- [6- (4. {[2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino] -2-methoxyphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-methoxyphenoxy) pyridin-3-yl] -4 -trifluoromethylbenzamide, N- [6- (4- ([2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] ethylamino} -2-methylphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide , N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N - (6- { 4- [3- (4-piperoniIpiperazin-1-yl) -3-oxopropyl] phenoxy] pyridin-3-yl) -3,4-dichlorobenzenesulfonamide, N- [6- (4 - (4- [2- (4-piperonylpiperazin-1-yl) -2-oxo ethyl] piperazin-l-il} phenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4-. {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl}. phenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N-. { 6- [(4- { 4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} phenyl) methylamino] pyridin-3-yl} -4-trifluoromethylbenzamide, N- [6- (4-. {4- [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridine 3-yl] -4-trifluoromethylbenzamide, N- [6- (4- { 4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin- "3-yl] -4 -trifluoromethylbenzamide, N- [6- (4-. {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methylphenoxy) pyridin-3 il] -3,4-dichlorobenzamide, N- { 6- [4- (4-benzylpiperazin-1-carbonyl) phenoxy] pyridin-3-yl.} -4-trifluoromethylbenzamide, N-. [4- (4-benzylpiperazine-1-carbonyl) phenoxy] pyridin-3-yl.} - 3, 4-dichlorobenzamide, N- [6- (. {4- [3- (4-piperonylpiperazine-1) il) -3-oxopropyl] phenyl.} methylamino) pyridin-3-yl] -4-trifluoromethylbenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2- oxoethyl] ethylamino.} -2-fluorophenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2- oxoethyl] methylamino.} -2-fluorophenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2- oxoethyl] methylamino.} -2-methoxyphenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, N- [6- (4 -. { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} phenoxy) pyridin-3-yl] -3,4-dichlorobenzamide, 1- (6-. {4- [3- (4-piperonylpiperazin-1-yl) -3-oxopropyl] phenoxy] pyridin-3 il) -3- (3,4-dichlorophenyl) -1-ethylurea, N- (6-. {4- [3- (4-piperonylpiperazin-1-yl) -3-oxopropyl] phenoxy] pyridine 3-yl) -4-trifluoromethylbenzamide, N- [6- (4. {[2- (4-benzylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3 il] -4-trifluororaethyl-phenylbenzamide, N- [6- (4-. {4- [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} phenoxy) pyridin-3 -yl] -3,4-dichlorobenzamide, N- (6- { 4- [3- (4- piperonylpiperazine-1-carbonyl) piperidin-1-yl] phenoxy} pyridin-3-yl) -3,4-dichlorobenzamide, N- [6- (4-. {4- [2- (4-benzyl-piperazin-1-yl) -2-oxoethyl] piperidin-1-yl}. phenoxy) pyridin-3-yl] -4-trifluoromethylbenzamide, N-. { 6 - [(4- {4- [2- (4-benzylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} phenyl) methylamino] pyridin-3-yl} -4-trifluoromethylbenzamide, N- (6- { 4- [(2- {4- [4- (4-fluorobenzoyl) phenyl] piperazin-1-yl} -2-oxoethyl) methylamino] - 2-methoxyphenoxy, pyridin-3-yl) -4-trifluoromethylbenzamide, 2- (4-piperonylpiperazin-1-yl) -N-. { 3-methyl-4- [5- (4-trifluoromethylphenoxymethyl) iridin-2-yloxy] phenyl} -2-oxoacetamide, N- [6- (4- { [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] methylamino} -2-methylphenoxy) pyridin-3-yl] -2 -fluoro-4-trifluoromethylbenzamide, N- [6- (4-. {4- [2- (4-piperonylpiperazin-1-yl) -2-oxoethyl] piperidin-1-yl} -2-methoxyphenoxy) iridin-3-yl] -4-trifluoromethylbenzamide and 4- (3. {3-methyl-4- [5- (4-trifluoromethylbenzoylamino) iridin-2-yloxy] phenyl} -2-- ethyl ester. oxohexahydropyrimidin-1-yl) benzoic acid, or a salt thereof as an active ingredient. 49. The antitumor agent according to any of claims 1 to 48, characterized in that one target of the antitumor agent is a malignant tumor. 50. The antitumor agent according to claim 49, characterized in that the malignant tumor is a solid tumor. 51. The antitumor agent in accordance with claim 49, characterized in that the rasaignal tumor is a hematologic cancer. 52. The antitumor agent according to claim 49, characterized in that the malignant tumor is lymphoma, leukemia, or myeloma. 53. A method for treating or preventing tumors, characterized in that it comprises the administration of a compound represented by the general formula (1) below or a salt thereof: [Formula 40] wherein Xi represents a nitrogen atom or a group -CH =, R1 represents a group -Z-R6, Z represents a group -N (R8) -B-, a group -BN (R8) -, a group -B0 -OR-, a group [Formula 41] - -NMuHrCnO _ a group -CO-, a group -CH (OH) -, a group -N (R9a) -CO-N- (R9b) -, a group -N = CH-, a group -N (R10a) -S02- (B22a) e-, a lower alkenylene group, a group -NHCO-Bi-, a group -NHCO-B2- (W) u-, a group -BO-0-B? 9a-, a group [Formula 42] d ' , a group [Formula 43] -N N- (B21a) c- , a -S02-N (R10b) -, a -S- group, a lower alkynylene group, a lower alkylene group, a -N (R8d) - or a -CO-NH-Bisa-R8 group represents a hydrogen atom, a lower alkyl group which may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a lower alkyl phenyl group, B represents a -CO- group or a lower alkylene group, Bo represents a lower alkylene group, Bi represents a lower alkenylene group which may have a phenyl group as a substituent, B2 represents a lower alkylene group which may be substituted by a group selected from the group consisting of a lower alkoxy group and a phenyl group, R9a represents a hydrogen atom or a lower alkyl group, R9b represents a hydrogen atom or a lower alkyl group, R10a represents a hydrogen atom or a lower alkyl group, B22a represents a lower alkylene group or a lower alkenylene group, e represents 0 or 1, Bisa represents a lower alkylene group, Bi9a represents a lower alkylene group, B2oa represents a lower alkylene group, B2ia represents a lower alkylene group, k represents 2 or 3, c represents 0 or 1, d1 represents 0 or 1, R10b represents a hydrogen atom or a lower alkyl group, R8d represents a hydrogen atom or a lower alkyl group, represents an oxygen atom, a group -NH-, or a sulfur atom, u represents 0 or 1, R6 represents a heterocyclic group of 5 to 15 membered monocyclic, dicyclic or tricyclic saturated or unsaturated having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms (which may have 1 to 3 substituents, which are selected from the group consisting of an oxo group); a lower alkoxy group which may have a halogen atom as a substituent; a lower alkyl group which may have a halogen atom as a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group which may be substituted by a lower alkyl group which may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantyl group, a naphthyl group (which may have 1 to 3 groups selected of the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), a alkyl group which may have a lower alkoxy group as a substituent, a cycloalkyl group which may be substituted by a group selected from the group consisting of a lower alkyl group substituted with amino which may have an alkyl group lower and a lower alkyl group which may have a halogen atom as a substituent, in the cycloalkyl ring, a lower alkenyl group which may have a halogen atom as a substituent, a lower alkanoyl group, a benzoyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkyl group which may have a halogen atom and halogen atom, as a substituent, on the phenyl ring), a lower alkyl group substituted with halogen atom, cycloalkyl lower alkyl group or a group [Formula 44] R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group which may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group , a cyano group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a saturated or unsaturated 5- or 6-membered heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (which may have an oxo group in the heterocyclic ring), m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R7s may be identical or different) and R2 represents a hydrogen atom, a halogen atom, or a lower alkyl group, Y represents a group -O-, a group -N (R5) -, a group -CO-, a group -CH (OH) -, a lower alkylene group, a group -S (0) n-, or a group -C (= N-OH) -, R5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group, n represents 0, 1 or 2, A represents a group [Formula 45] or a group [Formula 46] p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a group - CONRnR12, or a cyano group, wherein R11 and R12 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R1L and R12, together with the nitrogen to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, R4 represents a lower alkyl imidazolyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have a group oxo as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group which may have an alkyl group lower as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 47] , a group [Formula 48] or a group - (T) X-N (R14) R15, R > 113J represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, an imidazolyl lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a carboxy lower alkyl group, a benzoyl group, a lower alkanoyl group substituted with morpholino, a piperazinyl carbonyl lower alkyl group which can be substituted, in the piperazine ring, by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a piperazinyl lower alkyl group which may be substituted, on the piperazine ring, by an alkyl phenyl group which lower alkyl can have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl group substituted with morpholinocarbonyl, or a lower alkanoyl imidazolyl group, R13a represents a hydrogen atom or a hydroxyl group, T represents a lower alkylene group, a group -N (R17) -B3-CO-, a group -Bi9-N (R18) -CO-, a group -B4-CO-, a group -Q-B5-CO-, a group -B6-N ( R19) -B7-CO-, a group -CO-B8-, a group -CH (0H) -B9-, a group -CO-B10-CO-, a group -CH (OH) -B11-CO-, a group -CO-, a group -S02-, or a group -B23a-CO-CO-, wherein R17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a a lower alkanoyl which may have a halogen atom as a substituent, a lower alkenyl group, an amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent, or a lower alkylsulfonyl group, B3 represents a lower alkylene group, B19 represents a lower alkylene group, R18 represents a hydrogen atom or a lower alkyl group, B4 represents a lower alkenylene group or a lower alkylene group which may have a hydroxyl group as a substituent, Q represents an oxygen atom or a group -S (0) n- ( wherein n is equal to that described above), B5 represents a lower alkylene group, Be represents a lower alkylene group, R19 represents a hydrogen atom or a lower alkanoyl group, B7 represents a lower alkylene group, B8 represents a lower alkylene group, B9 represents a lower alkylene group, Bio represents a lower alkylene group, Bu represents a lower alkylene group, B23a represents a lower alkylene group, 1 represents 0 or 1, R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents (2) an alkyl group substituted with a hydroxyl group, (3) a cycloalkyl group which may have a group selected from group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; a lower alkoxy amino group which may have a lower alkyl group as a substituent; a lower alkyl group substituted with a hydroxyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group, or a substituent on the piperazine ring; a pyrrolidinyl group which may have an oxo-corao group a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group having a group lower alkylenedioxy as a substituent on the phenyl ring, (10) a lower alkyl group substituted with lower alkoxycarbonyl, (11) a lower alkyl group substituted with carboxy, (12) an amino group which may have a lower alkanoyl group as a substituent, (13) a 1,2,3,4-tetrahydroquinolyl group which may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent (s) on the tetrahydroquinoline ring, (14) a lower alkyl cycloalkyl group, (15) a lower alkyl piperazinyl group which can be substituted, in the piperazine ring, by a phenyl lower alkyl group which can have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a lower alkyl pyridyl group, (17) a lower alkyl group substituted with a amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imino group idazolyl lower alkyl, (21) a lower alkyl group substituted with 1,2,3,4-tetrahydroisoquinolylcarbonyl, (22) a piperidinylcarbonyl group which may have a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group , and a furilo alkyl group lower as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group which may be substituted, on the piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a lower alkyl furyl group, (25) a lower alkyl carbonyl group substituted by a group [Formula 49] , (26) a lower alkyl carbonyl group substituted by a group [Formula 50] (27) a group -C0-B2o-N (R36) R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a lower alkyl morpholino group, (28a) a lower alkenyl phenyl group, (29a) an anilinocarbonyl alkyl group lower one which may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group which may have, as a substituent on the ring of piperazine, a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino lower alkyl group which may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group which may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group which may have a lower alkyl group as a substituent, (36a) an oxalyl group substituted with piperazinyl which may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent (s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent (s) on the piperazine ring, or (37a) a lower alkyl group s substituted with cyano, R34 represents an oxo group or a phenyl group, d represents an integer from 0 to 3, B2o represents a lower alkylene group, R36 and R37, together with the nitrogen atom to which they are attached, can bind to each other , directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups which may have a lower alkylenedioxy group on the phenyl ring, may be present as a substituent (s), R14 and R15, together with the nitrogen atom to which it is attached. they join, they can be joined to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated or unsaturated 5- to 10-membered heterocyclic ring; or a group [Formula 51] wherein, in the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a lower alkyl group substituted with phenyl, having 1 to 2 phenyl groups which may be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, an atom of halogen, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and an alkylenedioxy group lower, and which may have a pyridyl group in the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group which may have, as a substituent (s) in the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the pyrrole ring, (32) a benzoxazolyl lower alkyl group, (33) a lower alkyl benzothiazolyl group, (34) ) a furyl lower alkyl group, (35) a benzoyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group which can have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene group lower alkyl which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a piperazinyl group, (38) a pyridyl group, (39) n lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkyl group that can be substituted, in the ring of thiazolidine, by a group selected from the group consisting of an oxo group and a group [Formula 52] R --N-N = Rb (wherein Ra and Rb each represents a lower alkyl group), (41) a lower alkyl group which may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a group lower alkanoyl which may have a halogen atom as a substituent, (43) a phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl group lower alkyl which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group which may be substituted on the phenyl ring by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a lower alkoxy phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (49) a group - (B? 2CO) t-N (R20) R21, (50) a group - (CO) or -B? 3- N (R22) R23, (51) a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which can be substituted, on the 1, 2, 3, 4-tetrahydronaphthalene ring, by 1 to 5 lower alkyl groups as a substituent (s), (52) a cycloalkyl group which can having a hydroxyl group as a substituent, (53) a piperidinyl group which may be substituted, on the piperidine ring, by 1 to 3 lower alkyl groups as a substituent (s), (54) a lower alkyl quinolyl group, (55) ) a 1, 2, 3, 4-tetrazolyl group lower alkyl which may have a group selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group which may have a phenyl group as a substituent in the thiazole ring, (57) a benzoyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent (s) on the phenyl ring, (58) a piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group which may have 1 to 3 phenyl groups as a substituent (s) on the imidazole ring, (60) a benzimidazolyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the benzimidazole ring, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may be of having an oxo group as a substituent on the tetrahydroquinoline ring, (63) a 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, ( 64) a cycloalkyl lower alkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) a pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring, (68) a group hydroxyl, (69) a carboxy group, (70) a group lower alkoxy lower alkyl, (71) a lower alkoxy lower alkoxy group, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a carboxy lower alkoxy group, (75) a phenoxy lower alkanoyl group, (76) a 1, 2, 3, 4-tetrahydroquinolylcarbonyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, (77) a phenylsulfonyl group, (78) a lower alkanoyl imidazolyl group, (79) a group imidazolyl lower alkyl, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkoxycarbonyl lower alkyl group, (83) a carboxy lower alkyl group, (84) a group - (O-B15) s- CO-N (R26) R27, (85) a group -N (R28) -CO-B? 6-N (R29) R30, (86) a group -N (R31) -B? 7-CO-N ( R32) R33, (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent in the tetrahydroquin ring lina, B12 represents a lower alkylene group, t represents 0 or 1, R20 and R21 may be identical or different and each represents a hydrogen atom; an amino group which may have a lower alkoxycarbonyl group as a substituent; a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 groups phenyl which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which can be having a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group which may have 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent on the pyrrolidine ring; a lower alkyl group substituted with amino which may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as a substituent (s) on the 1,2,3,4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a lower alkyl pyridyl group; a quinolyl lower alkyl group; a 1, 2, 3, 4-tetrazolyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group as a substituent (s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group; a phenoxy lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent (s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group which may have a halogen atom as a substituent; a lower alkanoyl imidazolyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a lower alkyl carboxy group, or a cycloalkyl group; and R20 and R21, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 7. members (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group which may have 1 to 3 groups selected from the group consisting of one atom of halogen and a lower alkyl group which may have a halogen atom as a substituent (s) on the phenyl ring, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), or represent 0 or 1, B13 represents a lower alkylene group, R22 and R23 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a Phenyl group, or R22 and R23, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring. 5 to 7 members (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may be have a lower alkylenedioxy group as a substituent on the phenyl ring), B15 represents a lower alkylene group, s represents 0 or 1, R26 and R27 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or a group imidazolyl lower alkyl, and R26 and R27, together with the nitrogen atom to which they are attached, can be attached to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring from 5 to 7 members, (wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups which may have a lower alkylenedioxy group as a substituent, may be present on the phenyl ring, as a substituent (s)), R28 represents a hydrogen atom or a lower alkyl group, Biß represents a lower alkylene group, R29 and R30, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, atom of oxygen, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of one group lower alkyl, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, R 31 represents a hydrogen atom or a lower alkyl group, B 17 represents a lower alkylene group, R32 and R33, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic group of 5-7 members , (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), as long as the aforementioned compound or a salt thereof satisfies the following requirements (i) to (v): (i) when Xi represents a group -CH =, then R3 represents a hydrogen; (ii) when Xi represents a group -CH =, 1 represents 1, T represents -CO-, and R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents the group (24); (iii) when Xi represents a group -CH =, 1 represents 1, and T represents -N (R17) -B3-CO-, R14 and R15, together with the nitrogen atom to which they are attached, can bind to each other , directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated or unsaturated 5 to 10 membered heterocyclic ring, in where, in the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent (s); (iv) when Xx represents a nitrogen atom, and 1 represents 0, or when Xi represents a nitrogen atom, 1 represents 1, and T represents -CO- or -S02, R15 is not a group (5), (7) ), (19), or (20); and (v) when R6 represents a cycloalkyl group which may have on the cycloalkyl ring, a substituent selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have one atom of halogen as a substituent, R4 represents a group - (T)! -N (R14) R15 (wherein T and 1 are the same as those described above, and R14 and R15, together with the nitrogen atom to which they are attached, they can be linked to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 10 members, or R14 and R15 form a group [Formula 53] 54. Use of a compound represented by the general formula (1) below or a salt thereof to make an antitumor agent: [Formula 54] wherein Xi represents a nitrogen atom or a group -CH =, R1 represents a group -Z-R6, Z represents a group -N (R8) -B-, a group -B-N (R8) -, a group -Bo ~ 0-, a group [Formula 55] -NHCO- SZ. a group -CO-, a group -CH (OH) -, a group -N (R9a) -CO-N- (R9b) -, a group -N = CH-, a group -N (R10a) -S02- (B22a) e-, a lower alkenylene group, a -NHCO-Bi- group, a -NHCO-B2- (W) u- group, a -BO-0-B? 9a- group, a group [Formula 56] , a group [Formula 57] , a -S02-N (R10b) -, a -S- group, a lower alkynylene group, a lower alkylene group, a -N (R8d) - or a -CO-NH-Bl8a- group. R8 represents a hydrogen atom, a lower alkyl group which may have a lower alkoxy group as a substituent, a lower alkanoyl group, a lower alkylsulfonyl group or a lower alkyl phenyl group, B represents a -CO- group or a lower alkylene group , B0 represents a lower alkylene group, Bi represents a lower alkenylene group which may have a phenyl group as a substituent, B2 represents a lower alkylene group which may be substituted by a group selected from the group consisting of a lower alkoxy group and a group phenyl, R9a represents a hydrogen atom or a lower alkyl group, R9b represents an atom of hydrogen or a lower alkyl group, R10a represents a hydrogen atom or a lower alkyl group, B22a represents a lower alkylene group or a lower alkenylene group, e represents 0 or 1, B? 8a represents a lower alkylene group, Biga represents a lower alkylene group, B2oa represents a lower alkylene group, B2? A represents a lower alkylene group, k represents 2 or 3, c represents 0 or 1, d 'represents 0 or 1, R10b represents a hydrogen atom or a lower alkyl group, R8d represents a hydrogen atom or a lower alkyl group, represents an oxygen atom, a group -NH-, or a sulfur atom, u represents 0 or 1, R6 represents a 5- to 15-membered monocyclic, dicyclic or tricyclic saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or hydrogen atoms; sulfur (which may have 1 to 3 substituents, which are selected from the group consisting of an oxo group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkyl group which can have a halogen atom as a substituent; a halogen atom; a lower alkylsulfonyl group; a phenyl group which may be substituted by a lower alkyl group which may have a halogen atom on the phenyl ring; a lower alkylthio group, a pyrrolyl group, a benzoyl group; a lower alkanoyl group; lower alkoxycarbonyl group; and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the heterocyclic ring), an adamantyl group, a naphthyl group (which may have 1 to 3 groups selected of the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, on the naphthalene ring), a alkyl group which can have a lower alkoxy group as a substituent, a cycloalkyl group which can be substituted by a group selected from the group consisting of a lower alkyl group substituted with amino which can have a lower alkyl group and a lower alkyl group which can be have a halogen atom as a substituent, in the cycloalkyl ring, a lower alkenyl group which may have a halogen atom as a substitute of the group consisting of a lower alkyl group which can have 1 to 3 groups selected from the group consisting of a lower alkyl group which can be selected from the group consisting of a lower alkanoyl group, a benzoyl group having a halogen atom and halogen atom, as a substituent, on the phenyl ring), a lower alkyl group substituted with halogen atom, cycloalkyl lower alkyl group or a group [Formula 58] R7 represents a hydrogen atom, a phenyl group, a carboxy group, a hydroxyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a phenoxy group, a lower alkoxy group which may have a halogen atom as a substituent, a lower alkylenedioxy group, an amino group which may have, as a substituent, a group selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group, and a cycloalkyl group , a cyano group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkylsulfonyl group, an aminosulfonyl group, a lower alkoxycarbonyl group, a lower alkanoyloxy group, a lower alkoxycarbonyl lower alkyl group or a heterocyclic group of 5 or 6 saturated or unsaturated members having 1 to 4 nitrogen atoms, oxygen atoms, or sulfur atoms (which may have a group or xo in the ring heterocyclic), m represents an integer from 1 to 5 (when m represents 2 to 5, two to five R7s can be identical or different) and R2 represents a hydrogen atom, a halogen atom, or a lower alkyl group, Y represents a group -O-, a group -N (R5) -, a group -CO-, a group -CH (OH) -, a lower alkylene group, a -S (0) n- group, or a -C group (= N-OH) -, R5 represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a benzoyl group, a phenyl lower alkyl group, or a cycloalkyl group, n represents 0, 1, or 2, A represents a group [Formula 59] or a group [Formula 60] p represents 1 or 2, R3 represents a hydrogen atom, a lower alkoxy group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxycarbonyl group, a carboxy group, a -CONR- ^ R12 group, or a cyano group, wherein R11 and R12 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, or a phenyl group, and R11 and R12, together with the nitrogen atom to which they bind, they can bind to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, R4 represents an imidazolyl lower alkyl group, a group 1 , 2,4-triazolyl lower alkyl, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group which may have an oxo group as a substitute in the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1, 2 ring, 4-oxadiazole, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a group [Formula 61] , a group [Formula 62] or a group - (T) 1-N (R 114 V,> 15 R> 13 represents a hydrogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkanoyl group which may have an halogen atom as a substituent, a lower alkoxycarbonyl group, a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl imidazolyl group, a lower alkoxycarbonyl lower alkyl group, a lower alkyl carboxyl group , a benzoyl group, a lower alkanoyl group substituted with morpholino, a piperazinyl carbonyl lower alkyl group which may be substituted, on the piperazine ring, by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring , a piperazinyl lower alkyl group which can be substituted, in the piperazine ring, for a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, a lower alkyl group substituted with raorfolinocarbonyl, or a lower alkanoyl imidazolyl group, R13a represents a hydrogen atom or a hydroxyl group , T represents a lower alkylene group, a group - N (R17) -B3-CO-, a group -B19-N (R18) -CO-, a group -B4-CO-, a group -Q-B5-CO -, a group -B6-N (R19) -B7-CO-, a group -CO-B8-, a group -CH (OH) -B9-, a group -CO-B? 0-CO-, a group -CH (OH) -B11-CO-, a group -CO-, a group -S02-, or a group -B23a_CO-CO-, wherein R17 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a lower alkanoyl group which may have a halogen atom as a substituent, a lower alkenyl group, a lower alkanoyl group substituted with amino which may have a lower alkyl group as a substituent, or a group lower alkylsulfonyl, B3 represents a lower alkylene group, B19 represents a lower alkylene group, R18 represents a hydrogen atom or a lower alkyl group, B4 represents a lower alkenylene group or a lower alkylene group which may have a hydroxyl group as a substituent, Q represents an oxygen atom or a group -S (0) n- (wherein n is equal to that described above), B5 represents a lower alkylene group, B6 represents a lower alkylene group, R19 represents a lower alkyl group, hydrogen or a lower alkanoyl group, B7 represents a lower alkylene group, B8 represents a lower alkylene group, B9 represents a lower alkylene group, Bo represents a lower alkylene group, Bu represents a lower alkylene group, B23a represents a lower alkylene group, represents 0 or 1, R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents (2) an alkyl group substituted with a hydroxyl group, (3) a cycloalkyl group which may have a group selected from the group consisting of a hydroxyl group and a lower alkyl group as a substituent, (4) a phenoxy lower alkyl group, (5) a phenyl group which can be substituted, in the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have an halogen as a substituent; a halogen atom; a lower alkoxy amino group which may have a lower alkyl group as a substituent; a lower alkyl group substituted with a hydroxyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; a lower alkanoylamino group; a cyano group; and a phenoxy group, (6) a phenoxy group, (7) a phenyl lower alkyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group, (8) a phenyl lower alkyl group having a lower alkylenedioxy group as a substituent on the phenyl ring, (10) a lower alkyl group substituted with lower alkoxycarbonyl , (11) a lower alkyl group substituted with carboxy, (12) an amino group which may have an lower alkanoyl group as a substituent, (13) a 1, 2, 3, 4-tetrahydroquinolyl group which may have 1 to 3 groups selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group as a substituent (s) on the tetrahydroquinoline ring, (14) a cycloalkyl lower alkyl group, (15) a piperazinyl lower alkyl group which may be substituted, on the piperazine ring , by a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (16) a pyridyl lower alkyl group, (17) a lower alkyl group substituted with an amino group which may have a group selected from the group consisting of a group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, (18) a lower alkoxy lower alkyl group, (19) an imidazolyl group, (20) an imidazolyl lower alkyl group, (21) a lower alkyl group substituted with 1,2,3,4-tetrahydroisoquinolylcarbonyl, (22) a piperidinylcarbonyl group which may have a group selected from the group consisting of a lower alkoxycarbonyl group, an alkyl phenyl group lower, and a furyl lower alkyl group as a substituent on the piperidine ring, (23) a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, (24) a piperidinyl group which may be substituted , at 1 piperidine ring, by a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group, and a lower alkyl furyl group, (25) a lower alkyl carbonyl group substituted by a group [Formula 63] í -N , (26) a lower alkyl carbonyl group substituted by a group [Formula 64] (27) a group -CO-B20-N (R36) R37, (26a) a pyrrolidinyl lower alkyl group, (27a) a lower alkyl morpholino group, (28a) a lower alkenyl phenyl group, (29a) an anilinocarbonyl alkyl group lower, which may have a lower alkyl group as a substituent on the phenyl ring, (30a) an indolyl group, (31a) a piperazinyl lower alkyl group which may have, as a substituent on the piperazine ring, a group selected from the group it consists of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring, (32a) an amidino group lower alkyl which may have a lower alkyl group as a substituent, (33a) a fluorenyl group, (34a) a carbazolyl group which may have a lower alkyl group as a substituent on the carbazole ring, (35a) an amidino group which may having a lower alkyl group as a substituent, (36a) an oxalyl group substituted with piperazinyl which may have 1 to 3 groups selected from the group consisting of a phenyl lower alkyl group (which may have 1 to 3 groups selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group as a substituent (s) on the phenyl ring) and a pyridyl lower alkyl group as a substituent (s) on the piperazine ring, or (37a) a lower alkyl group substituted with cyano, R34 represents an oxo group or a phenyl group, d represents an integer from 0 to 3, B2o represents a lower alkylene group, R3d and R37, together with the nitrogen atom to which they are attached, can be attached to each other. or, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups may have a lower alkylenedioxy group on the phenyl ring, can be present as a substituent (s), 1 R14 and R15, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered heterocyclic ring saturated or unsaturated; or a group [Formula 65] wherein, in the heterocyclic ring, 1 to 3 substituents may be present which are selected from the group consisting of (28) a lower alkyl group substituted with phenyl, having 1 to 2 phenyl groups which may be substituted by 1 to 3 groups on the phenyl ring, selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, an atom halogen, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy group, and which may have a pyridyl group in the lower alkyl group, (29) a carbamoyl group, (30) a pyridyl lower alkyl group which may have, as a substituent (s) in the pyridine ring, 1 to 3 groups selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent, (31) a pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the ring of pyrrole, (32) a benzoxazolyl lower alkyl group, (33) a benzothiazolyl lower alkyl group, (34) a furyl lower alkyl group, (35) a benzoyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, an amino group which may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group, (36) a pyrimidinyl group, (37) a piperazinyl group, ( 38) a pyridyl group, (39) a lower alkoxycarbonyl group, (40) a thiazolidinyl lower alkyl group that can be substituted, on the thiazolidine ring, by a group selected from the group consisting of in an oxo group and a group [Formula 66] Ra: N-N = (Rb (wherein Ra and R each represents a lower alkyl group), (41) a lower alkyl group which may have a group selected from the group consisting of a hydroxyl group and a halogen atom as a substituent, (42) a group lower alkanoyl which may have a halogen atom as a substituent, (43) a phenyl group which may be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl group lower alkyl which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group, (44) a phenyl group which may have an alkylenedioxy group lower as a substituent on the phenyl ring, (45) a naphthyl lower alkyl group, (46) a phenoxy group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (47) a phenoxy lower alkyl group, (48) a phenyl lower alkoxy group which may be substituted on the phenyl ring by 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent, (49) a group - (B? 2CO) tN (R20) R21, (50) a group - (CO) or B? 3-N (R22) R23, (51) a lower alkyl group substituted with 1 , 2, 3, 4-tetrahydronaphthyl that can be substituted, in the 1, 2, 3, 4-tetrahydro ring naphthalene, from 1 to 5 lower alkyl groups as a substituent (s), (52) a cycloalkyl group which may have a hydroxyl group as a substituent, (53) a piperidinyl group which may be substituted, in the piperidine ring, by 1 to 3 lower alkyl groups as a substituent (s), (54) a lower alkyl quinolyl group, (55) a 1,2,3,4-tetrazolyl lower alkyl group which may have a group selected from the group consisting of lower alkyl group and a group phenyl lower alkyl as a substituent on the tetrazole ring, (56) a thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring, (57) a lower alkyl benzoyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group and a halogen atom as a substituent (s) on the phenyl ring, (58) a lower alkyl piperidinyl group which may have a lower alkyl group as a substituent on the piperidine ring, (59) an imidazolyl group which may have 1 to 3 phenyl groups as a substituent (s) on the imidazole ring, (60) a benzimidazolyl group which may have 1 to 3 lower alkyl groups as a substituent (s) on the ring of benzimidazole, (61) a pyridyl lower alkoxy group, (62) a 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, (63) a group 1, 3, 4-oxadiazolyl at lower alkyl which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring, (64) a lower alkyl cycloalkyl group, (65) a tetrahydropyranyl group, (66) a thienyl lower alkyl group, (67) ) a pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring, (68) a hydroxyl group, (69) a carboxy group, (70) a lower alkoxy lower alkyl group, (71) a lower alkoxy group lower alkoxy, (72) a benzoyloxy group, (73) a lower alkoxycarbonyl lower alkoxy group, (74) a lower alkoxy carboxy group, (75) a lower alkanoyl phenoxy group, (76) a 1,2,3,4-tetrahydroquinolylcarbonyl group which may have an oxo group as a substituent on the ring of tetrahydroquinoline, (77) a phenylsulfonyl group, (78) a lower alkanoyl imidazolyl group, (79) an imidazolyl lower alkyl group, (80) a pyridylcarbonyl group, (81) an imidazolylcarbonyl group, (82) a lower alkyl alkoxycarbonyl group lower, (83) a carboxy lower alkyl group, (84) a group - (O-B15) s-CO-N (R26) R27, (85) a group -N (R28) -CO-B? 6-N (R29) R30, (86) a group -N (R31) -B1 -CO-N (R32) R33, (87) a benzoxazolyl group, (88a) a benzothienyl group, (89a) an oxo group, and (90a) ) a 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring, B12 represents a lower alkylene group, t represents 0 or 1, R20 and R21 may be identical or different and each represents a hydrogen atom; an amino group which may have a lower alkoxycarbonyl group as a substituent; a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) on the phenyl ring; a lower alkyl group; a lower alkyl group having 1 to 2 phenyl groups which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of one group lower alkoxycarbonyl, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group; a phenyl group which can be substituted, on the phenyl ring, by 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent; a lower alkoxycarbonyl group; a cycloalkyl lower alkyl group; a pyrrolidinyl lower alkyl group which may have 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent on the pyrrolidine ring; a lower alkyl group substituted with amino which may have a group selected from the group consisting of a phenyl group and a lower alkyl group as a substituent; a lower alkyl group substituted with 1, 2, 3, 4-tetrahydronaphthyl which may have 1 to 5 lower alkyl groups as a substituent (s) on the 1, 2, 3, 4-tetrahydronaphthalene ring; a naphthyl lower alkyl group; a lower alkyl pyridyl group; a quinolyl lower alkyl group; a 1,2,3,4-tetrazolyl lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a lower alkyl phenyl group as a substituent (s) on the tetrazole ring; a 1,2,4-triazolyl lower alkyl group; a tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent in the lower alkyl group; a phenoxy lower alkyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group and a nitro group as a substituent (s) on the phenyl ring; a phenyl lower alkanoyl group; a lower alkanoyl group which may have a halogen atom as a substituent; a lower alkanoyl imidazolyl group; a lower alkoxycarbonyl lower alkyl group; a pyridyl group; or a lower alkyl carboxy group, or a cycloalkyl group; and R20 and R21, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5-a. 7 members (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group which may have 1 to 3 groups selected from the group consisting of halogen atom and a lower alkyl group which may have a halogen atom as a substituent (s) on the phenyl ring, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), or represents O or 1, B13 represents a lower alkylene group, R22 and R23 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a benzoyl group which may have 1 to 3 lower alkoxy groups as a substituent (s) in the phenyl ring, a phenoxy lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring, a phenyl lower alkyl group, or a phenyl group, or R22 and R23, together with the nitrogen atom to which they join, they can be joined to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic ring (where, in the heterocyclic ring, they can 1 to 3 substituents are present, which are selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), B15 represents a lower alkylene group, s represents 0 or 1, R26 and R27 may be identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, or a lower alkyl imidazolyl group, and R26 and R27, together with the nitrogen atom to which they are attached, can bind to each other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic ring, (wherein, in the heterocyclic ring, 1 to 3 phenyl lower alkyl groups may have a lower alkylenedioxy group as a substituent, may be present on the phenyl ring, as a substituent (s)), R28 represents a hydrogen atom or a lower alkyl group, Bi6 represents a lower alkylene group, R29 and R30, together with the atom of nitrogen to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 7-membered saturated heterocyclic group, wherein, in the heterocyclic ring , 1 to 3 substituents may be present, which are selected from the group consisting of a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group or a substituent on the phenyl ring, R31 represents a hydrogen atom or a lower alkyl group, B17 represents a lower alkylene group, R32 and R33, together with the nitrogen atom to which they are attached, can be attached to each other, directly or through a nitrogen atom, oxygen atom, or sulfur atom to form a saturated 5- to 7-membered heterocyclic group, (wherein, in the heterocyclic ring, 1 to 3 substituents may be present, which are selected from the group consisting of in a lower alkyl group, a phenyl group, and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring), provided that the aforementioned compound or a salt thereof satisfies the following requirements (i) ) a (v): (i) when Xi represents a group -CH =, then R 'represents a hydrogen atom; (ii) when Xi represents a group -CH =, 1 represents 1, T represents -CO-, and R14 represents a hydrogen atom or an alkyl group which may have a hydroxyl group as a substituent, R15 represents the group (24); (iii) when Xi represents a group -CH =, 1 represents 1, and T represents -N (R17) -B3-CO-, R14 and R15, together with the nitrogen atom to which they are attached, can bind to each other , directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated or unsaturated 5- to 10-membered heterocyclic ring, wherein, in the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent (s); (iv) when Xi represents a nitrogen atom, and 1 represents 0, or when Xi represents a nitrogen atom, 1 represents 1, and T represents -CO- or -S02, R15 is not a group (5), (7) ), (19), or (20); and (v) when R6 represents a cycloalkyl group which may have on the cycloalkyl ring, a substituent selected from the group consisting of a lower alkyl group substituted with amino which may have a lower alkyl group and a lower alkyl group which may have one atom of halogen as a substituent, R4 represents a group - (T) iN (R14) R15 (wherein T and 1 are the same as those described above, and R14 and R15, together with the nitrogen atom to which they are attached, can bind one to the other, directly or by means of a nitrogen atom, oxygen atom, or sulfur atom to form a saturated heterocyclic ring of 5 to 10 members, or R14 and R15 form a group [Formula 67] 55. The use according to claim 54, wherein a target of the antitumor agent is a malignant turator. 56. The use according to claim 55, wherein the malignant tumor is a solid tumor. 57. The use according to claim 55, in where the malignant tumor is a hematologic cancer. 58. The use according to claim 55, wherein the malignant tumor is lymphoma, leukemia or myeloma. 59. The antitumor agent according to any of claims 44 to 47, characterized in that R14 and R15, together with the nitrogen atom to which they are attached, are bound to each other, directly or through a nitrogen atom to form a saturated 6-membered heterocyclic group which is substituted, on the heterocyclic ring, by a lower alkyl group substituted with phenyl which can be substituted, on the phenyl ring, by 1 or 2 group (s), as its tit uyent e (s ), selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and an alkyl group Uilendioxi inferior. 60. The antitumor agent according to claim 59, characterized in that the saturated heterocyclic group is a piperazinyl group which is replaced by a lower alkyl group substituted with phenyl which is substituted by a lower alkylenedioxy group on the phenyl ring. 61. The antitumor agent according to claim 59 or 60, characterized in that Xi is a nitrogen atom and Y is an oxygen atom.