TW200918053A - Heteroaryl benzene compound - Google Patents

Abstract

Heteroarylbenzene compounds represented by the general formula (1): (1) [wherein A is N or CH; R1 is hydrogen or C1-8 alkyl; R2a and R2b may be the same or different and are each a group selected from the group consisting of hydrogen, halogeno, and C1-6 alkyl: Q is substituted or unsubstituted phenyl, benzyl, naphthyl, tetrahydronaphthyl, C3-10 cycloalkyl, or the like; m is 0 or 1; n is 0 or 1; X is -O- or -NR3-; and Y is substituted or unsubstituted C1-8 alkylene or the like]; tautomers, stereoisomers or pharmaceutically acceptable salts of the compounds; or solvates of the same are useful as drugs for the prevention or treatment of diseases or symptoms which can be ameliorated by the inhibition of DGAT1, for example, obesity, hyperlipemia, hypertriglyceridemia, lipometabolic disorder, diabetes, arteriosclerosis; or obesity-caused, hyperlipemia, hypertriglyceridemia, lipometabolic disorder, diabetes, arteriosclerosis or hypertension.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel heteroarylbenzene compound having a hindrance effect of DGAT1 (dimercaptoglycerol thiol transferase 1) and a medicament containing the same as an active ingredient. [Prior Art] DGAT 1 is mainly found in the small intestine or adipose tissue. The enzyme which synthesizes triglyceride (neutral fat) from dimercaptoglycerin is absorbed in the small intestine to absorb glycerol and fatty acids in intestinal epithelial cells. It is converted into triglyceride by DG AT 1 and, by the action of MTP (microsomal triglyceride transporter), the constituent lipids of the chylomicrons are combined, released into lymphatic vessels, and then transported to the liver. The glycerol and fatty acid taken up by the fat cells are converted into triglycerides by DGAT1 and stored. If the process is abnormally hypertrophy, the fat cells are hypertrophied, and a large amount of malignant physiologically active substances such as TNFα (adipocyte factor A di ρ 〇cyt 〇ki :nes ) are secreted, and the secreted adipocytokines cause osteoblasts and liver. The cells are insulin resistant, have reduced sugar uptake and fat synthesis. In 1998, DGAT1 reported the cloning of each mouse and homologous in different groups (refer to Non-Patent Documents 1, 2), and in 2000, through the analysis of DGAT1 gene knockout mice, metaphor as an important target molecule for obesity treatment. The importance of DG ATI (refer to Non-Patent Document 3), this DGAT1 gene knockout mouse 'when it is a normal diet, there is no difference in body weight from normal mice, and the amount of neutral fat is only slightly reduced, but the amount of body fat is intentional-6- 200918053 Reduced land, but when it is a high-fat diet, weight gain is also strongly suppressed, and the amount of fat in various parts of the body is also significantly reduced, and the amount of neutral fat is also reduced. In the above, the substance which inhibits DGAT1 (hereinafter referred to as DGAT1 inhibitor) is desired to cause obesity, hypertriglyceridemia, and sugar tolerance by inhibiting the production of triglyceride in the small intestine and/or adipose tissue. Diseases such as abnormalities are effective therapeutic drugs. In the prior art, as a DGAT 1 hindrance substance, although certain biaryl compounds, biphenyl carbonyl compounds, benzidine acid compounds, pyrimidoxazine compounds, urea compounds, guanamine compounds have been reported, the present invention has not been disclosed. Compound (refer to Patent Documents 1, 2, 3, 4, 5, and 6). Further, reports of similar compounds have been constructed, but the compounds of the present invention have not been specifically disclosed, and are different from the use of the compounds of the present invention (see Non-Patent Document 4, Patent Document 7, and Patent Document 8). [Non-Patent Document 1] Cases S et al. Proceeding of the National Academy of Sciences of the United States of America, 95, 13018-13023, 1998 [Non-Patent Document 2] Oelkers P et al. The Journal of biological chemistry, 273 , 26765-2677 1,1998 [Non-Patent Document 3] Smith SJ et al· Nature Genetics, 25, 87-90, 2000 [Non-Patent Document 4] Zhili Xin et al. Journal of Medicinal

Chemistry 49, 15? 4459-4469, 2006 [Patent Document 1] W007/1 37 1 07 200918053 [Patent Document 2] W004/100881 [Patent Document 3] W007/0 1 653 8 [Patent Document 4] WO04/047755 [ Patent Document 5] W006/01 9020 [Patent Document 6] WO06/082952 [Patent Document 7] WO07/03 8669 [Patent Document 8] WO 00/05 5 1 3 9 [Summary of the Invention] [Problems to be Solved by the Invention] An object of the present invention is to provide a compound which is excellent as a DGAT1 inhibitory action. [Means for Solving the Problem] The inventors of the present invention have found a heteroarylbenzene compound represented by the general formula (1) or a pharmaceutically acceptable compound thereof in order to find a result of careful investigation of a compound having a DGAT1 inhibitory action. Salt can achieve this purpose and the present invention is completed. That is, the present invention (I) provides a heteroarylbenzene compound represented by the formula (1), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof, or a solvate thereof , -8- 200918053

(In the formula (1), A represents N or CH; R1 represents a hydrogen atom or a Ci-8 fluorenyl group; and the ruthenium 23 and R2b represent the same or different groups selected by a hydrogen atom or a group of halogen atoms; The Ch6 alkyl group Q represents a phenyl group (the phenyl group is unsubstituted, C!-6 alkoxy group (the C, -6 alkoxy group is not substituted with a fluorine atom), a halogen atom, a trifluoromethyl group or is selected from C , - 8 alkyl, 'or 1 to 5, cyano, hydroxy, ethyl hydrazine

An oxy group, a methylenedioxy group (which is substituted with 1 or 2 fluorines (atoms substituted), a phenyl group, a cl6 which is burned for the back 6 alkylthio group, and Cw The same or different mussels formed by the alkyl group thiol group - the king: s base is substituted, the base (the base is not substituted, or the sleeve is replaced or 1 to 2 Cl.3 yards) The base of the two fluorine atoms is 佧); the substituent) n-, tetraaminocaline, or % ring-burning m represents 0 or 1; η represents 0 or 1; X represents not -0-, or _NR3_ Wherein r3 represents a hydrogen atom' or (the Cl-8 fluorenyl group may also bond with a carbon atom of γ to form a 5-membered heterocyclic ring)) C. -8 to 7 -9- 200918053 Y Cl·8 is not substituted, or is substituted by the same or different 1 to 2 groups of C!·6 alkyl and hydroxyCl.6 alkyl groups, the C!_s alkylene One of the carbon atoms of the group may be substituted by an oxygen atom. 'One of the carbon atoms of the C!-8 alkyl group may be a cycloalkane containing 3 to 6 members formed by the carbon atom itself, or 3 A member of the heterocyclic ring of 6 members)). (Π) Another embodiment of the present invention provides a heteroarylbenzene compound represented by the formula (2), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof , [Chemical 2

(In the formula (2), A represents N or CH; R1 represents a hydrogen atom or a Cu alkyl group; R2 represents a hydrogen atom, a halogen atom, or Q represents a phenyl group (the phenyl group is unsubstituted, or c, or c) 1 · 8 alkyl; ί, a halogen atom, or (the phenyl group is unsubstituted, the oxy group (the C, -6 alkoxy group is unsubstituted, or is cc^6 fluorenyl) amine group The same or different j to 3 atomic groups of the selected group of a single atom, a trifluoromethyl group, a trifluoromethoxy group, or a gas radical thio group, a Ci.8 alkyl group, (^. 6 alkane C 1 -6-oxime, and a substituent of two (substituted by a group), a halogen-block, a hydroxyl group, and a group of three bases of c. 6-alkane), a base group (the base group is unsubstituted) or Being -2

C ^ 3 alkyl substituted 200918053 ), or C3-1G cycloalkyl; m represents 0 or 1; η represents 0 or 1; X represents - 0-, or -NR3- (wherein R3 represents a hydrogen atom, or Ci8 yard base (the Ci-8 yard base can be bonded to the carbon atom of Y to form a heterocyclic ring of 5 to 7 members)); Y is not C!·8 extension yard base (the Ci·8 extension yard base is not Substituted, or substituted by the same or different one or two groups selected from the group consisting of C!-6 alkyl and hydroxy C..6 alkyl, which are in the carbon atom of the Ci-8 One of the carbon atoms may be substituted by an oxygen atom, and one of the carbon atoms of the Ci_8 alkyl group may be a member of a cyclohexane having 3 to 6 members formed by the carbon atom itself, or a heterocyclic ring of 3 to 6 members. )). (III) Another aspect of the present invention provides a heteroarylbenzene compound represented by the formula (3), a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof ,

(In the formula (3), A represents N or CH; R1 represents a hydrogen atom or an alkyl group; R2 represents a hydrogen atom, a halogen atom, or a Cl.6 alkyl group; -11 - 200918053 Q represents a benzyl group (the phenyl group is not Substituted, or substituted by the same or different 1 to 3 groups of a group consisting of a Cu alkyl group, a CCl 6 alkoxy halogen atom, and a trifluoromethyl group; γ represents a Ci alkyl group ( The alkylene group is unsubstituted or substituted by the same or different i to 2 groups selected from the group consisting of Cl. 6 alkyl and hydroxy C!-6 alkyl, 胄C 1. One of the carbon atoms of the alkyl group may be substituted by an oxygen atom. One of the carbon atoms of the C8 alkyl group may be a ring of 3 to 6 members formed by the carbon atom itself, or 3 to 6 Member of the heterocyclic ring)). (IV) Another aspect of the present invention provides the heteroarylbenzene compound of (1) represented by formula (4), a tautomer of the compound, a JX isomer, or a pharmaceutically acceptable compound thereof Salt or such solvate, [4]

Q

Human 0, R1 (Q in the formula (4) represents a phenyl group (the phenyl group is unsubstituted, or is a Ci 8 alkyl group, a oxyl group, a halogen atom, a trifluoromethyl group, a trifluoromethoxy group, a cyano group) And the same or different 1 to 3 groups of the group formed by the methyloxy group (the methylenedioxy group is unsubstituted or substituted by two fluorine atoms)) , Rl, R2b, and γ are defined as (!). (V) another % of the present invention provides a heteroarylbenzene compound of the formula (5), a tautomer of the compound, a stereoisomer of -12-200918053, or a pharmaceutically acceptable salt or a solvate thereof

(In the formula (5), Q represents a phenyl group (the phenyl group is unsubstituted or is represented by a C, -8 alkyl group, a Ci-6 alkoxy group, a halogen atom, a di-methyl group, and a trifluoromethoxy group). Substituted by the same or different groups of 1 to 3): 111 represents a hydrogen atom 'or C'. 3 alkyl; R2b represents a hydrogen atom ''R2a, and A is as defined in (IV)). (VI) The other aspect of the invention provides the heteroarylbenzene compound described in (V), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, A is N, R1 is a hydrogen atom, the caliper 23 is a hydrogen atom or a methyl group, and the caliper 21) is a hydrogen atom. (VII) Another aspect of the present invention provides the heteroarylbenzene compound according to (V), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof; A is CH, R1 is a hydrogen atom, and R23 and R2b are a hydrogen atom. (VIII) The other aspect of the invention provides the heteroarylbenzene compound of the formula (6), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof Or such solvates-13- 200918053

(In the formula (6), R1 represents a hydrogen atom or a Ci-3 group; P represents an integer of 1 to 4', R2a, R2b and q are as defined in (iv). (IX) The other aspect of the invention provides the heteroarylbenzene compound of (VIII), a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, A is N, R1 is a hydrogen atom, R2a, and 1121> are a hydrogen atom 'Q represents a phenyl group (the phenyl group is unsubstituted, or is Ci-8, a Ci_6, a oxy atom, a trifluoromethyl) The group consisting of the same or different 1 to 3 groups of the group formed by the trifluoromethoxy group; p is an integer of 1 to 3.

(X) another aspect of the invention provides a heteroarylene compound, a tautomer, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, as described in (v) Α is CH. R1 is a hydrogen atom, and R2a and R2b are hydrogen atoms? An integer of 1 to 3. (XI) The other aspect of the invention provides the heteroarylbenzene compound of (VIII), a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, A is N, R] is a hydrogen atom, R2a is a methyl group, a chlorine atom, or a fluorine atom, R2b is a hydrogen atom, a chlorine atom, or a fluorine/atom 'Q represents a phenyl group (the-14-200918053 is unsubstituted) 'Or substituted by the same or different 1 to 3 groups of the group consisting of Cl alkyl, Ci 6 alkoxy, halogen atom, and 'trifluoromethoxy group; P is 1 to 3 Integer. (ΧΠ) another aspect of the present invention provides the heteroarylbenzene compound of the above (VIII), a tautomer, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof. Α is CH'R1 is a hydrogen atom, a methyl group, a chlorine atom, or a fluorine atom 'R2b is a hydrogen atom, a chlorine atom, or a fluorine atom, and Q represents a phenyl group (the phenyl group is unsubstituted or is a Cl_8 alkyl group, The group of the same or different oximes of the Cl.6 alkoxy group, the halogen atom, the trifluoromethyl group, and the trifluoromethoxy group is substituted with three groups; p is an integer of from 1 to 3. (X111) Another aspect of the present invention provides a heteroarylbenzene compound represented by the formula (7), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or Solvents

(In the formula (7), 'Q' represents a phenyl group (the phenyl group is unsubstituted or is a group formed by a Cu alkyl group, a Ci-6 alkoxy group, a halogen atom, a di-methyl group, and a trifluoromethoxy group). Substituted by the same or different 1 to 3 groups): A ' Ri, R2a, R2b -15- 200918053, and γ are as defined in (i). (XIV) Another embodiment of the present invention provides a heteroarylbenzene compound according to (XIII) represented by the formula (8), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof Or such solvates

(In the formula (8), R1 represents a hydrogen atom or a Cl-3 alkyl group; R2a represents a hydrogen atom; and R2b, A and Q are as defined by (?).

(XV) In another aspect of the invention, the heteroarylbenzene compound described in (xiv), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof is provided A is N, R1 is a hydrogen atom, and R2a and R2b are a hydrogen atom. (XVI) The other aspect of the present invention provides the heteroarylbenzene compound described in (XIV), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof A is CH, R1 is a hydrogen atom, and R2a and R2b are a hydrogen atom. (X V11) Another aspect of the present invention provides the heteroarylbenzene compound of (XIII) represented by the formula (9), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable compound thereof Salt or such solvate, -16- 200918053

(In the formula (9), R1 represents a hydrogen atom or a C!-3 yard group; p represents an integer of 7Κ1 to 4; R2a is a hydrogen atom; R2b, Α and Q are as defined by (XIII)) (XVIII) According to another aspect of the present invention, there is provided a heteroarylbenzene compound according to (XVII), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is N R1 is a hydrogen atom, R2a and R2b are a hydrogen atom, and p is an integer of 1 to 3. (XIX) The other aspect of the invention provides the heteroarylbenzene compound according to (XVII), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, A is CH, R1 is a hydrogen atom, R2a and R2b are a hydrogen atom, and p is an integer of 1 to 3. (XX) Another aspect of the present invention provides the heteroarylbenzene compound of (I) represented by the formula (10), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable compound thereof Salt or such solvate-17- 200918053 ι〇Λ, ^〇,

(10) (In the formula (10), Q, A, R1, R2a, R2b, and Y are defined as (I). (XXI) Another aspect of the present invention provides the heteroarylbenzene compound of (XX) represented by the formula (1 1 ), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable compound thereof Salt or such solvate, [1 1]

(11) (In the formula (11), R1 represents a hydrogen atom or a Ci-3 alkyl group; Q represents a phenyl group (the phenyl group is unsubstituted, or is alkyl group, Cb6 alkoxy group, halogen atom, trifluoromethyl) Substituted with the same or different 1 to 3 groups of the group formed by the trifluoromethoxy group; R2a, and R2b represent a hydrogen atom; A is as defined in (XX). (XXII) Another aspect of the present invention provides the heteroarylbenzene compound according to (XXI), a tautomer of the compound, a stereoisomer-18-200918053, or a pharmaceutically acceptable salt thereof or the like Solvate, A is Ν, Ι^ is a hydrogen atom. (XXIII) Another aspect of the present invention provides (a heteroarylbenzene compound, a tautomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein hydrazine is CH and R1 is a hydrogen atom. (XXIV) Another aspect of the present invention provides the heteroarylbenzene compound of the above (XX), the isomer, the stereoisomer, or a pharmaceutically acceptable salt thereof, as described in XXI) , the stereoisomers (12), the interconversion of the hepta compounds or such solvents

(In the formula (12), 'R1 represents a hydrogen atom or an integer of a C.3 alkyl group, and Q, A, R2a, and r2d are as defined in (XX) (XXV), and other forms of the present invention provide a heteroaryl group. a benzene compound, a tautomer of the compound, or a pharmaceutically acceptable salt thereof or such a solvate A is N, R1 is a hydrogen atom, and R2a, and R2b are a hydrogen phenyl group (the phenyl group is unsubstituted, or Substituted by 1 to 3 groups of a group of an alkyl group, a C-containing atom, a trifluoromethyl group, and a trifluoromethoxy group), and a tetrahydronaphthyl group; p -19 - . ~4 I). :XXIV) Recorded, stereoisomerary>Atom, Q represents an integer of -6 oxime, halogen or the same as 1-3. 200918053 (XXVI) Other aspects of the invention are provided (xx 1 v ) The heteroarylbenzene compound, the tautomer, the stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is CH, R1 is a hydrogen atom, and R2a and R2b are A hydrogen atom, P is an integer of 1 to 3. (XXVII) The other aspect of the invention provides the heteroarylbenzene compound of (XXIV), a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, A is N, I^ is a hydrogen atom, R2a is a methyl group, a chlorine atom, or a fluorine atom 'R2b is a hydrogen atom, a chlorine atom, or a fluorine atom, and Q represents a phenyl group (the phenyl group is unsubstituted or <^-8 alkyl, c^6 alkoxy, halogen atom, difluoromethyl, and trifluoromethoxy group of the same or different groups of 1 to 3 are substituted; P is An integer from 1 to 3. (XXVIII) Another aspect of the present invention provides the heteroarylbenzene compound of (XXIV), a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, A is CH' R1 is a hydrogen atom, a methyl group, a chlorine atom, or a fluorine atom 'R is a hydrogen atom, a chlorine atom, or a fluorine atom, and Q represents a phenyl group (this group is unsubstituted or c18 alkyl group, The group consisting of the same or different 1 to 3 groups of the c16 alkoxy group, the halogen atom, the dioxylmethyl group, and the trifluoromethoxy group; P is an integer of 1 to 3. (XXIX) Another aspect of the present invention provides a heterocyclic benzene compound described below, a tautomer of the compound, a stereoisomer, -20-200918053 or a pharmaceutically acceptable salt thereof or a solvent thereof Compound, 2_((5-[4·(丨[2_methoxy-5-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy) -2 -Methylpropionic acid 3_{[(2,3-dimethoxyphenyl)aminomethylindolyl]amino}phenyl)indole quinone-2-yl]amino} —2,2 -3-methylpropionic acid 3-{[5-(4-{[(2,4-dimethylphenyl)aminomethylindolyl]amino}phenyl)pyridinyl-2-methyl]amino } -2,2-Dimethylpropionic acid 3_ { 〔 5·( 4·丨[(2-chlorophenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]amino} 2,2-Dimethylpropionic acid 3-{[5-(4-{[(2,3-dimethoxyphenyl)aminomethylindolyl]amino}phenyl)pyridin-2 3-[C 5-(4-{[(2-Chlorophenyl)aminomethylmethyl]amino}phenyl)pyridin-2-yl]-[2,2-dimethylpropanoic acid] Oxygen} -2,2-dimethylpropionic acid 3_{ [5_(4_{ 〔(3_ethylphenyl)aminomethylindenyl)amine } phenyl) 卩 Π -2- -2- 基 基 -2- -2- -2- -2- -2- -2- -2- -2- -2- -2- -2- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- 5- Indenyl]amino}phenyl)pyridin-2-yl]oxy}-2,2-dimethylpropionic acid 3-{[5-(4-{[(2,4-dimethylphenyl)amine Methylmercapto]amino}phenyl)pyridin-2-yl]oxy}-2,2-dimethylpropionic acid 3-{[5-(4-{[(2-ethylphenyl)amino) Methyl hydrazino]amino phenyl) hydrazine tert-yl-2-yloxy}-2,2-dimethylpropionic acid. (XXX) A further aspect of the present invention provides the heteroarylbenzene compound described below, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, -21 - 200918053 1-({[5-(4-{[(2,4-Dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]amino}methyl) ring Propanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chlorophenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]amino}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(2,4-dimethylphenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔 5-(4-{ 〔(2,4-Dimethylphenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylate Acid 1-( { 〔5-(4-{[(3,5-dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylate Acid 1-[ ( {5-[4-( { [2-methoxy-5-(trifluoromethyl)] Phenyl]aminomethylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1- ( { 〔5-(4-{[(2,3-dimethyl) Oxyphenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2-chlorophenyl) Aminomethylamino]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-ethylphenyl)amino) Methylamino]amino}phenyl)pyridin-2-yl]oxanylmethyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2-methoxy-5-methylphenyl) Aminomethylmercapto]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid. (XXXI) Another aspect of the present invention provides the -22-200918053 heteroarylbenzene compound described below, a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvent thereof Compound, 1-( { 〔5-(4-{ 〔(2-chloro-4-fluoro-5-methylphenyl)aminomethylindolyl)amino}phenyl)pyrimidin-2-yl]oxy} Methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethane)amino}phenyl)pyrimidin-2-yl]oxy }Methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-phenyl)aminomethyl]amino}phenyl)pyrimidin-2-yl] Oxygen}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chlorophenyl)aminomethylindenyl)amino}phenyl)pyrimidin-2-yl]oxy}A 1-( { 〔5-(4-{ 〔(2-fluoro-5-methylphenyl)aminomethylindolyl)amino}phenyl)pyrimidin-2-yl]oxy }Methyl)cyclobutanecarboxylic acid 1-( { 〔 5-(4-{ 〔(3-chloro-2-fluorophenyl)aminomethylindolyl)amino}phenyl)pyrimidin-2-yl] Oximemethyl)cyclobutanecarboxylic acid 1-[({5-[4-( { [4-methyl-3-(trifluoro]) Phenyl]amino]methylmercapto}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[({5-[4-( { [4-fluoro- 3-(Trifluoromethyl)phenyl]aminomethylindenyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ [(4-Chloro-3-methoxyphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-( 4-{[(3-chloro-4-methoxyphenyl)aminomethyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-C ( { 5-[ 4-( { 〔 3-(Proton-2-yl)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid-23 - 200918053 1- 〔( { 5- 〔 4-( { 4-fluoro-2-(trimethyl)amino)phenyl]pyrimidin-2-yl}oxyl 1-[({5-[4-( { 〔2-per-5-(didecyl}amino)phenyl]pyrimidin-2-yl}oxyl 1- [( { 5- 〔 4-( { 〔 2-methyl-5-(methyl fluorenyl) Amino)phenyl]pyrimidin-2-yl} 1-({[4-(4-{[[2-chloro-5-fluorophenyl)phenyl)pyrimidin-2-yl]oxy}methyl)) 1- 〔 ( { 5- 〔 4- ( {[3-(Trifluoromethyl}amino)phenyl]pyrimidin-2-yl}oxy) 1-[({ 5-[4-({[4-(trifluoromethyl)amino)phenyl) Pyrimidine-2-yl}oxy) 1-( { 〔5-(4-{ 〔(3-carbyl))pyrimidin-2-yl]oxy}methyl)cyclopropane 1- ( { 〔 5- (4- { 〔(3-chloro-4-methoxyamino}phenyl)pyrimidin-2-yl]oxy}methyl 1-( { 〔5-(4-{ 〔 (3 - chloro-4 - truncated) Benzyl)pyrimidin-2-yl]oxy}methyl)cyclo 1-( { 〔 5-(4-{ 〔(2-fluoro-5-methyl}phenyl)pyrimidin-2-yl)oxy }methyl) 1-[(丨5-[4-({[4-fluoro-3-(trimethyl)amino)phenyl]pyrimidin-2-yl}oxyl 1-[( { 5- 〔 4 - ( { [4-fluoro-2-(trimethyl)amino)phenyl]pyrimidine-2-yl}oxyfluoromethyl)phenyl]aminomethyl,)methyl]cyclobutanecarboxylic acid fluoride Phenyl]amino]aminomethyl)methyl]cyclobutanecarboxylic acid trifluoromethyl)phenyl]aminooxy)methyl]cyclobutanecarboxylic acid)aminocarbamoyl]aminobutanecarboxylate Acidoxy)phenyl]aminocarbazinylmethyl]cyclobutanecarboxylic acid oxy)phenyl]aminocarboxamidinemethyl]cyclopropanecarboxylic acid amine formazan Amino}phenylcarboxylic acid phenyl)aminocarbazinyl])cyclopropanecarboxylic acid)aminocarbamoyl]aminopropanecarboxylic acid phenyl)aminomethylmercapto]amine cyclopropanecarboxylic acid fluoride Methyl)phenyl]aminomethyl)methyl]cyclopropanecarboxylic acid fluoromethyl)phenyl]aminomethyl)methyl]cyclopropanecarboxylic acid-24- 200918053 l-[ ( {5-[ 4-( {[2-Fluoro-5-(trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1- [ ( {5 -[4-( { 〔3-(Trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[ ( {5-[4-( { 〔4-methyl-4-(trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclo Propanecarboxylic acid 1-[({5-[4-({[2-chloro-4-(trifluoromethoxy)phenyl]aminomethyl)amino)phenyl]pyrimidin-2-yl} Oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-(){[2-(trifluoromethoxy)phenyl]aminocarbamoylamino)phenyl]pyrimidine-2 -yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 2-(2-chloro-4-fluorophenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2-Fluoro-5-methylphenyl)aminomethylmercapto]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1-(丨[5-(4-丨[(2-Chloro-4-fluorophenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid sodium 1-[ ({5-[4 -( { 〔2-fluoro-5-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( {[5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1- ({[5-(4-{ 〔(5-Chloro-2-fluorophenyl)aminomethylindolyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1 -( { 〔5-(4-{ 〔(2-Chloro-5-fluorophenyl)aminocarbamoyl)amino-25- 200918053 }phenyl)pyridin-2-yl]oxy}methyl) ring Butanecarboxylic acid 1-[({5-(4-({[3-(trifluoromethoxy)phenyl]aminomethyl)amino)phenyl]pyridin-2-yl}oxy) Cyclobutanecarboxylate 1-[({5-[4-( { 〔4-fluoro-2-(trifluoromethyl)phenyl)aminocarbinylamino)phenyl]pyridin-2-yl}oxy)methyl 】 cyclopropanecarboxylic acid 1-[({5-(4-( { 〔4- gas- 2-(di-homylmethyl)phenyl)aminocarbinyl)amino)phenyl]pyridin-2-yl }Oxo)methyl]cyclopropanecarboxylic acid 1-[({5-[4-({[2-chloro-4-(trifluoromethyl)phenyl]aminomethylindenyl)amino)phenyl] Pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[( { 5- [ 4-( { 〔4-fluoro-3-(trifluoromethyl)phenyl]aminomethylindenyl)amine Phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-(({ 5-[4-({[2-(trifluoromethoxy)phenyl))aminomethyl) Amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-fluorophenyl)aminocarbinyl) Amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-[({5-[4-( { 〔2- gas-4-(dimethoxymethoxy)phenyl) Aminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-( { [2-methyl-4-(3) Fluoromethoxy Phenyl]aminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-( { [3-(trifluoromethoxy) Phenyl]aminomethylaminomethyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1- { 〔( 5- { 4-[(cyclohexylaminocarbazide) Amino]phenyl]pyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid -26- 200918053 l-[ ( {5-[ 4-( { [2-fluoro- 5-(trifluoromethyl) Phenyl]amino]methylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-( { [4-(trifluoro]) Methoxy)phenyl]aminomethylmercapto}amino)phenyl]pyran-2-yl}oxy)methyl]cyclopropane phthalic acid 1- ( { 〔5-(4-{[(2 ,4-dimethylphenyl)aminocarbamimidylamino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔 2-(4-phenyl-4-amino)alkylamino]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2-Fluoro-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1- ({[5-(4-{[(2,4-Dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclohexanecarboxylic acid 1 -( { 〔5-(4-{ 〔(2-Ethoxy-4-ylamino)aminomethylsodium)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclohexanecarboxylic acid 1-[({5-[4-({[4-(2-(2-methyl)phenyl)aminomethyl)amino)phenyl]pyridin-2-yl}oxy)methyl Sodium cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(4-fluoro-3-methylphenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]oxy }Methyl)Sodium cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(2-bromo-5-methylphenyl)aminocarbamoyl)amino}phenyl)pyridine-2- Sodium oxy)methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(2- gas-4-per-5-methylphenyl)aminocarbazyl)amino}phenyl Sodium pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-[({5-[4-({[[3-(trifluoromethyl)phenyl]aminomethyl)amino) Sodium phenyl]pyridine-2-yl}oxy)methyl]cyclobutanecarboxylate -27- 200918053 1- [ ( {5-[ 4-( { 〔4-chloro-3-(trifluoromethyl)) Phenyl]aminocarbamyl} Sodium (phenyl)pyridin-2-ylindoleoxy)methyl]cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(2-fluoro-5-methylphenyl)aminocarbamidine) Sodium]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(3-methylphenyl)aminocarbinyl) Amino} phenyl)pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid sodium 1-[({5-[4-( { 〔2-chloro-4-(trifluoromethoxy)) Phenyl]aminomethylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate sodium ([5-[4-( { [2-methyl- 4] -(Trifluoromethoxy)phenyl]aminocarbamimidoamino)phenyl]pyridin-2-ylindoleoxy)methyl]cyclobutanecarboxylic acid sodium 1-( { 〔5-(4 -{[(2,5-Dichlorophenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium 1-( { 〔5-( 4-{[(3-Chlorophenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium 1-({[5-(4- {[(3,5-Dichlorophenyl)aminomethylindolyl]amino}phenyl)pyridine-2 ·yloxy]methyl)cyclobutanecarboxylic acid sodium 1-( { 〔5-(4 -{ 〔 (3 -chloro-4-methoxyphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium 1-( { 〔5-(4- {[(4-Cyano-2-methylphenyl)aminocarbamimidyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium 1-( { [5 -(4-{ 〔(3-chloro-2-fluorophenyl)aminocarbamimidyl)amino}phenyl)pyridinyloxy}methyl)cyclobutanecarboxylic acid sodium-28- 200918053 1- ( { 〔 5-(4-{ 〔(4-tert-butylphenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1- [({5-[4-({[2-Methyl-5-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl] Sodium cyclobutanecarboxylate 1-[({5-[4-({[[3-(propan-2-yl)phenyl]aminomethyl)]amino)phenyl]pyridin-2-yl}oxy Sodium methyl]cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(4-chloro-3-methoxyphenyl)aminocarbamoyl)amino}phenyl)pyridine-2 Sodium 1-({[-(4-{[(2,2-difluoro-1,3-benzodioxin-5-yl))) Hyperthyroidism Sodium]amino]phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-[({5-[4-( { 〔4-methyl-3-(trifluoromethyl))) Sodium phenyl]aminomethyl hydrazino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate 1- [ ( {5-[4-( { 〔2-chloro- 5 -(Trifluoromethyl)phenyl]aminomethylmethyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate 1-[({5-[4-( {[4-Cyano-3-(trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate 1-( {[5-(4-([2,4-Dimethylphenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylate. (XXXII) Another aspect of the present invention provides the heteroarylbenzene compound described below, a tautomer of the compound, a stereoisomer, -29-200918053 or a pharmaceutically acceptable salt thereof or a solvent thereof Compound, 1-( { 〔5-(4-{ 〔(2- gas-4-perphenyl)aminomethyl]amino}-3-fluorophenyl)pyrimidin-2-yl]oxyguanidine 1-({[-(4-{[(2-chloro-5-fluorophenyl)aminomethylindolyl]amino}-3-fluorophenyl)pyrimidin-2-yl) 1-[(5-[3-fluoro-4-({[[fluoro]-2-(trifluoromethyl)phenyl]aminocarboxamyl)} Amino)phenyl]pyrimidin-2-ylindoleoxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(3-fluoro-4-{ 〔(2-fluoro-5-methylphenyl)) Aminomethylmercapto]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2- gas-4-phenyl) Aminomethyl]amino}-3,5-difluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2 -chloro-4-fluorophenyl)aminomethylindolyl]amino}-3-fluorophenyl)pyridin-2-yl]oxy}methyl) ring Alkylcarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethylindenyl)amino}-2-fluorophenyl)pyridin-2-yl]oxy} Methyl)cyclobutanecarboxylic acid 1-( { 〔5-(2-chloro-4-{ 〔(2-chloro-4-fluorophenyl)aminocarbamoyl)amino}phenyl)pyridine-2 1-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethylindenyl)amino} -2-methyl Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-5-fluorophenyl)aminomethylindenyl)amine }-3-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[3-fluoro-4-( { [2-fluoro- 5-(trifluoro]) Methyl)phenyl]aminomethylindenyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxy-30- 200918053 Acid 1_ ( { 〔 5_ ( 3-fluoro-4- { 〔(2-Fluoro-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxanylmethyl)cyclobutanecarboxylic acid 1_( { [5-(4 -{[(2_Chloro-5-fluorophenyl)aminomethylindenyl]amino}-2-fluorophenyl)pyridin-2-indoleoxy}methyl)cyclobutanecarboxylic acid 1-[ ( { 5-[ 2-Fluoro-4- ( { 〔 2_气_5 _ (Trichloromethyl)phenyl]aminomethylmercapto}amino)phenylhydrazine] ω1 D定_2_yl}oxy)methyl]cyclobutane hydrazine 1-({[5-(2 -Chloro-4-indole [(2_chloro-5-fluorophenyl)aminomethylindenyl]amino}phenyl)pyridin-2-indoleoxy}methyl)cyclobutanecarboxylic acid [({ 5-[2-Chloro-4-({[2_fluoro_5-(triple methyl)phenyl]aminocarbinyl)amino)phenyl)]pyrosin-2-yl}oxy)methyl Cyclobutanecarboxylic acid 1_( { 〔5_(4_{ 〔(2-chloro-4-fluorophenyl)aminomethyl]amino} _2,5-difluorophenyl)pyridine-2-yl] Oxyquinomethyl)cyclobutanecarboxylic acid. (XX X111) Another aspect of the present invention provides the heteroarylbenzene compound described below, a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof -( {5-[4-( { chloro-3-(trifluoromethyl)phenyl)-phenylamino)phenyl]pyrimidin-2-yl}oxy)-2,2-dimethyl 3-propionic acid 3-{[5-(4-{[(3,4-)-chlorobenzyl]amino)phenyl) benzyl-2-yloxy] _2,2-methylpropane Acid 2,2-dimethyl-3-( {5-[4-({ 〔3-(trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyrimidine 11 _2 丨 丨 丨) Propionic acid-31 - 200918053 2.2-Dimethyl- 3-({5-[4-({[3-(trifluoromethoxy)phenyl)carbonyl]amino)phenyl]pyrimidin-2-yl} Oxygen)propionic acid 3-{[5-(4-{[(3-chloro-4-methylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}-2,2-dimethyl 3-( {5-[4-( { 〔4-chloro-3-(trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyridin-2-yl}oxy)-2,2 _Dimethylpropionic acid 3- {[ 5-(4- {[(3-oxo-4-methylphenyl)indolyl]amino}phenyl)pyridin-2-yl]oxy} -2,2- Dimethylpropionic acid 3-{ [5-(4-( (3,4 - _ phenyl) yl)amino}phenyl)pyridin-2-yl]oxy} -2,2-dimethyl Propionate 2.2-dimethyl-3-({5-[4-({[3-(trifluoromethyl)phenyl)carbonyl)amino)phenyl)pyridin-2-yl}oxy)propane Acid 2.2-Dimethyl-3-({5-[4-({[3-(trifluoromethoxy)phenyl)carbonyl)]amino)phenyl]pyridin-2-yl}oxy)propanoic acid. (XXXIV) Another aspect of the present invention provides the heteroarylbenzene compound described below, a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, 1- [({5-[4-( { 〔3-(Trifluoromethoxy)phenyl)carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( {[5-(4-{ 〔(3-Chloro-4-methyl-benzyl)indolyl}amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid [(5 -[4-( { chloro-3-(trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[ ( {5-[4-( { 〔3-(Trifluoromethyl)phenyl)carbonyl}amino-32- 200918053 )phenyl] 1-( {-(4-{ 〔(3,4-dichlorophenyl)carbonyl)amino}phenyl)pyrimidine-2-(pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[[5-{4-[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyrimidine-2 -yl)oxy]methyl}cyclobutanecarboxylic acid 1-[({5-[4-({[3-(propyl-2-yl)phenyl)indolyl)amino)phenyl]pyrimidine- 2-(yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-methoxyphenyl)carbonyl)amino}phenyl)pyrimidine-2 1-[()-[4-(4-({[3-(trifluoromethoxy)phenyl]carbonyl)amino)phenyl]pyrimidin-2- 1-( { 〔5-(4-{ 〔(4-fluoro-3-methylphenyl)carbonyl)amino}phenyl)pyrimidin-2-yl]oxy }methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-methylphenyl)carbonyl)amino}phenyl)pyrimidin-2-yl]oxy}methyl Cyclopropanecarboxylic acid 1-[({5-[4-({[4-chloro-3-(trifluoromethyl)phenyl)carbonyl)amino)phenyl]pyrimidin-2-yl}oxy)) Cyclopropanecarboxylic acid 1-[ {5-[4-( { 〔3-(Trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5- (4-{ 〔(3,4 - __Chloryl) yl)amino}phenyl)pyrimidin-2-yl]oxanylmethyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ [(3-ox-4-perphenyl) ortho]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3 ,4-dimethylphenyl)carbonyl]amino}benzene-33- 200918053 yl)pyrimidin-2-yl]oxaniummethyl)cyclopropanecarboxylic acid 1-{[(5-{4-[(5, 6,7,8-tetraxan-2-ylindenyl)amino]phenyl}pyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylic acid 1-[ ( {5-[4-( { 〔 3-(propan-2-yl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3 - Gas-4-methoxyphenyl)indenyl]amino}phenyl)pyrimidine-2-yloxy}methyl)cyclopropanecarboxylic acid 1-[({5-[4-( { 〔3-( Trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔 (4 - gas-3) -methylphenyl)indenyl] Amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-fluoro-4-methylphenyl)carbonyl)amino Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-( { 〔4- gas-3-(dimethylmethyl)phenyl)) } Amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3,5-difluorophenyl)carbonyl)amino} Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-({[5-(4-{[(2,2-difluoro-1,3-benzodioxin-5) -yl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-C ( { 5- [ 4- ( { [2-methoxy- 3- (three) Fluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid [(5-[4-( { [2-methoxy-5] -(Trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[ ( {5-[4-( { [3- Trifluoromethoxy)phenyl]carbonyl}amine-34- 200918053 phenyl)pyridin-2-ylindoleoxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 3-chloro-4-methylphenyl Carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[ ( {5-[4-( { 〔3-(1,1,2,2-four) Fluoroethoxy)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (4-methoxy) 3-(methylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-({[5-(4-{[(3,4-) Ethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-( { 〔3-fluoro-4-(three) Fluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1- ( { 〔 5- ( 4- { 〔 ( 3-chlorophenyl) Carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-({[3-(trifluoromethyl)phenyl)carbonyl)} Amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3,5- _)))] Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid [(5-[4-({[4-(trifluoromethoxy)phenyl)carbonyl)amino)phenyl) Pyridine-2- Oxa)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-methoxyphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl Cyclobutanecarboxylic acid ({[5-(4-{[(3-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1 -( { 〔5-(4-{ 〔(3,4-Dichlorophenyl)carbonyl)amino}phenyl-35- 200918053 )pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1 - { [ 5-{4-[(naphthalen-2-ylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid { [5-(4-{ 〔 ( 3-aromatic 4-ring (base) curtain group]amino}phenyl)pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3 , 4-dimethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1- ( { 〔5-(4-{ 〔 (4-B Phenyl)carbonyl]amino}phenyl}pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[( { 5- [ 4- ( { [4-methyl- 3- (three) Fluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1- { 〔( 5- { 4-[(biphenyl-3-ylcarbonyl) Amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3,5-dimethylphenyl)carbonyl)amino} Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3 -methoxy-4-methylphenyl)indolyl)amine Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-methoxyphenyl)carbonyl)amino} Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(4-chloro-3-methylphenyl)) yl}} benzene 1-(pyridin-2-yl)oxy}methyl)cyclobutanecarboxylic acid 1-{[(5-{4-[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino] Phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid 1-[({5-[4-( { 〔3·(propan-2-yl)phenyl)carbonyl)amino-36 - 200918053 )Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[( { 5-[ 4-( { -3-(methylsulfanyl)phenyl)carbonyl)amine Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[({5-[4-({[4-chloro-3-(trifluoromethyl)phenyl)carbonyl) } Amino)phenyl Pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-cyanophenyl)carbonyl)amino}phenyl)pyridin-2-yl] Oxygen}methyl)cyclobutanecarboxylic acid 1-[({5-[4-({[3-(trifluoromethoxy)phenyl)carbonyl)amino)phenyl]pyridin-2-yl}oxy) )methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(4-fluoro-3-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl Cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropane 1-[(5-[4-({[[chloro]-3-(trifluoromethyl)phenyl)carbonyl)]amino)phenyl]pyridin-2-yl}oxy)methyl]] Propanecarboxylic acid 1-[({5-[4-({[3-(trifluoromethyl)phenyl)carbonyl)amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3,4 - chlorophenyl))]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { [5-(4-{ 〔(3,4-Dimethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxaniummethyl)cyclopropanecarboxylic acid 1-( { [5- (4-{ 〔(3-chloro-4-fluorophenyl)carbonyl)amino phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-{ 〔 (5-{4-[ (5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]benzene-37-yl} i- c )benzene 1-(phenyl 1-[ )benzene or its 1-[amine Base 1-[Amino compound or medically improved medicinal agent 200918053 pyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid ({ 5-[ 4- ( { 〔 3-(propan-2-yl) Phenyl]carbonyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid { [5-(4-{ 〔(3-chloro-4-methoxyphenyl)carbonyl)pyridine-2-yl Oxy}methyl)cyclopropanecarboxylic acid ({5-[4-({[3-(trifluoromethyl)phenyl)carbonyl]pyridin-2-yl}oxy)methyl]cyclopentanecarboxylic acid. (XXXV) Another embodiment of the present invention provides the following basic benzene compound, a tautomer of the compound, a sterically pharmaceutically acceptable salt or a solvate thereof, ({5-[3-fluoro-4-({ [3-(Trifluoromethyl)phenyl)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid ({5-[3-fluoro-4-({[3-(trifluoro)) Methyl)phenyl)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (XXXVI) Another embodiment of the present invention, a pharmaceutical, as described in any one of (XXXV) A tautomer, a stereoisomer, or a pharmaceutically acceptable solvate thereof is used as an active ingredient. (XXXVII) Another aspect of the invention, (XXXVI, for use in the prevention or treatment of a disease or condition which is inhibited by D GAT 1 (XXXVIII), another aspect of the invention, (XXXVII drug, which is obesity, Hyperlipidemia, high triglyceride, abnormal disease, diabetes, atherosclerosis, or fatty acid, amine, amine Hyperemia, hypertriglyceridemia, hypertriglyceridemia, abnormal lipid metabolism, diabetes, arteriosclerosis caused by blood stasis and fatness caused by the inclusion of the compound and the salt of the permissibility -38-200918053 Prevention or treatment of hypertension or hypertension. [Effects of the Invention] According to the present invention, a compound having an excellent DGAT1 inhibitory action can be provided. [Best Mode for Carrying Out the Invention] Hereinafter, the present invention will be described in detail, but it is not particularly limited to those listed. In the present invention, 'η' means positive, "i" means different, "5" means second 't', or "tert" means third, "c" means ring, "〇" means neighbor, "m" Between the representations, "P" means right. The meaning of "C!_3 alkyl" means a linear or branched network having 1 to 3 carbon atoms; for example, methyl, ethyl, η-propyl, i-propyl, The methyl group is preferred. The meaning of "C^-6 alkyl J" means a linear or branched alkyl group having 1 to 6 carbon atoms; and examples thereof include a methyl group, an ethyl group, an η-propyl group, and an i-propyl group. , η-pentyl ' η-hexyl, i-butyl, t-butyl, s-butyl, i-pentyl, preferably methyl. "C i -8 alkyl" means a linear or branched alkyl group of 1 to 8 carbon atoms; for example, methyl, ethyl, η-propyl, η-butyl, η-pentyl, η-hexyl, η-heptyl, η - octyl' i-propyl, butyl, t-butyl, s-butyl, i-pentyl, neopentyl, t-pentyl, methyl, ethyl, i--39- 200918053 propyl T-butyl is preferred. The meaning of "Cnocycloalkyl J" means a cyclic alkyl group having 3 to 10 carbon atoms; and examples thereof include a cyclopropyl 'cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. The adamantyl group is preferably a cyclohexyl group. The meaning of "halogen atom" means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and a fluorine atom or a chlorine atom is preferred. The meaning of "0^-6 alkoxy" means a linear or branched alkoxy group having 1 to 6 carbon atoms; and examples thereof include a methoxy group, an ethoxy group, and an n-propoxy group. , i-propoxy, η-butoxy, i-butoxy, s-butoxy, t-butoxy, η-pentyloxy, i-pentyloxy, η-hexyloxy, The methoxy group is preferred. The term "di((6)alkyl)" means an amine group having the same or different "C! -6 alkyl group" as a substituent; for example, a dimethylamino group, Diethylamino, di-η-propylamino, di-i-propylamino, di-i-butylamino, di-s-butylamino, di-t-butylamino Ethyl (methyl)amino group, methyl (η-propyl) amine group. "q. 6 alkylthio group" means a linear or branched chain having 1 to 6 carbon atoms. The alkylthio group; for example, methylthio, ethylthio, η-propylthio, i-propylthio, butylthio, i-butylthio, s-butylsulfide a base, a t-butylthio group, preferably a methylthio group. "Ci-6 alkylsulfonyl" means a straight or branched alkyl group having 1 to 6 carbon atoms. Sulfhydryl group; for example, methylsulfonyl, ethylsulfonyl, η-propylsulfonyl, i-propylsulfonyl, η-butylsulfonyl, i-butylsulfonyl , s-butylsulfonyl, t-butylsulfonyl, preferably methylsulfonyl. -40- 200918053

The meaning of "Cl-8 alkyl" means a linear alkyl group having 1 to 8 carbon atoms; for example, methyl, ethyl, propyl, butyl, pentyl It is preferred to stretch methyl, extend ethyl, and extend propyl. The meaning of "perylene group C, · 6 alkyl group" means "c ! -6 fluorenyl group" having a hydroxyl group as a substituent: for example, a transmethyl group, a 2-alkyl group, a 3-amino group- Η-propyl '2-hydroxy-η-propyl, 4-hydroxy-η-butyl, 2-hydroxy-i-propyl, preferably hydroxymethyl. The term "heterocyclic ring of 5 to 7 members" means a 5- to 7-membered ring monocyclic saturated heterocyclic ring formed by one halogen atom and 4 to 6 carbon atoms: for example, a pyrrolidine ring The piperidine ring and the high piperidine ring are preferably a pyridinium ring or a pipe steep ring. The term "naphtholine of 3 to 6 members" means a cyclic alkyl ring having 3 to 6 carbon atoms; and examples thereof include a cyclopropane ring, a cyclobutyl ring, a cyclopentazol ring, and a cyclohexane.兀is ' is a ring of C; ^兀ί哀, 环丁院环,环环院环, preferably "3 to 6 members of the heterocyclic ring" means one oxygen atom and 2 to 5 The monocyclic saturated heterocyclic ring of a 3- to 6-membered ring formed by a carbon atom may, for example, be an oxirane ring, an oxetane ring, a tetrahydrofuran ring, a tetra-pyran ring, or a tetrahydropyran ring. Preferably. Preferred embodiments of the compound of the present invention are as follows. That is, 'R1 is preferably a hydrogen atom, a methyl group or an ethyl group, and Ri is more preferably a hydrogen atom. R2a is preferably a hydrogen atom, a chlorine atom, an oxygen atom, or a methyl group. R2b is preferably a hydrogen atom, a chlorine atom or a fluorine atom. -41 - 200918053 r2 is preferably a hydrogen atom, a halogen atom or a methyl group, and R2 is more preferably a hydrogen atom, a chlorine atom, a fluorine atom or a methyl group. Q is preferably a substituted phenyl group having the same or different 1 to 3 groups of a group of (8, an alkyloxy group, a trifluoromethyl group, a trifluoromethoxy group, and a halogen atom). Preferably, -〇-, or -NR3-, X more preferably represents -〇-. R3 is preferably a hydrogen atom. m is preferably 1»η is preferably 0, or 1. Υ is preferably a formula (D) -1), formula (D-2), formula (D-3), formula (D-4), or formula (D-5) [Chemical 1 3]

(Dl) (D-2) (D-3) (D-4) (D·5) The base represented by (D-2), (D-3), and (D-4) ) or the base represented by the formula (D-5). In the present invention, the meaning of the pharmaceutically acceptable salt may, for example, be a mineral acid salt such as a hydrochloride, a hydrogen bromide, a hydrocyanate, a phosphate, a sulfate or a nitrate; for example, methanesulfonic acid Salt, ethanesulfonate, benzenesulfonate, p-toluenesulfonate sulfonate; such as oxalate, tartrate, citrate, maleate, succinate, acetate, benzene a carboxylate of a formate, mandelate, ascorbate, lactate, gluconate, malate; such as glycinate, lysinate, arginine, alanate, glutamine Acid salt, -42- 200918053 Amino acid salt of aspartate; or inorganic salt such as lithium salt, sodium salt, potassium salt, calcium salt, magnesium salt or as with ammonium salt, triethylamine salt, two The salt of an organic base of an isopropylamine salt or a cyclohexylamine salt is preferably a hydrochloride, a hydrogen bromide, a phosphate, a sulfate, a methanesulfonate, a P-toluenesulfonate, or an oxalic acid. Salt, tartrate, citrate, acetate, lactate, glutamate, aspartate, sodium, potassium, ammonium or triethylamine. The meaning of the solvate in the present invention means a pharmaceutically acceptable solvate of the compound of the present invention or a salt thereof. The compound of the present invention and a salt thereof may be hydrated or adsorbed by exposure to air or recrystallized, or may be hydrated; and the hydrate of the present invention is also contained in the compound of the present invention. . The compounds of the present invention have asymmetric centers, in which case various optical isomers are present. Therefore, the compound of the present invention may contain (+) a body (monomer), a (-) body (monomer), a racemate or a (±) mixture of two optically active substances in an arbitrary ratio, and further has two In the case of the above asymmetric center compound, the non-corresponding isomers which are produced by the respective optical isomers are also present, and the compound of the present invention may contain all of these types in an arbitrary ratio. Non-corresponding isomers Those skilled in the art can be separated by well-known methods, such as separate crystallization methods, etc. Further, the optically active system can be obtained by a well-known organic chemistry for this purpose. Further, 'the compound of the present invention is a geometric isomer of a cis form, a trans form or the like, and the compound of the present invention contains such an isomer and contains the isomer in an arbitrary ratio. By. The heteroarylbenzene compound of the present invention may be a pharmaceutically acceptable salt thereof, -43-200918053 or a solvate thereof. Hereinafter, the compound of the present invention, a tautomer of the compound, a stereoisomer, a permissible salt or a solvate thereof are referred to as "invention - in addition" with respect to chemically or metabolically decomposable The compound which forms an active compound of the present invention, which is usually referred to as a prodrug, i, is also included in the "compound of the present invention" in the solvolysis or physiological conditions. The compound of the present invention has a D G AT 1 inhibitory action, and the compound can correct obesity by inhibiting the production and accumulation of trisium in the small intestine and/or adipose tissue. Therefore, the existing obesity means that the inventive compound which can be utilized as a different mechanism of action is a secretion of a malignant physiologically active substance (adipocyte factor) which is inhibited by inhibiting the hypertrophy of fat cells. A therapeutic drug for diabetes with improved insulin resistance. Diabetes includes type 1 diabetes, type 2 diabetes, and other causes for other types of diabetes. Further, the compound of the present invention is resistant to ketoacid vasculopathy (retinopathy, nephropathy), arteriosclerosis (sclerosing disease, myocardial infarction, cerebral infarction, peripheral arterial disease, etc.) (sensory nerve, motor nerve, autonomic nerve, etc.), The treatment and prevention of diabetic complication such as athlete's foot disease is also effective. Further, the compound of the present invention can be combined with the anti-obesity agent, the diabetes therapeutic agent, the diabetes therapeutic drug, the hyperlipidemia therapeutic drug, the hypertensive therapeutic drug, etc., which are inhibited by DGAT1 from acting differently, by combining the compound of the present invention with Other pharmaceutical agents, the above-mentioned hexaarylbenzene or its pharmaceutical compound j. In addition to the disease, microbes, atherosclerosis, dysplasia, infection, etc. The syndrome is used. In the disease, the effect of each single agent is higher than that of -44-200918053, and it is expected to have a synergistic effect when used. As an anti-obesity drug, a therapeutic drug for diabetes, and a treatment for diabetes complications The medicine may, for example, be a norepinephrine, a dopamine, or a serotonin (Serotonin), and then take an inhibitor (for example, mazindol) or serotonin (for example, fenfuramin). , β3-capacity agonist (eg, BRL2683 0 A), orthotropin (Norepinephrine), serotonin (Serotonin) and then take in the obstruction drug (eg, Sibutramine), pancreatic fat sputum (pancreatic) Lipase) inhibitors (eg, Orlistat), cannabinoids, and antibiotics (eg, Rimonabant, MK-0364, Taranabant ' CP-94 5 5 9 8 ), melanin agglutination hormone Capsule antibiotics (eg, 856464, AMG-076, NGD-4715), insulin preparations, insulin resistance improving drugs (ΡΡΑΙΙγ-excited, PPARa/γ-excited, ΡΡΑΙΙδ-excited, PPARa/γ/δ-excited, etc.) (Example, pioglitazone, rosiglitazone, GW-501516, GW-5 9073 5, AB T-3 3 5, AZ D - 6 6 1 0, AVE - 8 1 3 3), a glucosidase inhibitor (eg, voggliose, acarbose, Mi gl ito 1 ), biguanides ( For example, Metformin, Buformin, Phenformin, insulin secretion promoting drugs (eg, Glibenclamide, Glimepiride, Repaglinide) ), sugar release ( nateglinide), mitiglinide (Mitiglinide), membrane blood glucose -45- 200918053

Receptor antagonist, insulin receptor kinase promoting agent, dipeptidyl peptidase IV inhibitor (eg, vildagliptin, TS-021, sitagliptin, BMS-477 1 1 8 ), SGLT inhibitors (eg Sergliflozin, dapagliflozin, KGT-1681, YM543, TS-03 3, AVE-2268,), PTPlb inhibitors (eg, sodium vanadate), glucose 6 phosphatase inhibitors, glycosylphosphatase (glycogen phosphorylase) inhibitors (eg, PSN-357, FR-25 8900), FBPase inhibitors (eg, MB-07803), PEPCK inhibitors, pyruvate dehydrogenase kinase inhibitors, D-hexaphosphate inositol ( D-chiro-inositol), GSK 3 inhibitor, GL P -1 excimer (eg, liraglutide), aldehyde resin alcohol (eg, Pramlintide), Glucocorticoid receptor antagonist, llBetaHSD1 inhibitor ( Examples, AMG-221, INCB-13739), protein kinase C inhibitors (eg, ruboxistaurin), Beta3 adrenaline (

Adrenalin) receptor extract (eg, AJ·9677), phospholipidinositol kinase inhibitor, phosphatidylinositol discase inhibitor, ACC inhibitor, GPR40 receptor, GPR1 19 Receptor excitons (eg, APD-66 8 ), TGR5 receptor complexes, AMPK activators (eg, DRL-16536), Aldose (aldose) reductase inhibitors, AGE inhibitors, glucokinase (Glucokinase) Activated drugs, etc. In addition, as a medicament for the diabetes-related diseases which can be used, HMG-CoA reductase inhibitor, squalene synthetase inhibitor, bile acid sorbent, 1B A τ inhibitor, c ETP inhibitor, CP τ hinder Medicine, -46 - 200918053 Fibrate, Fibrate, ACAT, MGAT, DGAT, cholesterol absorption inhibitor, Μτρ inhibitor, nicotinic acid inducer, LXR, LDL Receptor-promoting drug, angiotensin-converting enzyme inhibitor, angiotensin II antagonist, angiotensin-induced plasmin inhibitor, diuretic, anti-drug, endothelin transforming enzyme inhibitor Endothelin (en doth el in ) is a receptor antagonist, a uric acid production inhibitor, a uric acid excretion promoting drug, and the like. The compound of the present invention can be administered alone or in combination with a pharmaceutically or pharmaceutically acceptable carrier or diluent. When the compound of the present invention is used as a DGAT1 inhibitor, the compound of the present invention can be administered orally or parenterally. Investment can also be. Further, 'administration of a compound containing the compound of the present invention as an active ingredient may be carried out orally or parenterally; for parenteral administration, intravenous administration, nasal administration, transdermal administration, Subcutaneous administration, intramuscular administration, and sublingual administration. The dose of the compound of the present invention varies depending on the administration target, the administration route, the target disease, the symptoms, and the like. However, for example, when an oral administration is administered to an adult patient, the amount of the compound is usually about 0.01 to 100 mg/kg body weight. Preferably, it is 0.05 to 30 mg/kg body weight', more preferably 0.1 to 10 mg/kg body weight, and it is desirable to administer this amount once every 3 times to 3 times. The compound of the present invention can be synthesized by the method shown below. However, the following production methods are examples of general production methods, and are not limited to the production method. Scheme 1 : Method for producing a compound of the invention (1 - g -47 - 200918053 ) from compound (1 - a )

g, N Step (1-1) q>s^N (1-a) (1-b)

O Y from OH

(1-f)

R2

(1-g) (In the scheme, R2a, R2b, Q and Y have the same meaning as defined above, and G and J represent a halogen atom). Step (1 -1): in the solvent, by using the compound (1 - a ), and the formula (1 3 )

(13) The compound represented by Η〇^γΛ^ is reacted in the presence of a base such as sodium hydride to produce a compound (Ι-b). Step (1-2): in the solvent, the formula (1 4 ) can be obtained in the presence of a base (1 - b ), a base such as sodium carbonate, and a palladium reagent such as ruthenium triphenylphosphine palladium. -48- (14) 200918053 〔化1 6〕 or formula (1 5 [化1 7]

OH (four). O2n^^ r R2 gas o2n

The compound represented by 2b (15) is reacted to produce a compound (1-c). Step (1 - 3): in the solvent, the compound (1 - c ) can be reacted under a hydrogen atmosphere, a metal catalyst such as 1% by weight of palladium carbon or 2% of platinum carbon to produce a compound (1). - d ). Further, in the solvent, the compound (1-d) can be produced by reacting the compound (Ι-c) in the presence of iron powder and ammonium chloride water or hydrochloric acid. Step (1 - 4 ) • In the solvent, the compound (1 -d ) and the compound represented by the formula Q-NCO can be reacted in the presence or absence of a base such as triethylamine. The compound (1 -e ) was produced. Further, in the solvent, the compound (1 - d ) can be reacted with a compound represented by the formula Q-NH2 by reacting a 4-nitrophenyl chloroformate in the presence of a base such as pyridine. The compound (1 - e ) was produced. Step (1 - 5): in the solvent, the compound (1-f) can be produced by reacting the compound (1 -e ) in the presence of an acid such as P-toluene, and the like (1-6) In the solvent, the compound of the present invention can be produced by reacting the compound (Ι-f) with an acidifying agent such as chloroperbenzoic acid, etc. -49-200918053

Scheme 2: Production of the compounds (2-e), (2-h), (2-f), (2-g), (2-i), and (2-j) of the present invention from the compound (1-a) Method (chemical 1 8) Ο

(In the scheme, R1, R2a, R2b, Q, X, and Υ have the same meaning as defined above, and J represents a halogen atom, a hydroxyl group or an amine group; and G represents a halogen atom). Step (2-1): a compound represented by the formula HX-Y-COOR1 in which J is a halogen atom, a compound represented by the formula HX-Y-COOR1, or the like, in a solvent such as carbonic acid planer, potassium carbonate or sodium hydroxide. The compound (2-b) is produced by the co-existence or non-coexistence of tetra-n-butylammonium iodide in the presence or absence of a base. Further, when X is -〇-, in the solvent, a compound represented by a compound in which J is a hydroxyl group (Ι-a) and a compound of the formula Hal-Y-COOR1 (wherein Hal represents a spectrin atom) is used in carbonic acid. The compound (2-b) is produced by reacting it in the presence of a base such as a planer. When X is -NH-, the solvent can be represented by the compound (1 - a ) wherein J is an amine group, and the formula HC(=0) -Y'-COOR^C where Y represents a ChT extension-50 - 200918053 Alkyl) acid, etc., such as the basic formula of sodium or the like ([1] or (20)

(17) The hydrogen gas environment is represented by the step of the compound, and the acetal represented by the compound (the compound is represented by the formula ([2, 2]) is reduced with sodium triethoxy hydride hydride, trifluoroethyl The compound (2_b) is produced by amination of a compound (2-2). (2-2): in a solvent, in the presence of a palladium reagent such as a compound (2-b), a carbonic acid, and a triphenylphosphine palladium or the like. Make 16)

The compound (2-c) is produced by reacting OH (16) 17 o 2 N ^ R 2b ί hexahydrate. (2-3): In the solvent, the compound (2-d) can be produced by subjecting the compound (2-c) to a metal catalyst such as 10% palladium carbon or 2% platinum carbon. Further, in the solvent, (2-d) can be produced by reacting 2-0 in the presence of iron powder and ammonium chloride water. (2 · 4 ): in the presence of a palladium reagent such as compound (2 - b ), sodium carbonate, and triphenylphosphine palladium, etc. 8 )

The compound is reacted to produce the compound (2 - d ) -51 - . Further, in 200918053, in the presence of a compound (2-b), a base such as sodium carbonate, and a palladium reagent such as ruthenium triphenylphosphine palladium, the compound (19) can be obtained by the formula (19).

(In the formula 19, a compound represented by L represents a protecting group such as a mercapto group or an ethenyl group) is reacted, followed by deprotection using hydrochloric acid or the like to produce a compound (2-d). Step (2-5): In the solvent, the compound (2-d) and the compound represented by the formula Q-NCO can be reacted in the presence or absence of a base such as triethylamine to produce the present invention. Inventive compound (2-e). Further, in the solvent, the compound (2-d) can be reacted with a compound represented by the formula Q-NH2 by reacting a 4-nitrophenyl chloroformate in the presence of a base such as pyridine. The compound (2-e) of the present invention was produced. Step (2-6): In the solvent, the compound (2-f) of the present invention can be produced by subjecting the compound (2-e) to hydrolysis using a base such as an aqueous sodium hydroxide solution. Step (2-7): In the solvent, the compound (2 g) of the present invention can be produced by forming a sodium salt using the sodium hydroxide aqueous solution or the like of the compound (2-f) of the present invention. Step (2-8): in the solvent, a compound represented by the formula (2-d) and the formula Q-COOH, in dicyclohexylcarbodiimide, 1-(3-dimethylaminopropylpropane In the presence of a condensing agent such as 3-ethylcarbodiimide hydrochloride or 1-hydroxybenzotriazole, in the presence of a base such as triethylamine or diisopropylethylamine, or in the presence of a base of -52-200918053 or The compound of the present invention (2-h) is produced by reacting it in the absence of it. Further, the compound of the present invention (2-h) can be produced by reacting a compound represented by the formula Q-COC1 in the presence or absence of a base such as triethylamine or diisopropylethylamine. ). Step (2-9): In the solvent, the compound (2-i) of the present invention can be produced by subjecting the compound (2_h) to hydrolysis using a base such as an aqueous sodium hydroxide solution. Step (2-10): In the solvent, the compound (2-j) of the present invention can be produced by forming the sodium salt of the compound (2_i)' of the present invention using an aqueous sodium hydroxide solution or the like. Scheme 3: Method for producing the compound (3-f) of the present invention from the compound (1 - a )

I-% (3-d) -R2b (3-e) again

1 (3f) (Q, Ra, R, and Y in the flow chart have the same meaning as described above, and G and J represent halogen atoms). And the step (3 -1): in the solvent, the compound represented by the formula HO-Y-COOCH2Ph can be reacted by the compound (1 _ a ) ' 53 200918053 in the presence of a base such as carbonic acid planing or potassium carbonate. The compound (3-b) was produced. Step (3-2): In the solvent, the formula (2 0) can be obtained in the presence of a base of a compound (3-b), a sodium carbonate or the like, and a palladium reagent such as ruthenium triphenylphosphine palladium. ) [Chem. 24]

Or formula (21) [Chem. 25]

The compound represented is subjected to a reaction to produce a compound (3-c). Step (3-3): In the solvent, the compound (3-d) can be produced by reacting the compound (3-c) in the presence of iron powder and ammonium chloride water or hydrochloric acid. Step (3 - 4 ): in the solvent, by reacting the compound (3 - d ) with 4-nitrophenyl chloroformate in the presence of a base such as pyridine, and then reacting with the formula Q-NH2 The compound shown is subjected to a reaction to produce a compound (3-e). Further, in the solvent, the compound (3 -d) can be reacted with a compound represented by the formula Q-NCO in the presence or absence of a base such as triethylamine to produce a compound (3 - e). Step (3-5): In the solvent, the compound of the present invention -54-200918053 (3-f) can be produced by subjecting the compound (3 - e ) to hydrolysis with a base such as an aqueous sodium hydroxide solution. Scheme 4: Method for producing compounds (4-d) and (4-e) of the present invention from compound (2-b) [Chem. 26]

(2-b) Step (4-1)

OH (in the flow chart, the ruler 1, the ruler 2, (^, \, and 丫 have the same meaning as described above, 〇 represents a halogen atom). Step (4-1): in the solvent, by the compound (2_b), and the carbonic acid In the presence of a base such as sodium, and a palladium reagent such as triphenylphosphine palladium or the like, the formula (22) is [27]

>OH υ The compound represented by (22) is reacted to produce a compound (4-C). Step (4-2): in the solvent, the compound represented by the formula (4-C) and the formula Q-NH2, in dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl) In the presence of a condensing agent such as -3-ethylcarbodiimide hydrochloride or 1-hydroxybenzotriazole, the reaction is carried out in the presence or absence of a base such as triethylamine or diisopropylethylamine. And the compound of the present invention (4-d) is produced in the step (4-3): in the solvent, the compound (4-d) can be used to hydrolyze -55-200918053 with a base such as an aqueous sodium hydroxide solution. The compound of the invention (4-e) is produced. Scheme 5: Process for producing the compound (5-e) of the present invention and the compound (5-f) of the present invention from the compound (5-a) [Chem. 28]

(In the flowchart, R1, Q, R2a, RU, and γ have the same meanings as described above, and 〇 denotes a halogen atom). Step (5-1): In the solvent, the formula Hal-Y-CO OR1 (where Hal represents a halogen atom) can be obtained by the presence of a base of the compound (5-a), a carbonic acid planer, or potassium carbonate. The compound shown is subjected to a reaction to produce a compound (5-b). Step (5-2): in the solvent, the formula (23) can be obtained in the presence of a base (5-b), a base such as sodium carbonate, and a palladium reagent such as ruthenium triphenylphosphine palladium. [29]

Or formula (24 -56- 200918053 [化3 0]

The compound represented is reacted to produce a compound (5-c). Step (5-3): in the solvent, a compound (5-d) can be produced by reacting the compound (5_c)' in a hydrogen atmosphere, a metal catalyst such as 10% palladium carbon or 2% uranium carbon. ). Further, in the 'solvent', the compound (5-d) can be produced by reacting the compound (5 - c ) in the presence of iron powder and ammonium chloride water or hydrochloric acid. Step (5-4): in the solvent, the compound (5-d) can be reacted with 4-nitrophenyl chloroformate in the presence of a base such as pyridine, and then with the formula Q-NH2. The compound represented is reacted to produce the compound (5-e) of the present invention. Further, in the solvent, the compound of the present invention can be produced by reacting the compound (5-d) with a compound represented by the formula Q-NCO in the presence or absence of a base such as triethylamine. 5-e). Step (5-5): In the solvent, the compound (5-f) of the present invention can be produced by subjecting the compound (5-e) of the present invention to hydrolysis using a base such as an aqueous sodium hydroxide solution. Scheme 6: Method for producing (inventive) compound (6-e) from compound (6-a) and compound (6-f) of the present invention -57- 200918053

In the scheme, Q, R2a, R2b, and Y have the same meanings as described above, and G represents a halogen atom). Step (6-1): in the solvent, the compound (6-a) and the formula HC(=0) -Y'-COORx, (where Y' is represented in the above scheme 6 To remove the -CH2- group adjacent to -ΝΗ- (except for the -ΝΗ-upper bond oxygen atom), Rx represents the acetal represented by C!.3 alkyl or benzyl), using triethyl oxime The compound (6-b) is produced by subjecting sodium borohydride, trifluoroacetic acid or the like to reductive amination. Step (6-2): in the solvent, the formula (25) can be obtained in the presence of a base (6-b), a base such as sodium carbonate, and a palladium reagent such as ruthenium triphenylphosphine palladium. 〔化3 2〕

Or formula (26) [chemical 3 3]

The compound represented by -58-200918053 is reacted to produce a compound (6-c). Step (6-3): in the solvent, the compound (6-c) can be reacted in the presence of a metal catalyst such as 1% by weight of palladium carbon or 2% of platinum carbon in a hydrogen atmosphere to produce a compound ( 6-d). Further, in the solvent, the compound (6-d) can be produced by reacting the compound (6-c) in the presence of iron powder and ammonium chloride water or hydrochloric acid.

Step (6-4): in the solvent, the compound (6-d) can be reacted with 4-nitrophenyl chloroformate in the presence of a base such as pyridine, and then with the formula Q-NH2. The compound represented by the reaction is carried out to produce the compound (6_e) of the present invention. Further, in the solvent, the compound (6-d)' can be produced by reacting a compound represented by the formula Q-NCO in the presence or absence of a base such as triethylamine (the present invention). Compound (6_e) 〇Step (6-5): In the solvent, the compound of the present invention (6- can be produced by subjecting the compound (6-e) of the present invention to hydrolysis using a base such as an aqueous sodium hydroxide solution. f). Scheme 7: Production of Compound (7-g) of the present invention, Compound (7-h) of the present invention, Compound (7-丨) of the present invention, Compound η (7-j) of the present invention, from the compound (7-a), The compound of the present invention (7-k), the method of the present compound (7-1)-59-200918053 [Chem. 3 4]

(In the scheme, R1, Q, R2a', R2b, and Y have the same meanings as defined above, and G and J represent a halogen atom; and L represents a protecting group such as a mercapto group or an ethenyl group.) Step (7-1): In a solvent The compound (7-b) can be produced by reacting the compound (7-a) with an acidifying agent such as m-chloroperbenzoic acid, etc. Step (7-2): in the solvent, by the compound (7-b), a compound represented by the formula HO-Y-COOR1 is reacted with a base such as a carbonic acid planer or potassium carbonate to produce a compound (7-c). -60- 200918053 Step (7-3): In the solvent, the compound (7-d) can be reacted in the presence of a metal reagent such as indium or molybdenum hexacarbonyl to produce a compound (7-d). ). Step (7-4): In the solvent, a compound represented by the formula HO-Y-COOR1 can be reacted in the presence of a compound (7-a), a base of a carbonic acid planer, a cesium carbonate or the like to produce a compound (7). - d ). Step (7-5): In the solvent, the formula (27) can be obtained by the presence of a palladium reagent such as ruthenium triphenylphosphine palladium in the presence of a compound (7-d) and a base such as sodium carbonate. 3 5〕

Or formula (28) [chemical 3 6]

The compound represented is subjected to a reaction to produce a compound (7-e). Step (7-6): in the solvent, the compound (7-e) can be reacted in the presence of a metal catalyst such as 10% palladium carbon or 2% platinum carbon in a hydrogen atmosphere to produce a compound (7). -f). Further, in the solvent, the compound (7-f) can be produced by reacting the compound (7-e) in the presence of iron powder and ammonium chloride water or hydrochloric acid. Step (7-7): in the presence of a palladium reagent such as triphenylphosphine palladium or the like in the presence of a compound (7-d), a base such as sodium carbonate, or the like, -61 - 200918053 (29) [Chem. 3 7]

Or formula (30) [chemical 3 8]

P2a OH Χ^τβ^〇η

The compound represented by HgN^^R213 (30) is subjected to (d), and the compound (7-f) is produced. Step (7-8): In the solvent, @@(7_f >, #口口Π疋, etc. in the presence of 'reacted with 4·nitrophenyl chloroformate, and then with the formula Q -ΝΗ2 The compound of the present invention is reacted to produce a compound of the present invention (7-g). Further, in the solvent, the compound (7_f) can be used in the presence or absence of diethylamine or the like, and the formula q_nc The compound of the present invention (7-g) is produced by reacting the compound represented by hydrazine. Step (7-9): In the solvent, the compound (7-g) of the present invention can be used as a base such as an aqueous solution of sodium ammoxide. The compound (7-i) of the present invention is produced by hydrolysis. Step (7-): In the solvent, the sodium salt can be formed by using the sodium hydroxide aqueous solution or the like to form the sodium salt of the compound (7") of the present invention. Inventive compound (7-k). Step (7-1 1 ): In the solvent, the compound represented by the formula (7-f) and the formula Q-COOH can be used in dicyclohexylcarbodiimide or ruthenium-62- 200918053 3-Trimethylamine in the presence of a condensing agent such as 3-methylaminopropyl)-3-ethylcarbodiimide hydrochloride or hydrazine-p-benzotriazole The compound of the present invention (7-h) can be produced by carrying out the reaction in the presence or absence of diisopropylethylamine or the like. Further, by using the compound represented by the formula Q-COC1 in triethyl The compound (7-h) of the present invention can be produced by carrying out the reaction in the presence or absence of an amine, diisopropylethylamine or the like. Step (7 -1 2 ): In the solvent, the compound can be obtained by 7-h), the compound (7-j) of the present invention is produced by hydrolysis using a base such as an aqueous sodium hydroxide solution. Step (7-13). In the glutinous agent, the compound of the present invention (7-j) can be obtained. 'The compound of the present invention (7-1) is produced by using a sodium hydroxide aqueous solution or the like to form a sodium salt. Step (7-14): In the solvent, by using the compound (7-d), in the formula (3 1 ) [ In the presence of a compound represented by A0 (31) and a base such as potassium acetate, the reaction is carried out using a reagent such as ginseng (di-p-acetone) dipalladium (rhodium) or tricyclohexylphosphine. The compound (7-rn) is produced. Step (7 -1 5 ): in the solvent, the compound (7 _ m ) can be used in the presence of a base such as sodium carbonate, ruthenium triphenylphosphine palladium In the presence of a palladium reagent, and formula (32) -63- 200918053 [40]

The compound represented is subjected to a reaction to produce a compound (7-n). Step (7-16): In the solvent, the compound (7-n) can be deprotected by reacting under acidic conditions such as hydrochloric acid to produce a compound (7-f). Step (7-17): Solvent In the presence of a compound (7-d) in the presence of a base such as sodium carbonate or a palladium reagent such as ruthenium triphenylphosphine palladium, and the formula (3 3 )

Or (34) 42]

The compound represented by OH ΒΌΗ R2b is reacted to produce a compound (7-n). Step (7 - 18): in the solvent, by using the compound (7-m) in the presence of a base such as sodium carbonate, palladium triphenylphosphine palladium or the like in the presence of a palladium reagent, and formula (35) 〔化43〕

The compound shown is subjected to a reaction to produce a compound (7-e). -64- 200918053 Scheme 8: Method for producing compound (8-g) of the present invention from compound (7-a) [Chem. 44]

(In the flow chart, Q, R2a, R2b, and Y have the same meaning as described above, and G and J represent pixel atoms). Step (8-1): In the solvent, a compound represented by the compound (7-a) and the compound of the formula (3 6 ) (formation 45) can be reacted in the presence of a base such as sodium hydride to produce a compound. (8-b) = Step (8-2): in the presence of a palladium reagent such as triphenylphosphine palladium or the like in the presence of a compound (8-b), a base such as sodium carbonate, or the like , make the formula (3 7 ) -65- 200918053 [Chem. 46] R' ?H^CB, 〇o2N^R2b

*OH (37) or formula (38) [chemical 4 7]

2b (38) 〇>: The compound represented is reacted to produce a compound (8-c). Step (8-3): in the solvent, the compound (8-c) can be reacted under a hydrogen atmosphere, a 10% palladium carbon, a 2% molybdenum carbon or the like to produce a compound (8). - d ). Further, in the solvent, the compound (8-d) can be produced by reacting the compound (8-c) in the presence of iron powder and ammonium chloride water. Step (8-4): in the solvent, a compound can be produced by reacting the compound (8-d) with a compound represented by the formula Q-NCO in the presence or absence of a base such as triethylamine. (8-e). Further, in the solvent, the compound (8-d) can be reacted with 4-nitrophenyl chloroformate in the presence of a base such as pyridine, and then reacted with a compound represented by the formula q-nh2. And the compound (8-e) was produced. Step (8-5): In the solvent, the compound (8-f) can be produced by reacting the compound (8-e) in the presence of an acid such as P-toluenesulfonic acid to prepare the compound (8-f): Step (8-6): In the solvent, the compound of the present invention can be produced by reacting the compound (8-f) with an acidifying agent such as m-chloroperbenzoic acid, etc. -66 - 200918053

Scheme 9: Process for producing the compound (9-h) of the present invention and the compound (9-i) of the present invention from the compound (7-b) [Chem. 48]

(In the scheme, Q, R2a, R2b, and Y have the same meanings as described above, and G and J represent halogen atoms). Step (9-1): in the solvent, a compound represented by the formula HO-Y-COOCH2Ph can be reacted in the presence of a compound (7-b), a base such as cesium carbonate or potassium carbonate, to produce a compound. (9-c). Step (9-2): In the solvent, the compound (9-d) can be produced by reacting the compound (9-c) in the presence of a metal reagent such as indium or molybdenum hexacarbonyl. Step (9-3): In the solvent, the formula (3 9) can be obtained in the presence of a base (9-d), a base such as sodium carbonate, and a palladium reagent such as ruthenium triphenylphosphine palladium. ) -67- 200918053 〔化49〕

(39) or formula (40) [chemical 5 0]

The compound is reacted to produce a compound (9 - e step (9-4): in a solvent] which can be produced by reacting a compound iron powder with ammonium chloride water or hydrochloric acid to prepare 9-f). Step (9-5): in the presence of a base such as a pyridine compound, a 4-nitrophenyl chloroformate is reacted with a compound represented by the formula Q-NH2 to produce g) . Further, in the solvent, the compound (9-g) can be produced by reacting with a compound of the formula Q-NCO in the presence or absence of a base such as a compound (9-f)amine. Step (9-6): In the solvent, the compound (9-h) can be produced by subjecting the compound to hydrolysis with a base such as an aqueous sodium hydroxide solution. Step (9-7): In the solvent, the present invention can be used. 1) 'The sodium salt is formed using an aqueous sodium hydroxide solution or the like to produce (9-i). The above schemes 1, 2, 3, 5, 6' 7, 8, and 9 (9-e), in the compound ((9-f), in the reaction, the compound (9 - in the triethyl group) Indicative compound: 9-g), the compound of the invention:: (9-h in the synthesis of the present invention, by -68-200918053 formula (14), formula (16), formula (20), formula (23 The reagents of the formula (25), the formula (27), the formula (37), and the formula (39) are changed to the formula (41) [Chemical 5 1]

The reagents represented by the formulae (15), (17), (21), (24), (26), (28), (38), and (40) , changed to formula (42) [52]

The compound described in (II) and (III) can be synthesized from the reagents shown. Examples of the salt group in the description of the general production method of the compound of the present invention include sodium carbonate, potassium carbonate, carbonic acid planer, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium hydroxide, sodium hydride, lithium hydride, sodium decylamine, and t. - an alkali metal salt such as potassium butoxide, η-butyl lithium or lithium diisopropyl decylamine, an amine such as triethylamine, diisopropylethylamine, pyrrolidine or piperidine, or acetic acid Sodium or potassium acetate oxime The acidifying agent in the description of the general production method of the compound of the present invention may, for example, be m-chloroperbenzoic acid, magnesium monoperphthalate 6 hydrate, peracetic acid or performic acid. Inorganic and organic peroxides, sodium periodate, etc., such as organic peracid, hydrogen peroxide, urea hydrogen peroxide, phthalic anhydride, t-butyl hydroperoxide or cumene hydroperoxide, 〇XOne (registered trademark), N-bromosuccinimide, N-chlorosuccinimide, chloramine-T, -69- 200918053 t-butyl hypochlorite, iodobenzene diacetate or bromine-1 , 4-Diazabicyclo[2,2,2]octane addition complex. The reducing agent in the description of the general production method of the compound of the present invention may, for example, be sodium borohydride or lithium borohydride. The meaning of the solvent in the description of the general production method of the compound of the present invention is not particularly limited as long as it is stable under the reaction conditions and does not interfere with the reaction due to inactivity, and is not particularly limited. An alcohol such as water, methanol, ethanol, i-propanol, η-butanol or t-butanol, an ether such as dioxane or tetrahydrofuran, dimethylformamide, dimethylacetamide, or the like Methyl hydrazine, pyridine, ethyl acetate, dichloromethane, chloroform, acetone, acetic acid, benzene or toluene or a mixed solvent of these. The reaction temperature in the general production method of the compound of the present invention can be selected from the range of -78 ° C to the boiling point of the solvent used in the reaction. The production method can be under normal pressure, under pressure, and under microwave irradiation. Next Embodiment [Embodiment] [Examples] Hereinafter, in order to show the compounds of the present invention in more detail, reference examples, examples, and test examples are listed, but are not limited to the examples listed. (Reference Synthesis Example 1-1) -Production of (Esterylmethyl)cyclobutanecarboxylic acid ethyl ester -70-200918053 [Chem. 5 3]

(1) In a solution of cyclobutane-1,1-dicarboxylic acid diethyl ester (53.lg, 0.265 mol) in ethanol (300 ml), 1 M aqueous sodium hydroxide solution (2 6 5 ml) was added at room temperature. The mixture was stirred at room temperature for 24 hours. The reaction mixture was concentrated under reduced pressure. The residue was washed twice with hexane (100 ml). The aqueous layer was neutralized with 1M hydrochloric acid (210 ml) and chloroform (100 ml) After three times of extraction, the organic layer was washed with saturated brine, and the organic layer was dried over anhydrous magnesium sulfate. Ethoxycarbonyl)cyclobutanecarboxylic acid (37.2 g). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.31 ( t, J = 6.8 Hz, 3H ) 1.95-2.18 ( m, 2H ) 2.50-2.72 ( m5 4H ) 4.26 ( q, 2 = 1.2 Hz, 2H ) (2 a solution of 1-(ethoxycarbonyl)cyclobutanecarboxylic acid (31.0 g, 0-18 mol) in tetrahydrofuran (300 ml), borane, tetrahydrofuran complex tetrahydrofuran (200 ml) After stirring at room temperature for 20 minutes, it was quenched with methanol (25 ml), and the reaction mixture was concentrated under reduced pressure. The obtained residue was diluted with ethanol, and then concentrated under reduced pressure to give a crude product. Hydroxymethyl) cyclobutanecarboxylic acid. The obtained crude 1-(hydroxymethyl)cyclobutanecarboxylic acid was dissolved in ethanol (310 ml), concentrated hydrochloric acid (30 ml) was added at room temperature, and the mixture was stirred under reflux with heating for 3 hr. The reaction mixture was concentrated under reduced pressure, and the obtained residue was neutralized with saturated aqueous sodium bicarbonate - 71 - 200918053. The aqueous layer was extracted with chloroform and the organic layer was washed with saturated brine. The layer was allowed to stand, and the residue was filtered, and the solid was filtered. The filtrate was concentrated under reduced pressure to afford ethyl 1-(hydroxymethyl)cyclobutanecarboxylate (22.0 g). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.32 ( t, J = 6.8 Hz, 3H) 1.92-2.0 8 ( m, 4H) 2.36 ( t, J = 6.8 Hz, 1H) 2.38-2.50 ( m, 2H) 3.84 ( d, J = 6.6 Hz, 2H) 4.22 ( q, J = 7.2 Hz, 2H ) (Refer to Synthesis Example 1-2) Production of methyl 1-(hydroxymethyl)cyclobutanecarboxylate 〕

Synthetic Example 1-1) according to the method for producing ethyl 1-(hydroxymethyl)cyclobutanecarboxylate, using hydrogen chloride-methanol solution, liquid < 5-10%) and methanol in (2) Substituting concentrated hydrochloric acid and ethanol to give 1-(hydroxymethyl)cyclobutanecarboxylic acid methyl ester (colorless oil). 1 NMR (3 0 0 Μ H z, CD C1 3 ) 6 ppm 1 · 9 2 - 2 · 1 〇( m,4 Ή )2.33 ( t, 3 = 6.6 Hz, 1H ) 2.3 9-2.5 3 ( m, 2H ) 3.76 ( s 5 ό |^[ ) 3.85 ( d, J = 6.6 Hz , 2H ) (Reference Synthesis Example 1-3) Production of methyl 1-(hydroxymethyl)cyclopropanecarboxylate-72- 200918053 [Chemical 5 5] hoJ^o, Ο Based on 1-(hydroxymethyl) ring Process for producing ethyl butanecarboxylate (refer to Synthesis Example 1-1) by substituting cyclobutane-1,1-dicarboxylic acid diethyl ester for cyclobutane-1,1-dicarboxylic acid diethyl The base ester was prepared by substituting a hydrogen chloride-methanol solution (5-1 0%) and methanol with concentrated hydrochloric acid and ethanol in (2) to produce methyl 1-(hydroxymethyl)cyclopropanecarboxylate (colorless oil). 1H NMR (3 00 MHz, CDC13) δ ppm 0.83 -1 .〇〇( m, 2H )1.23 - 1.3 9 ( m, 2H) 2.4 8 -2.60 ( m, 1H) 3.63 ( d, J= 6.8 Hz, 2H) 3.70 ( s, 3H ) (Reference Synthesis Example 1-4) Preparation of ethyl 1-(hydroxymethyl)cyclopropanecarboxylate] [Chemical 5 6] 〇 Based on 1-(hydroxymethyl) A method for producing ethyl cyclobutanecarboxylate (refer to Synthesis Example 1-1), which is substituted by cyclopropyl-1,1-dicarboxylic acid diethyl ester to cyclodane-1,1-dicarboxylic acid Ethyl ester 'Manufacture of ethyl 1-(transmethyl)cyclopropanecarboxylate (colorless oil). 1 NMR (3 00 MHz, CDC13) δ ppm 0.89 ( dd, J-4.2 Hz, 6.8 Hz, 2H) 1.20- 1.3 6 ( m, 5H) 2.59 ( t, J = 6.8 Hz, 1H) 3.64 ( d, J = 6_8 Hz, 2H) 4.17 ( q, J = 7"Hz, 2H) (Refer to Synthesis Example 1 - 5 ) -73- 200918053 Manufacture of ethyl i-(hydroxymethyl)cyclopropanecarboxylate 2 Manufacture of 1-(hydroxymethyl) according to the method of Tetrahedron Letters, 40 (30) '5467-5470 (1999) Cyclopropylidene carboxylate (colorless oil). (Reference Synthesis Example 1-6) Production of methyl 1-(hydroxymethyl)cyclopentanecarboxylate [Chem. 5 7]

According to the production method of ethyl 1-(hydroxymethyl)cyclobutanecarboxylate (refer to Synthesis Example 1-1), cyclobutane-1 was replaced by using cyclopentane-Id-dicarboxylic acid dimethyl ester. , 1-dicarboxylic acid diethyl ester, in (2) using hydrogen chloride-methanol solution (5 - 10%) and methanol to replace concentrated hydrochloric acid and ethanol to produce 1-(hydroxymethyl)cyclopentanecarboxylic acid A Base ester (colorless oil). 1H NMR ( 3 00 MHz, DMS0-d6) δ ppm 1.43 - 1.70 ( ra, 6H ) 1.80- 1.97 ( m, 2H ) 3.46 ( d, J = 5_7 Hz, 2H ) 3.60 (s, 3H ) 4.85 ( t, J = 5.5 Hz, 1H ) (Reference Synthesis Example 1 - 7) Production of ethyl hydroxymethyl)cyclohexanecarboxylate [Chem. 5 8]

According to ethyl 1-(hydroxymethyl)cyclopropanecarboxylate (Ref. -74 - 200918053

Tetrahedron Letters, 40 (30), 5467-5470 (1 999)), by replacing cyclopropane-1,1-dicarboxylic acid with diethyl hexane-l,l-dicarboxylate Ethyl ester to produce ethyl 1-(hydroxymethyl)cyclohexanecarboxylate (colorless oil). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.17-1.61 ( m, 11H) 1.90-2.09 ( m, 3H) 3.63 ( d, J = 6.5 Hz, 2H ) 4.09-4.25 ( m,2H ) (Reference Synthesis Example) 1-8) Manufacture of benzyl 1-(hydroxymethyl)cyclopropanecarboxylate [Chem. 5 9]

-75- 200918053 651: The following side was added dropwise 1 M diisobutylaluminum hydride toluene solution ( 29.3 ml, 20.0 mmol). The temperature of the reaction solution was raised to -15 C. The temperature was in this state. A saturated aqueous solution of chlorinated solution (40 ml) was added to the reaction mixture, followed by the addition of 1 M hydrochloric acid (40 ml). The reaction mixture was filtered over a mixture of sulphite and washed with chloroform to separate the aqueous layer. The organic layer was washed with saturated brine. Drying with anhydrous magnesium sulfate, passing the filtrate and concentrating the filtrate. The obtained residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 4:1) to give an oily product. Methyl)cyclopropanecarboxylic acid benzyl ester (1.33 g). 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 0.88-0.92 ( m, 2H ) 1.31-1.34 ( m, 2H ) 2.53 ( t, J = 6.9 Hz, 1H ) 3.65 ( d, J = 6.9 Hz, 2H) 5.14 ( s, 2H ) 7.3 0-7.40 ( m, 5H ) (Reference Synthesis Example 1-9) Production of benzyl 1-(hydroxymethyl)cyclobutanecarboxylate [Chem. 60]

HO Ο According to the method of producing benzyl-(hydroxymethyl)cyclopropanecarboxylic acid benzyl (refer to Synthesis Example I-8), by using I,3-diiodopropane instead of hydrazine, 2-dibromoethane 1-(Hydroxymethyl)cyclobutanecarboxylic acid benzyl _. 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.9ι.2.〇8 ( m, 4H )2.26 ( t, J = 6.7 Hz, 1H) 2·4〇-2.55 ( m,2h) 3 8 5 ( d , J = 7 Hz, 2H) 5.18 ( s, 2H) 7.31-7.45 (m -76- 200918053 (Refer to Synthesis Example 1-1) Manufacture of 1-(hydroxymethyl)cyclopentanecarboxylic acid benzyl ester [ 6 1] According to the production method of benzyl 1-(hydroxymethyl)cyclopropanecarboxylate (refer to Synthesis Example 1-8) 'Replacement of hydrazine by using 1,4-diiodobutane, 2-dibromoethane Alkyl to give benzyl 1-(hydroxymethyl)cyclopentanecarboxylate. 1H NMR (3 00 MHz, CDC13) δ ppm 1.57- 1.80 (m, 6H) 1.92-2.09 (m, 2H) 2.53 (t, J = 6.8 Hz, iH) 3.59 ( d, J = 6.8 Hz, 2H) 5.15 ( s, 2H) 7.26-7.41 ( m, 5H) (Refer to Synthesis Example 2-1) 1- {[( 5-Bromopyridine- Manufacture of 2-ethyl)oxyjmethylmethylcyclobutanecarboxylate ethyl ester

Square < 5-ί臭-2-气啦|]定(16.33g, 92.79mmol) in a solution of xylene (120ml), adding carbonic acid planing at room temperature (6〇5g, 185 58mm〇1), A solution of ethyl hydroxymethyl)cyclobutanecarboxylate (21-98 g, l 3 8.95 mmol) in xylene (43 ml) at room temperature! On the day, the mixture was stirred under reflux for 8 hours. After the reaction was completed, the reaction solution was subjected to filtration of fluorite. The reaction mixture was concentrated under reduced pressure. The obtained residue was chromatographed on a silica gel column (developing solvent; ethyl acetate: Purification of the alkane=1: i 〇] afforded 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylate ethyl ester as a pale yellow-77-200918053 color oil (15.7 g). MS ( ESI ) : 3 14, 3 1 6 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.23 ( t, J = 7.1 Hz, 3H ) 1.90-2.15 ( m, 4H) 2.43 -2.5 6 ( m, 2H) 4.17 ( q, J = 7.2 Hz, 2H ) 4.54 ( s, 2H ) 6.65 ( dd, J = 0.6 Hz, 9.0 Hz, 1H ) 7.63 ( dd, J = 2.4 Hz, 8.7 Hz, 1H ) 8.18 ( d, J = 2.4 Hz, 1H ) (Reference Synthesis Example 2-2 ) Production of methyl 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylate 63]

(1) In a solution of 5-bromo-2-fluoropyridine (13.42g, 76.25mmol) in xylene (90ml), add carbonic acid (49.16g, 1 5 0.8 8mmol), 1- (hydroxymethyl) at room temperature After a solution of ethyl cyclobutanecarboxylate (18-05 g, 114.09 mmol) in xylene (40 ml), the mixture was stirred under reflux with heating for 1 6.5 hours. After the reaction was completed, the reaction mixture was filtered through a solution of Concentration under reduced pressure gave ethyl 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylate (26.8 g). C 2 ) Tetrahydrofuran (180 ml) and methanol (-78-200918053 90 ml) in ethyl 1-{[(5-bromopyridin-2-yl)oxy]methylindolecyclobutanecarboxylate (26.8 0g) In the mixed solution, 6 M sodium hydroxide water (6 ml) was added at room temperature, and the mixture was stirred at room temperature for 1 day. After the reaction was completed, concentrated hydrochloric acid was added to the reaction mixture to make pH 2, and ethyl acetate (20 ml) was used. The organic layer was washed with water (200 ml, twice), and the aqueous layer was extracted with brine (2 ml). The filtrate was concentrated under reduced pressure to give crude-1-{[(pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid as a brown color. The obtained crude ethyl acetate/hexane was recrystallized to give 1 -{bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid (16.8 8 g) as a pale brown solid. (3) After adding acid (10 ml) to a solution of 1-{[[5-bromopyridin-2-yl)oxy]methyl}carboxylic acid (16.S7g) in methanol (170 ml) After stirring for 5 hours, after completion of the reaction, the solution was neutralized with 6 M aqueous sodium hydroxide solution under ice-cooling, and then ethyl acetate (100 ml) was diluted, and the mixture was washed with water (100 ml, and the aqueous layer was treated with acetic acid). Ethyl acetate (2 00 ml '2 times) was extracted, and the organic layer was washed with saturated brine (1 〇〇ml), dried over magnesium sulfate, filtered and evaporated. Purification by hydrazine column chromatography (developing solvent; ethyl acetate: hexanes) to afford 1-{[( 5-bromopyridin-2-ylmethyl)cyclobutanecarboxylic acid methyl ester (15.16 g MS ( ESI ) : 3 00,3 02 ( M+l ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.90-2.20 ( ) 2.40-2.60 (m, 2H) 3.71 (s, 3H) 4.53 (s , 2H) solution (diluted ethyl ester in cold ice (washing and drying out 5-bromopyrene by B [(5-cyclobutane into concentrated salt to use the reaction solution with B 2 times) =1 : base) oxygen m, 4H 6.65 ( -79- 2 00918053 d, J = 8.9Hz, 1H ) 7.63 ( dd, J = 2.8Hz, 8.8 Hz, 1H ) 8.17 ( d, J = 2.4Hz, 1 H ) (Refer to Synthesis Example 2-3) 1- {[ ( 5 -Bromopyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid ethyl vinegar ([64]

By the method for producing 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanyl residue ethyl ester (refer to Synthesis Example 2-1), by using 1_(radiomethyl) Substituting ethyl cyclopropanecarboxylate for 1-(hydroxymethyl)cyclobutanyl ethyl phthalate to produce ethyl 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclopropanecarboxylate Ester (colorless oil). MS ( ESI ) : 3 00, 3 02 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.01 ( q, J = 3.7 Hz, 2H ) 1.2 1 ( t, J = 7.1 Hz, 3H ) 1.36 ( q, J = 3 .8 Hz, 2H ) 4.15 ( q,3 = 7.1 Hz, 2H ) 4.42 ( s, 2H ) 6.67 ( d, J = 8.4Hz, 1H ) 7-63 ( dd, J = 2.6Hz, 8.6 Hz, 1H ) 8.16 ( d, J = 2.4 Hz, 1H ) (Refer to Synthesis Example 2-4) b {(( 5-Bromopyridin-2-yl)oxy)methyl}cyclopropanecarboxylic acid methyl ester Manufacturing (chemical 6 5)

200918053 According to the production method of 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid ethyl ester (refer to Synthesis Example 2-1), by using 1-(hydroxymethyl group) Substituting methyl cyclopropylpropanate for ethyl 1-(hydroxymethyl)cyclobutanecarboxylate to produce 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid Base ester (colorless solid). MS ( ESI ) : 286,28 8 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.02 (q, J-3.8Hz, 2H ) 1.37 ( q, J = 3.7 Hz, 2H ) 3.70 ( s , 3H ) 4.42 ( s, 2H ) 6.68 ( d, J = 9.0 Hz, 1H ) 7.64 ( dd, J 2.6 Hz, 8.9 Hz, 1H ) 8.15 ( d, J = 2.4 Hz, 1 H ) (Reference Synthesis Example) 2 - 5 ) Production of 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclopentanecarboxylic acid methyl ester [Chem. 66]

By the method for producing 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutylene carboxylate (refer to Synthesis Example 2-1) by using 1-(hydroxymethyl) Substituting methyl cyclopentanecarboxylate for 1-(hydroxymethyl)cyclobutyl carboxylic acid ethyl vinegar to produce 1-{[(5-indolyl-2-yl)oxy]methyl}cyclopentane carboxylate Acid methyl ester (thin yellow solid).

1H NMR (300 MHz, CDC13) 5 ppm 1.5 0-1.8 0 ( m, 6H ) 2.07-2.20 ( m, 2H ) 3.69 ( s, 3H ) 4.34 ( s, 2H ) 6.65 ( d, J = 8.7 Hz , 1H) 7.63 ( dd, J = 2.7 Hz, 8.7 Hz, 1H) 8.17 ( d, -81 - 200918053 J = 2, 4 Hz, 1 H ) (Refer to Synthesis Example 2-6) 1- {[( 5-bromo) Manufacture of ethyl pyridin-2-yl)oxy]methyl}cyclohexanecarboxylate [Chem. 67]

According to the production method of 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid ethyl ester (refer to Synthesis Example 2-1), by using 1-(hydroxymethyl) Substituting ethyl 1-cyclo(hydroxymethyl)cyclobutanecarboxylate to prepare 1-{[[5-bromopyridin-2-yl)oxy]methyl}cyclohexanecarboxylic acid Ethyl ester (colorless oil). 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.20 ( t, J = 7. 1 Hz, 3H) 1.24-1.66 (m, 8H) 2.06-2.18 (m, 2H) 4.08-4.19 (m,2H) 4.3 0 ( s, 2H ) 6.63 ( dd, J = 0.6 Hz, 8.7 Hz, 1 H ) 7.62 ( dd, J = 2.7 Hz, 8.7 Hz, 1H) 8.16 ( d, J = 2.4 Hz, 1H ) (Refer to Synthesis Example 2 -7) Preparation of 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylic acid methyl ester [Chem. 6 8]

According to the method for producing 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxy-82-200918053 acid ethyl ester (refer to Synthesis Example 2-1), by using toluene instead of Toluene, 5-bromo-2-chloropyrimidine was substituted for 5-bromo-2-fluoroin, and 1-(hydroxymethyl)cyclobutanecarboxylic acid methyl ester was substituted for 1-(hydroxymethyl)cyclobutanecarboxylate. Acid ethyl ester to produce methyl hydrazine-([5-bromopyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylate (colorless solid). 1Η NMR ( 3 00 MHz, CDC13) § ppm 1.95 -2.22 ( m, 4H )2.4 6 - 2.5 9 ( m,2 Η ) 3 7 2 ( s,3 Η ) 4.6 0 ( s,2 Η ) 8 · 5 2 ( s, 2H ) (Reference Synthesis Example 2-8) Preparation of 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylic acid ethyl ester [Chem. 69]

By the method for producing 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 2-7), by using a 1-(hydroxymethyl) ring Preparation of 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylate Ethyl Ester by replacing the methyl 1-(hydroxymethyl)cyclobutanecarboxylate with ethyl propanecarboxylate . MS (ESI): 301, 303 ( Μ + 1) 1 NMR ( 300 MHz, CDC13) δ ppm 1.06 (dd, J = 4.3 Hz, 7.0 Hz, 2H) 1.21 (t, J = 7.〇Hz, 3H) 1.41 (dd, J = 4.6 Hz, 7.3 Hz, 2H) 4.14 ( q, J = 7.1 Hz, 2H) 4.51 ( s, 2H) 8.5 3 ( s, 2H ) -83- 200918053 (Refer to Synthesis Example 2-9) Manufacture of 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylic acid methyl ester

[Chemical formula 7] According to the method for producing methyl 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylate (refer to Synthesis Example 2_7) 'by using Substituting a methyl ester of cyclopropanecarboxylate for methyl 1-(hydroxymethyl)cyclobutanecarboxylate to produce 1-{[(5-bromopyrimidin-2-yl)oxy]methylindole cyclopropanecarboxylic acid Methyl ester (colorless solid) ° MS ( ESI ) · 287, 289 ( M + l ) 1H NMR ( 300 MHz, CDC13) δ ppm 1.06 ( q, J = 3.9 Hz, 2H ) 1.40 ( q, J = 3.9 Hz , 2H ) 3.69 ( s, 3H) 4.49 ( s, 2H ) 8.52 ( s, 2H ) (Reference Synthesis Example 2-10) 1- {[( 5-Bromopyrimidin-2-yl)oxy]methyl}cyclopentyl Manufacture of alkyl carboxylic acid methyl esters [Chem. 7 1]

According to the method for producing methyl {[(5-bromopyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 2-7), by using 1-(hydroxy-84-200918053) Substituting methyl (meth)methylcyclopentanecarboxylate for methyl 1-( hydroxymethyl)cyclobutanecarboxylate to produce 1-{ [( 5-bromopyrimidin-2-yl)oxy]methyl} ring Methyl pentanecarboxylate (colorless solid). MS ( ESI ) : 3 1 5,3 1 7 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.5 5 - 1.8 5 ( m, 6H ) 2.07-2.24 ( m, 2H) 3.69 ( s, 3H) 4.43 ( s, 2H ) , 8.52 ( s, 2H ) (Reference Synthesis Example 3 - 1 ) 1- ( { 〔 5_ ( 4_Aminophenyl)pyridin-2-yl)oxy}methyl)cyclobutane Manufacture of alkyl carboxylic acid methyl esters (72)

In a solution of 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid methyl ester (1.84 g, 6.12 mmol) in 1,4 - 2 chew (36 ml), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.41g, 6.4 2mmol), triphenyl was added under nitrogen atmosphere Base phosphine (〇.481g, l_84mmol), palladium acetate (Π) (0.137g, 0.612mmol) 'Add 2Μ aqueous sodium carbonate solution (15.3ml) 'stirred at 80 ° C for 1 hour' and let the reaction solution cool to room temperature After that, it was diluted with ethyl acetate and water, and the aqueous layer was separated, and the organic layer was washed with saturated brine, and then dried over anhydrous magnesium sulfate and silica gel, and the solid was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-85-200918053 ester:hexane = 1: 4 to 1: 2, and NH phthalate, ethyl acetate:hexane = 1:3). The product was diluted with ethyl acetate, washed with warm water (5 5 ° C) and brine, and dried over anhydrous magnesium sulfate. ( { 〔 5- (4-Aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (1.64 g). MS ( ESI ) : 3 1 3 ( M+l )

1 H NMR ( 3 00 MHz, CDC13 ) δ ppm 1 .90-2.20 ( m, 4H) 2.45-2.60 ( m, 2H ) 3.72 ( s, 3H) 3.6 5 - 3.8 5 ( br, 2H ) 4.59 ( s, 2H ) 6.75 ( d, J = 8.3 Hz, 2H ) 6.77 ( d, J = 8.6

Hz, 1H ) 7.32 ( d, J = 8.3 Hz, 2H ) 7.71 ( dd, J = 2.7Hz, 8.6

Hz, 1 H ) 8.29 ( d, J = 2.7 Hz, 1 H ) (Reference Synthesis Example 3 - 2 ) 1-( {[ 5-(4-Aminophenyl)pyridin-2-yl]oxy}methyl Manufacture of methyl cyclopropanecarboxylate [Chem. 73]

According to the method for producing methyl 1-( { [ 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate (refer to Synthesis Example 3-1) 'by use 1-{[(5-Bromopyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid methyl ester substituted 1-{[(5-bromopyridin-2-yl)oxy]methylindole Cyclobutanecarboxylate Acid methyl ester to produce 1-({[5-(4-aminophenyl)pyridin-2-yl)oxy-86-200918053}methyl)cyclopropanecarboxylic acid methyl ester (colorless solid). MS ( ESI ) : 299 ( M+l ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.06 (q, J = 3.8 Hz, 2H) 1.38 ( q, J = 3.4 Hz, 2H) 3.72 ( s, 3H) 3.72-3.85 (br, 2H ) 4.48 ( s, 2H) 6.76 ( d, J = 8.4 Hz, 2H ) 6.80 ( d, J = 9.0 Hz, 1H ) 7.32 ( d, J = 8. 1 Hz, 2H ) 7.73 ( dd, J = 2.7 Hz, 8.7 Hz, 1H) 8.27 ( d, J = 2.4 Hz, 1H) (Refer to Synthesis Example 3 - 3 ) Bu ({[ 5-(4-Aminophenyl)pyridine-2-) Manufacture of ethyloxy]methyl)cyclopropanecarboxylic acid ethyl ester

According to the method for producing 1-(丨[5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-1), by using 1-{[(5-Bromopyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid ethyl ester substituted 1 - {[(5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylate Acid methyl ester to produce ethyl 1-({[5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylate (yellow solid). 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.04 ( dd, J = 4.1 Hz, 7.1 Hz, 2H) 1.22 ( t, J = 6.9 Hz, 3H) 1.3 2- 1.40 ( m, 2H ) 3.65-3.82 (br , 2H) 4.16 (q, J = 7.1 Hz, 2H) 4.49 (s, 2H) 6.72-6.82 ( m, 3 H) 7.2 8-7.3 6 ( m, 2 H) 7.72 ( dd, -87- 200918053 J = 2.4 Hz, 8.4 Hz, 1 H) 8.28 ( d, J-1.8 Hz, 1H) (Refer to Synthesis Example 3-4) 1-( { 〔5- (4-Alkyl basic) U is 卩--2-yl Manufacture of methyl}methyl carboxylic acid methyl ester [Chemical Formula 75] According to the method for producing methyl 1-({[ 5-(4-aminophenyl)pyridin-2-yl])cyclobutanecarboxylate ( Reference Synthesis Example 3 - 1 Substituting 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclopentyl ester for 1-{[(5-bromopyridin-2-yl)oxy]methyl} Acid methyl ester to produce 1-({[4-(4-aminophenyl)pyridin-)methyl)cyclopentanecarboxylic acid methyl ester (light oil). MS (ESI): 3 27 ( M+ 1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.65-6H) 2.10-2.23 ( m, 2H) 3.67- 3.80 ( br, 2H) 3.7 ) 4.41 ( s, 2H) 6.73 -6.80 ( m , 3H) 7.2 9-7.3 6 ( 7.72 ( dd, J = 2.4 Hz, 8.6 Hz, 1 H ) 8.29 ( dd, J = 0. Hz, 1 H ) (reference Example 3 - 5 ) 1-( { 〔5-(4-Alkyl basic) fluorene-pyridin-2-yl)oxy}methyl carboxylic acid ethyl ester) Cyclopentane

Oxygen}methyl), by alkanecarboxylic acid, cyclobutane, carboxy-2-yloxyl, 1.85 (m, 1 (s, 3 Η m, 2H) 7 Hz, 2.5) cyclohexane-88- 200918053 [ 76]

According to the method for producing 1-({[5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-1), by using 1-{[(5-Bromopyridin-2-yl)oxy]methyl}cyclobutane substituted by ethyl 1-{[(5-bromopyridin-2-yl)oxy]methyl}cyclohexanecarboxylate Methyl carboxylic acid ester to give ethyl 1-({[4-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclohexanecarboxylate (colorless amorphous crystal). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.2 1 ( t, J = 7. 1 Hz, 3H) 1.40-1.69 (m, 8H) 2.10-2.21 (m, 2H) 3.74 (s, 2H ) 4.16 ( q , J = 7. 1 Hz, 2H ) 4.36 ( s, 2H ) 6.72-6.7 8 ( m, 3H ) 7.2 7 -7.3 5 ( m, 2H) 7.70 ( dd, J = 2.4 Hz, 8.7 Hz, 1H) 8.28 ( d, J = 2.4 Hz, 1H ) (Reference Synthesis Example 3 - 6 ) 1-( {[ 5-(4-Aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid ethyl Production of esters (Chem. 7 7)

A method for producing methyl ({[4-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate (refer to Synthesis Example 3-1) by using 1 - {[(5-Bromopyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylic acid B-89- 200918053 base ester substituted 1-{[(5-bromopyridin-2-yl)oxy]methyl} ring Methyl butanecarboxylate to give ethyl 1-({[5-(4-aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylate (colorless solid). 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.08 ( dd, J-4.2 Hz, 7.2 Hz, 2H) 1.21 ( t, J = 7.1 Hz, 3H) 1.39 ( dd, J = 4_2 Hz, 7.2 Hz, 2H) 3.73 -3.87 ( br, 2H ) 4.15 ( q, J = 7.2 Hz, 2H) 4.56 ( s, 2H) 6.7 5 -6.82 ( m, 2H) 7.29-7.3 5 ( m, 2H ) 8.64 ( s, 2H ) ( Reference Synthesis Example 3-7) Production of methyl 1-({[ 5-(4-aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylate [Chem. 7 8]

According to the method for producing methyl 1-( { [ 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate (refer to Synthesis Example 3-1), by using Substituting 1-{[[5-bromopyridin-2-yl)oxy]methyl}cyclobutanecarboxylate with methyl {[(5-bromopyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylate Acid methyl ester to produce 1-({[5-(4-aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (colorless solid). MS ( ESI ) : 3 1 4 ( M+ 1 )

1H NMR ( 3 00 MHz, CDC13) δ ppm 1.9 5 -2.3 0 ( m, 4H ) 2.47-2.63 ( m, 2H) 3.74 ( s, 3H) 3.74-3.90 ( br, 2H -90- 200918053 )4.67 ( s , 2H ) 6.79 ( d, J = 8.3 Hz, 2H ) 7.32 ( d, J = 8.3 Hz, 2H ) 8.64 ( s, 2H ) (Reference Synthesis Example 3 - 8 ) 1-( {[ 5-(4-amine) Manufacture of methyl phenyl)pyrimidin-2-yl]oxy}methyl)cyclopentanecarboxylic acid methyl ester

According to the method for producing 1- ({[ 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-1), by using 1-{[(5-Bromopyrimidin-2-yl)oxy]methyl}cyclopentanecarboxylic acid methyl ester substituted 1 - {[(5-bromopyridin-2-yl)oxy]methyl}cyclobutane Methyl carboxylic acid ester to give 1-({[5-(4-aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclopentanecarboxylic acid methyl ester (colorless solid). MS ( ESI ) : 3 2 8 ( M+l ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1 .6 5 - 1.8 8 ( m, 6H) 2.13-2.24 (m, 2H) 3.70 (s, 3H) 3.76-3.87 (br, 2H ) 4.48 ( s, 2H ) 6.78 ( d, J = 8.7 Hz, 2H) 7.31 ( d, J = 8.7 Hz, 2H ) 8.63 ( s, 2H ) (Refer to Synthesis Example 3-9) Manufacture of methyl 1-({[ 5-(4-amino-2-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate-91 - 200918053 [化80]

(1) Acetic anhydride (1.3 g, 12.73 mmol) and formic acid in a solution of 4-bromo-3-fluoroaniline (2 g, l.53 mmol) in tetrahydrofuran (10 ml) and toluene (10 ml) The mixed solution of 2.3 g and 49.97 mmol) was dripped for 15 minutes, the reaction liquid was warmed to room temperature, and the mixture was stirred for 4 hours, and the reaction liquid was diluted with ethyl acetate, and washed with a 1 N aqueous hydrochloric acid solution and a saturated aqueous sodium carbonate solution. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and the resulting solid was suspended in a mixture of diethyl ether and hexane, and the solid was filtered to give a colorless solid. Bromo-3-fluorophenyl)carhamamine (2.3 g). MS ( ESI ) : 220 ( M+1 ), 218 (M-1) 1H NMR (3 00 MHz, CDC13) δ ppm 6.76-6.92 ( m, 1 H ) 7.9-7.12 ( m, 1H) 7.46-7.64 ( m, 2H ) 8.40 ( d, J = 1.2 Hz, 1 H ) (2) 1-{[(5-Bromopyridin-2-yl)oxy]methyl}cyclobutane decanoic acid methyl vinegar (500 mg, a solution of 1.666 mmol), potassium acetate (245 mg, 2.4964 mmol), bis(pin ac ο 1 at e) diboron (4 6 5 mg, 1.83 26 mmol) in 1,4-dioxane (1 7 m 1 ), Under stirring in an argon atmosphere at 80 ° C, Pd2 ( dba ) 3 (55 mg, 0-060 mmol, dba: bis(dibenzylideneacetone)), tricyclohexylphosphine (100 mg, 0.3499 mmol) of 1, 4-Dioxane (l〇ml) solution was dropped, -92- 200918053, stirred at 80 ° C for 19 hours, allowed to cool to room temperature, filtered by fluorite to remove solids, concentrated filtrate, will The obtained residue was subjected to crude chromatography on silica gel column chromatography (eluent solvent; chloroform) to afford crude crude oil as a yellow oil (1[(5,4,5,5,5-tetramethyl-1,3, Methyl 2-dioxaoxol-2-yl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate (1.lg). In the crude 1-( { 〔 5-( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxy}methyl) Methyl cyclobutanecarboxylate (550 mg), N-(4-bromo-3-fluorophenyl)carbenamide (182 mg, 〇.8 3 48 mmol), palladium (II) acetate (19.0 mg, 0.0846) Methyl), triphenyl o- (67.0 mg, 0.2554 mmol) in a solution of 1,4 - dioxin (7 ml), 2 M sodium carbonate aqueous solution (2_0 ml, 4.00 mmol) was added at room temperature under a nitrogen atmosphere at 80 ° After stirring for 12 hours, the mixture was allowed to cool to room temperature, and then the mixture was diluted with ethyl acetate. The organic layer was washed with water, and the organic layer was concentrated, and the obtained residue was chromatographed on a silica gel column. Purification with ethyl acetate = 10: 1 to 1: 2 to give 1-[({ 5-[2-fluoro-4-(methylamino)phenyl)pyridin-2-yl as a red oil. }Oxy)methyl]cyclobutanecarboxylic acid methyl ester (190 mg). MS (ESI): 3 59 (M+l), 357 (Ml) 1H NMR (3 00 MHz, CDC13) δ ppm 1.98-2.17 ( m, 4H ) 2.52-2.5 8 ( m, 2H ) 3.73 ( s, 3H ) 4.62 ( s, 2H) 6.80-6.84 ( m, 1H) 7.22-7.39 ( m, 2H ) 7.60-7.63 ( m, 1H) 7.73 -7.76 ( m, 1H) 8.30 ( s, 1H) 8.42 ( s, 1H 8.72-8.76 (m, 1H) (3) in l-[({5-[2-oxo-4-(methylamino)phenyl]-93- 200918053 pyridin-2-yl}oxy) a solution of methyl 4-cyclobutanecarboxylate (67 mg, 0.18 69 mm 〇l) in methanol (1.5 ml) was added with concentrated hydrochloric acid (0.17 m1) under ice cooling, and stirred at the same temperature for one hour. The reaction mixture was neutralized with a saturated aqueous solution of sodium carbonate and diluted with chloroform. The organic layer was washed with saturated brine, and the organic layer was concentrated, and the obtained residue was chromatographed on a silica gel column [ NH oxime, developing solvent; hexane: Purification with ethyl acetate = 1 : 1] gave 1-({[5-(4-amino-2-fluorophenyl)pyridin-2-yl)oxy}methyl)cyclobutanecarboxylate as a red oil. Acid methyl ester (57 mg). MS ( ESI ) : 33 1 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1 · 4 0 - 1 . 8 0 ( br, 2 H ) 1.94-2.19 ( m, 4H) 2.49-2.5 8 ( m, 2H) 3.72 ( s, 3H) 4.60 ( s, 2H ) 6.4 5 -6.54 ( m, 2H) 6.77-6.80 ( m, 1H) 7-13-7.26 ( m, 1H) 7.69-7.73 (m, 1H) 8.26 ( s, 1H) (Reference Synthesis Example 3 -1 0 ) b (丨[5-(4-Amino-2-chlorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate Manufacture of acid methyl esters (chemical 8 1)

According to the production method of Reference Synthesis Example (3-9), 1-({[4-(4-amino-2-)-2-) was obtained by substituting 4-bromo-3-chloroaniline with 4-bromo-3-fluoroaniline. Chlorophenyl)pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester. (1) N-(4-bromo-3-chlorophenyl)carboxylic acid amine -94 - 200918053 [Chem. 8 2]

Brown solid MS (ESI): 23 6 (M+l), 23 4 (Ml) 1 H NMR (3 00 MHz, CDC13) δ ppm 7.2 1-7.32 ( m, 2H )7.54-7.61 ( m, 1H) 7.80 ( d, J = 2.7 Hz, 1H) 8.3 9-8.40 ( m, 1 H ) (2 ) 1 -[ ( { 5 -[ 2 -chloro-4-(methylmercapto)phenyl]pyridine-2 -yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester [Chemical 8 3]

Colorless oil MS (ESI): 3 7 5 (M+l), 3 73 (Ml) 1H NMR (3 00 MHz, CDC13) δ ppm 1.97-2.19 ( m, 4H ) 2.5 0-2.5 9 ( m, 2H) 3.73 ( s, 3H) 4.62 ( s, 2H) 6.79-6.83 ( m, 1H) 7.23 -7.3 3 ( m, 2H) 7.48-7.51 ( m, 1H) 7.66-7.69 ( m, 1H) 7.79 ( d , J = 2.1 Hz, 1H) 8.19 ( d, J = 2.4 Hz, 1 H ) 8.42 ( d, J = 1.5 Hz, 1 H ) (3) 1-( { 〔5- (4 -Amino- 2-Chlorobenzyl)methane-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester colorless oil MS (ESI): 34 7 (M+l)

1H NMR ( 3 00 MHz, CDC 1 3 ) δ p pm 1 · 9 4 - 2.1 9 ( m, 4 H -95- 200918053 ) 2.49-2.58 ( m, 2H ) 3.73 ( s, 3H) 3.75-3.85 ( br5 2H) 4.60 (s, 2H) 6.61-6.65 (m, 1H) 6.76-6.81 (m, 2H) 7.08 (d, J=8.4 Hz, 1H) 7.63 -7.6 7 ( m, 1H) 8.16 ( d, J = 2.4 Hz, 1 H ) (Reference Synthesis Example 3 -1 1 ) 1-( {[ 5-(4-Amino-2-methylphenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate Manufacture of acid methyl ester

Residual methyl ester (121.91 «§, 0.406111111〇1), 4,4,5,5-tetramethyl-2-(2-methyl-4-nitrophenyl)-1,3,2-di Hexoxyborane (1 17.6 mg, 〇.447 mmol, synthesized according to Tetrahedron, 62, 2583-2589 (2006)), acetic acid (Π) (9. Omg '0.040mmo 1 ), triphenylphosphine (3) 1.9mg, 0·121 6mmol ) of 1,4-dioxane (2 · 4 m 1 ) solution, 2M sodium carbonate aqueous solution (1.0ml, 2.00mmol) was added at room temperature, under nitrogen atmosphere, 80 ° After stirring for 3 hours, the mixture was allowed to cool to room temperature, and water was added to the reaction mixture, which was diluted with ethyl acetate. The aqueous layer was separated, and then the organic layer was dried over anhydrous magnesium sulfate. The residue obtained was purified by silica gel column chromatography (hexane: ethyl acetate = 20:1 to 10:1) to give pale yellow oil::-({[5-(2-methyl) 4-Nitrophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (-96-200918053 8 7.6 mg). MS ( ESI ) : 3 57 ( M+l ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.94-2.20 ( m, 4H ) 2.39 ( s, 3H) 2.46-2.61 ( m, 2H) 3.74 ( s, 3H ) 4.63 ( s, 2H) 6.79-6.8 7 ( m, 1H) 7.35 ( d, J = 8.0 Hz, 1H ) 7.55 ( dd, J = 8.3 Hz, 2.4 Hz, 1H) 8.03-8.18 ( m, 3H) ( 2) methyl 1-( { [ 5-(2-methyl-4-nitrophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate (8 7 mg, 0-244 mm〇l) To a suspension of reduced iron (135.6 mg, 2.44 mmol) in ethanol (1.7 ml) and water (0.174 ml), concentrated hydrochloric acid ( 0.0087 ml) was added at room temperature, stirred at 80 ° C for 2.5 hours, and allowed to cool. After the reaction mixture was diluted with ethyl acetate, the organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, and the organic layer was concentrated, and the obtained residue was chromatographed on a silica gel column [NH. Alkane: ethyl acetate = 7: 1 to 4: 1] Purified to give 1-({[4-(4-amino-2-methylphenyl))-yt-yl-2-yloxy) as a pale yellow oil. }Methyl)cyclobutanecarboxylic acid methyl ester (38.6 mg). MS ( ESI ) : 327 ( M+1 ) 1H NMR (3 00 MHz, CDC13) δ ppm 1.91-2.23 ( m, 7H ) 2.47-2.60 ( m, 2H) 3.61-3.71 ( br, 2H ) 3.73 ( s, 3H) 4.60 ( s, 2H ) 6.56-6.79 ( m, 2H) 6.74-6.79 ( m, 1H) 6.99 (d, J = 8.1 Hz, 1H) 7.51 ( dd, J = 8.4 Hz, 2.4 Hz, 1H ) 8.06 -8.09 ( m,1 H ) (Reference Synthesis Example 3 -1 2 ) -97- 200918053 1-( {[ 5-(4-Amino-3·fluorophenyl)pyridin-2-yl]oxy}methyl Manufacture of cyclobutanecarboxylic acid methyl ester [Chemical 8 5]

(1) In a solution of 2-fluoro-4-iodoaniline (2g, 8.44mmol) in tetrahydrofuran (10 ml) and toluene (1 〇ml), acetic anhydride (1.0 g, 10.13 mmol) and formic acid were added under ice cooling. The mixture of (1.9 g, 40.50 mmol) was added dropwise over 30 minutes, and the reaction mixture was warmed to room temperature and then stirred for 4 hours. The reaction mixture was diluted with ethyl acetate and washed with aqueous 1 N hydrochloric acid and saturated aqueous sodium carbonate. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and the obtained solid was suspended in a mixture of diethyl ether and hexane, and the solid was filtered to give a brown solid. -Fluoro-4-iodophenyl)carbenamide (2.2 g). MS ( ESI ) : 266 ( M+l ) 1H NMR (3 00 MHz, CDC13) δ ppm 7.41-7.53 ( m, 3H ) 8.13 ( t, J = 8.7 Hz, 1H) 8.48 ( d, J = 1.5 Hz, 1H) (2) N-(2-fluoro-4-iodophenyl)formamide (1.Og, 3.77 mmol), bis(pin ac o 1 at e) diboron (9 5 7.4 mg, 3.7 7 Mm o 1 ), palladium(II) acetate (42_3mg, 〇.19mmol), potassium acetate (l.lg, 1 1.32mmol) in dimethylformamide (25ml), stirred at 80 ° C under nitrogen atmosphere 3 · 5 hours, after cooling to room temperature, 200918053 water was added to the reaction solution, diluted with ethyl acetate, and the organic layer was washed with saturated brine. The organic layer was concentrated, and the obtained residue was applied to a column. Purification (developing solvent; hexane: ethyl acetate = 3 ··1 to 1 : 1) to give N-[2-fluoro-4-(4,4,5,5-tetramethyl- 1,3,2-Dioxaborolan-2-yl)phenyl]carboxamide (671.9 mg). MS ( ESI ) : 266 ( M+l ) , 264 ( Ml ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.34 ( s, 12H) 7.46-7.60 ( m, 3H) 8.36 ( t5 J = 7.9 Hz, 1H 8.48 ( s, 1H) (3 ) 1-{ 〔( 5-Bromopyridin-2-yl)oxy]methyl}cyclobutane residual acid methyl vinegar (690mg, 2_3mmol), N-[2-oxygen 4-(4,4,5,5-tetramethyl-1,3,2·dioxaborolan-2-yl)phenyl]carbenamide (672 mg, 2.53 mmol), palladium acetate (II) (5 1 . 6 mg, 0.2 3 mm ο 1 ), triphenylphosphine (180.9 mg, 0.69 mmol) in a solution of 1,4 - dioxin (14 ml), 2 M sodium carbonate aqueous solution was added at room temperature ( 5.8 ml, 11.50 mmol), stirred at 80 ° C for 3 hours under a nitrogen atmosphere, and allowed to cool to room temperature, then water was added to the reaction mixture, diluted with ethyl acetate, and the organic layer was concentrated. Column chromatography [developing solvent; hexane: ethyl acetate = 4:1 to 2: 1] crude purification, ethyl acetate and water were added to the residue, and hot-extracting was carried out at 60 °C. The organic layer was concentrated to give 1 -[({ 5 -[ 3 -fluoro-4-(methylamino)phenyl)pyridinium as a pale yellow oil. Methyl pyridine-2-yl}oxy)methyl]cyclobutanecarboxylate (58 2 2 m g ) <= MS (ESI): 3 5 9 ( M+l ) , 3 57 ( M-l )

1H NMR ( 3 00 MHz, CDC13) δ ppm 1.93-2.19 ( m, 4H -99- 200918053 ) 2.45 -2.5 8 ( m, 2H) 3.73 ( s, 3H) 4.62 ( s, 2H ) 6.78-6.85 ( in, 1H) 7.22-7.3 6 ( m, 2H) 7.43-7.56 ( br, 1H) 7.73 ( dd, J = 2.7 Hz, 8.6 Hz, 1H) 8.32 ( d, J = 2.7 Hz, 1H) 8.41 ( t, J = 8.6 Hz, 1H) 8.49 ( d, J = 1.2 Hz, 1H) (4) in l-[({5-[3-fluoro-4-(methylindolyl)phenyl]pyridin-2-yl} To a solution of methyl (meth)cyclobutanecarboxylate (220.4 mg, 0.615 mmol) in methanol (1.7 ml), EtOAc (EtOAc) After adding water, the mixture was neutralized by adding a saturated aqueous solution of sodium carbonate, and diluted with dichloromethane. The aqueous layer was separated, and the organic layer was dried over anhydrous magnesium sulfate, and then the mixture was concentrated, and the obtained residue was applied to the column. The residue was purified by EtOAc (EtOAc:EtOAc:EtOAc:EtOAc Oxymethyl}cyclobutanecarboxylic acid methyl ester (146.2 mg). MS ( ESI ) : 33 1 ( M+1 ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.89-2.19 ( m, 4H )2.44-2.59 ( m,2H) 3.72 ( s, 3H) 3.71-3.83 (br , 2H) 4.60 ( s, 2H ) 6.75-6.87 ( m, 2H ) 7.07-7.20 ( m,2H ) 7.69 (dd, J = 2.7 Hz , 8.6 Hz, 1H) 8.27 ( d, J = 2.4 Hz, 1H) (Reference Synthesis Example 3 -1 3 ) Production of methyl 1-( { [ 5-(4-amino-3-fluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylate - 100- 200918053 〔化86〕

According to the production method of Reference Synthesis Example (3-12), in (3), 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylic acid methyl ester was used instead of 1- {[(5-Bromopyridin-2-yl)oxy)methyl}cyclobutanecarboxylic acid methyl ester gives 1-({[4-(4-amino-3-fluorophenyl)pyrimidin-2-) Methyl]oxy}methyl)cyclobutanecarboxylic acid methyl ester. (1) 1-[({5-[3-Fluoro-4-(methylamino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester [Chemical 8 7 〕

Colorless solid MS (ESI): 3 5 8 ( Μ-1 ) 1H NMR (3 00 MHz, CDC13) δ ppm 1.99-2.24 ( m, 4H ) 2.51-2.60 ( m, 2H) 3.74 ( s, 3H) 4.69 ( s, 2H) 7.30-7.36 ( m, 2H ) 7.44-7.52 ( br, 1H) 8.46-8.51 ( m, 2H) 8.68 ( s, 2H ) (2 ) 1 - ( 5- ( 4-amino-3- Fluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester colorless solid MS (ESI) : 3 3 2 ( M + l )

1H NMR ( 3 00 MHz, CDC13) δ ppm 1.94-2.24 ( m, 4H -101 - 200918053 ) 2.50-2.5 9 ( m, 2H) 3.73 ( s, 3H) 3.81-3.95 ( br, 2H ) 4.66 ( s, 2H) 6.84-6.90 (m, 1H) 7.08-7.18 (m, 2H) 8.63 (s, 2H ) (Refer to Synthesis Example 3 -1 4 ) 1-( {[ 5-(4-Amino-2,5-) Manufacture of methyl difluorophenyl)pyridin-2-yloxy]methyl)cyclobutanecarboxylate [Chem. 8 8]

According to the production method of Reference Synthesis Example (3-9), 1-({[4-(4-amino) group) was obtained by substituting 4-bromo-2,5-difluoroaniline for 4-bromo-3-fluoroaniline. -2,5-Difluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester. (1) N-(4-bromo-2,5-difluorophenyl)formamide [Chem. 8 9]

Colorless solid MS (ESI): 23 8 (M+1), 23 6 ( Μ-1 ) 1 NMR (3 0 0 MHz, CDC13) δ ppm 7.29 -7.5 2 ( m, 1H )7.33 ( dd, J = 6.3 Hz, 9.8 Hz, 1H ) 8.32 ( dd, J = 7.2 Hz, 9.9 Hz, 1 H ) 8.43 -8.54 ( br, 1 H ) (2) l-[ ( {5-[2,5-Difluoro-4 -(formamidoamino)phenyl]-102 - 200918053 pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester [90]

Light yellow oil MS (ESI): 3 77 (M+l), 3 75 (Ml) 1H NMR (3 00 MHz, CDC13) δ ppm 1.91-2 ) 2.46-2.62 ( m, 2H ) 3.73 ( s, 3H ) 4.62 ( s, d, J = 9.0 Hz, 1 H ) 7.16 ( dd, J = 6.6 Hz, 11.1 Hz 7.60 ( br, 1H) 7.69-7.78 ( m, 1H) 8.23-8.35 8.50 ( d, J= 1 .2 Hz, 1H ) (3) 1-( { 〔5-(4-Amino-2,5-monochlorophenyl) oxy]methyl)cyclobutanecarboxylic acid methyl ester yellowish oil MS (ESI): 349 (M+l) 1H NMR (3 00 MHz, CDC13) δ ppm 1.90-2 ) 2.45 -2.62 ( m, 2H) 3.72 ( s, 3H) 3.80-3.97 4.61 ( s, 2 H 6_57 ( dd, J = 7_5 Hz, 11.4 Hz, 1H J = 0.8 Hz, 8.6 Hz, 1H ) 7.0 1 ( dd, J = 6.9 Hz, 11. 7.66-7.73 ( m, 1H) 8.22-8.2 8 ( m , 1H) (Reference Synthesis Example 3 -1 5 ) 1 - (Manufacture of methyl { { 5 - ( 4 -amino-3,5 -difluorophenyl)pyrimidin-2-yl)cyclobutanecarboxylate :.22 ( m,4H 2H ) 6.82 ( ,1 Η ) 7.47-(m, 2H ) 1 pyridine-2-yl.21 ( m, 4H (br, 2H ) ) 6.79 ( dd, 4 Hz, 1 Η ) Oxygen}methyl-103- 200918053 [Chemical 9 1]

Manufacture of 1-( { 〔5- (4-amine) by substituting 4-bromo-2,6-difluoroaniline for 2-fluoro-4-iodoaniline according to the method of Reference Synthesis (3 -13) Methyl-3,5-difluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylate. (1) N-(4-bromo-2,6-difluorophenyl)carbenamide [92]

Colorless powder MS ( ESI/APCI Dual ) : 23 4 ( Ml) 1H NMR ( 3 00 MHz, DMSO-D6) δ ppm 7.4 8-7.67 ( m, 2 H), 8.31 (s, 1 H), 9.85-10.05 (br,1 H) (2) N-[ 2,6-Difluoro-4-( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl Phenyl]carbamamine [93]

Colorless Amorphous MS ( ESI./APCI Dual ) : 2 84 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.34 ( s, 12 H), 7.40 ( d, J = 8.6 Hz, 2 H) , 8.77 ( d, J = 12.4 Hz, 1 H) (3) l-[({5-[3,5-Difluoro-4-(methylindolyl)phenyl]-104- 200918053 pyrimidine-2 -yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester

Colorless paste MS ( ESI/APCI Dual ) : 3 78 ( M+ 1 ) , 3 76 ( M-1 ) 1H NMR ( 3 00 MHz, DMSO-D6) δ ppm 1.79-2.19 ( m, 4 H) , 2.32-2.48 (m, 2 H) , 3.65 ( s, 3 H) , 4.64 ( s, 2 H ), 7.68 ( d, J = 9.0 Hz, 2 H), 8.34 ( s' 』1 H), 9.02 ( s, 2 H) , 10.04 ( s, 1 H) (4 ) 1-( {[ 5-(4-Amino-3,5-difluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylate Acid methyl ester colorless paste MS ( ESI/APCI Dual ) : 3 5 0 ( M + 1 ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.91-2.29 ( m, 4

H) , 2.46-2.63 (m, 2 H) , 3.73 ( s, 3 H) , 3.86 (br, 2 H ), 4.67 (s, 2 H) , 7.00 (dd, J = 7.1, 2.1 Hz, 2 H , 8.61 (s, 2 H ) (Reference Synthesis Example 4 - 1 ) 1-( { [ 5- ( 4- {[(4-nitrophenoxy)carbonyl]amino}phenyl)pyridine-2- Manufacture of methyloxy]methyl)cyclobutanecarboxylic acid methyl ester -105 - 200918053 [Chem. 9 5]

1-( { 〔5-(4-Aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester synthesized according to Reference Synthesis Example (3-1) ( 3.50 g, 11.2 In a solution of chloroform (70 ml), hydrazine (1.5 ml, 15.1 mmol) and 4-nitrophenyl chloroformic acid vinegar (2 _ 4 8 g, 1 2.3 mm ο 1 ) were added under ice cooling. The mixture was stirred for 3 hours under ice-cooling, and water was added to the mixture, and the mixture was evaporated, evaporated, evaporated, evaporated, evaporated, evaporated The residue obtained was washed with isopropyl ether to give 1-({[[4-(4-{[[4- 4-]]]]]]] Oxymethyl}cyclobutanecarboxylic acid methyl ester (5.24 g). MS ( ESI/APCI Dual ) : 478 ( M+1 ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1 .8 8-2.25 ( m, 4 H) 2.47-2.61 ( m, 2 H ) 3.73 ( s, 3 H) 4.63 ( s, 2 H ) 6.77-6.86 (m, 1 H) 7.01-7.11 (m, 1 H) 7.38-7.46 (m, 2 H ) 7.53 ( s, 4 H ) 7.78 ( dd, J = 8.63, 2.5 6 Hz, 1 H ) 8.26- 8-34 ( m, 2 H ) 8.36 ( dd, J = 2.49, 0.62 Hz, 1 H) (Refer to Synthesis Example 4-2) ( { 〔 5-( 4- Manufacture of methyl [[(4-nitrophenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylate-106- 200918053 [Chem. 9 6]

According to the production method of Reference Synthesis Example (4-1), 1-({[ 5-(4-aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester was used in place of 1 - ({[ 5-(4-Aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester to give 1-( { 〔 5- ( 4- { 〔 ( 4- Methylphenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester. 1 H NMR ( 3 00 MHz, CDC13 ) δ ppm 1 _ 0 3 - 1 _ 1 7 ( m, 2 H), 1.38-1.47 (m, 2 H), 3.70 (s, 3 H) , 4.57 (s, 2 H ), 7.17-7.25 ( br, 1 H) , 7.3 5 -7.46 ( m, 2 H) , 7.47-7.65 (m, 4 H) , 8.31 ( d, J = 8.9 Hz, 2 H) , 8.69 ( s, 2 H) (Reference Synthesis Example 4-3) 1-( {[ 5-(3 - nitro-4·{ 〔(4-nitrophenoxy)indolyl)amino}phenyl)pyrimidine-2 Manufacture of methyl-oxy)methyl)cyclobutanecarboxylic acid methyl ester [Chem. 9 7]

According to the production method of Reference Synthesis Example (4-1), 1-({[4-(4-amino-3-fluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid A was used. Substituting a methyl ester of 1-( { [ 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate to give 1-( { 〔 5- ( 3-fluoro 4-[[(-107-200918053 4-nitrophenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxaniummethyl)cyclobutanecarboxylic acid methyl ester. 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1 .96-2.26 ( m, 4 Η) 2.4 8 -2.63 ( m, 2 Η) 3.74 ( s, 3 Η) 4.70 ( s, 2 Η) 7.28-7.39 ( m, 3 Η) 7.40-7.48 ( m, 2 Η) 8.16-8.28 ( m, 1 Η) 8.28- 8.36 ( m, 2 Η) 8.70 ( s, 2 Η) (Refer to Synthesis Example 4-4) 1- ( Manufacture of {[ 5-(4-{4-[(4-nitrophenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester 〕

According to the production method of Reference Synthesis Example (4-1), 丨-(丨[5_(4-aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutane decanoic acid methyl ester was used instead of {[5-(4-Aminophenyl)pyridin-2-yl]oxanylmethyl)cyclobutanecarboxylic acid methyl ester to produce 1-( { 〔5-(4-{ 〔 (4 - nitro) Benzyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutylene_acid methyl ester. 4 Η 1 Η NMR ( 3 0 0 Μ Η z, CD C13 ) δ ppm 1.9 8 - 2.3 〇( m ' ) 2.50-2.65 ( m, 2Η) 3.75 ( s, 3Η) 4.70 ( s, 7.1 8 ( br, 1 Η ) 7.43 ( d, J = 9.5 Hz, 2H ) 7.54 ( d, J = 8 _9 H ' 2H) 7_60 ( d, J = 8.6 Hz, 2H) 8.32 ( d, J = 8.9 Hz, 2H) 8.7 ( s, 2H ) -108- 200918053 (refer to Synthesis Example 4-5) 1-(丨[5-(4-{[(4-nitrophenoxy)carbonyl]amino}phenyl)pyridin-2-yl Manufacture of methyl}methyl)cyclopropanecarboxylate methyl ester

Substituting 1-( { 〔 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester for 1-substance according to the production method of Reference Synthesis Example (4-1) ({[ 5-(4-Aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester, manufactured 1- ( { 〔 5- ( 4- { 〔 ( 4- Methyl phenoxy)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester. 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.08 ( dd, J = 4.2 Hz, 7.4 Hz, 2H) 1.41 ( dd, J = 4.2 Hz, 7.1 Hz, 2H) 3.72 ( s, 3H) 4.52 ( s, 2H 6.86 (d, J = 8.0 Hz, 1H) 7.05-7.14 ( br, 1H) 7.43 ( d, J = 9.2 Hz, 2H) 7.5 0-7.5 7 ( br, 4H) 7.80 (dd, J = 2.5 Hz, 8.8 Hz, 1H) 8.31 ( d, J = 9.2 Hz, 2H) 8.34 (d, J = 2.1 Hz, 1H ) (Refer to Synthesis Example 5) 1-( { 〔5-(4-{ 〔 (2 - Chlorine- Manufacture of benzyl 4-fluorophenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]amino}methyl)cyclobutanecarboxylate-109- 200918053

(1) Adding 2,2-cyclobutyl-3-oxopropionate benzyl ester in a solution of 5-bromopyrimidine-2-amine (187 mg, 1-07 mmol) in dimethylformamide (4 mL) (according to Org. Lett. 5,14, 2473-2475 (2003) synthesized (3 50 mg '1.61 mmol), added with difluoroacetic acid (ImL) and sodium triethoxypropoxyborohydride (l.〇) under ice cooling 6g, 5.00mmo 丨), while stirring at room temperature for 16 hours, a saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture under ice-cooling, and the reaction mixture was diluted with ethyl acetate, and the organic layer was washed with saturated brine. After drying the organic layer with anhydrous magnesium sulfate, the mixture was filtered and concentrated. The residue obtained was purified by silica gel column chromatography (developing solvent; hexanes: ethyl acetate = 9:1) to give 1-{[(5-bromopyrimidine) 2-Benzylamino]methyl}cyclobutanecarboxylic acid benzyl ester (261 mg). MS ( ESI ) : 3 78 ( M+l )

1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.90-2.12 ( m, 4H) 2.3 6-2.5 5 ( m, 2H ) 3.84 ( d, J-6.0Hz, 2H ) 5.16 ( s, 2H) 5.40-5.5 5 ( m, 1H) 7.25 -7.43 ( m, 5H) 8.22 ( s, 2H (2 ) in bis{[( 5-bromopyrimidin-2-yl)amino]methyl hydrazine Cyclobutanecarboxylic acid benzyl ester ( 1.42g, 3.77mmol) of 1,4-two chewing compound (30ml) was added to 4-(4,4,5,5-tetramethyl-1,3,2--110-200918053 under nitrogen atmosphere Dioxaborolan-2-yl)phenylamine (0.88g, 4.00mmol), triphenylphosphine (0.296mg, 1_13mmol), palladium acetate (Π) (〇_〇86g, 0.384mmol), then added 2M The sodium carbonate aqueous solution (9.5 ml) was stirred at 80 ° C for 1.5 hours, and the reaction solution was allowed to cool to room temperature, then diluted with ethyl acetate and water, and the aqueous layer was separated, and the organic layer was washed with saturated brine. After the addition, anhydrous magnesium sulfate and hydrazine were added and the mixture was allowed to stand, and the solid matter was filtered, and the filtrate was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (developing solvent; hexane: ethyl acetate = 2:1) Purification, diluting the obtained crude product with ethyl acetate, and using warm water (60 ° C) several times, The organic layer was dried over anhydrous magnesium sulfate, and the solid was filtered, and concentrated under reduced pressure to give an orange crystals of 1-({[4-(4-aminophenyl)pyrimidin-2-yl) Amyl}methyl)cyclobutanecarboxylic acid benzyl ester (1.18 g) MS (ESI): 3 89 (M+l) 1H NMR (3 00 MHz, CDC13) δ ppm 1.92-2.14 (m, 4H ) 2.40-2.56 ( m, 2H ) 3.67-3.82 ( br, 2H ) 3.91 ( d, J = 6.3Hz, 2H) 5.16 ( s, 2H) 5.3 4- 5.4 8 (m, 1H) 7.82-7.91 (m, 2H) 7.23-7.40 ( m, 7H ) 8.42 ( s, 2H ) (3 ) in 1-( {[ 5-(4-aminophenyl)pyrimidin-2-yl]amino}methyl)cyclobutane Add pyridine (0.046 ml, 0.569 mmol) and 4-nitrophenylchloroformic acid vinegar (86 mg, 0.428 mmol) to a solution of benzyl carboxylic acid (147 mg, 0.378 mmol) in chloroform (3 ml). After stirring for 1 hour at 〇 ° C, triethylamine (0-079 ml, 0.567 mmol) and 2-chloro-4-fluoroaniline (〇_〇 49 ml ^ 0.4 5 1 mmol ) were added to the reaction mixture to stir at 50 ° C. 4.5 hours, the reaction solution was diluted with ethyl acetate-111 - 200918053 ethyl ester, the organic layer was saturated aqueous ammonium chloride, saturated carbon After washing with an aqueous solution of sodium hydrogencarbonate and saturated brine, the organic layer was dried over anhydrous magnesium sulfate, and the solid was filtered, and the filtrate was concentrated, and the obtained residue was chromatographed on a silica gel column [NH oxime, developing solvent; hexane: acetic acid Purification of the ester = 2 : 1] afforded 1-({[4-(4-{[(2-chloro-4-fluorophenyl)aminocarbamoyl]amino}phenyl)pyrimidine- 2-Benzylamino}methyl)cyclobutanecarboxylic acid benzyl ester (155 mg). MS (ESI): 560 ( M+ 1 ) 5 5 8 ( Μ-1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.91-2.16 ( m, 4H) 2.38-2.56 (m, 2H) 3.93 (d, J = 6.3 Hz, 2H) 5.17 (s, 2H) 5_27 ( t, J = 6.2 Hz, 1H) 6_82 ( s, 1H) 6.98 ( s, 1H) 6.96-7.0 6 ( m, 1H) 7.12 ( dd, J = 2.9 Hz, 8.0 Hz, 1H) 7.28- 7.38 ( m,5H) 7.41-7.50 ( m,4H) 8.14 ( dd, J = 5.4 Hz, 9.0

Hz, 1 H ) 8.47 ( s, 2H ) (Example 1) 3-{ 〔5-(4-{ 〔(2-Methoxy-5-methylphenyl)aminomethylindenyl) Amino} Manufacture of phenyl)dark-2-yloxy}-2,2-dimethylpropanoic acid (Compound No. 1) (1) in 2-(1,3-oxacyclopentyl)·2 _Methylpropane-bupropanol (Reference patent document: W〇〇51〇2977) (45 3mg, 3 i〇mm〇i) of dimethyl ketoamine (in solution, add sodium hydride under ice cooling (add mobile stone) 45%), stir for 1 minute under ice cooling, and warm the reaction solution to room temperature'. Add 5 bromochloropyrimidine (2〇〇mg -112- 200918053 ' l.〇3mmol), stir at room temperature 3 0 In a minute, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. EtOAc (EtOAc m. Purification of ester = 1 0 : 1 to 2 : 1] afforded 5-bromo-2-[2-(1,3-dioxolan-2-yl)-2-methylpropoxy as a colorless solid Pyrimidine (1 7 7 mg) MS ( ESI/APCI Dual ) : 3 03 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.08 ( s, 6 H) 3.83- 3.91 (m, 2 H) 3.91-3.99 (m, 2 H) 4.21 (s, 2 H) 4.86 ( s, 1 H ) 8.52 ( s, 2 H ) (2 ) in 5-bromo-2-[ 2- (1,3-Dioxalan-2-yl)-2-methylpropoxy]pyrimidine (170 mg, 0.561 mmol), 4-nitrophenylboronic acid (1 8 7 mg '1.12 mmol) Add 10% palladium on carbon (8511^), and a mixture of triphenylphosphine (29mg '0_112mmol) in ethanol (1.7ml) and water (1.7ml), add sodium carbonate (476mg, 4.488mmol), external temperature 8 5 After stirring at °C for 4 hours, water and ethyl acetate were added to the reaction mixture, and the fluorite was filtered, and the ethyl acetate layer was extracted, dried (anhydrous magnesium sulfate), filtered, and concentrated to give the residue. Purification by sand column chromatography (developing solvent; hexane: ethyl acetate = 1 〇: 1 to 1:1) to give 2-[2-(1,3-oxo-oxo) as a pale yellow powder. Cyclo-2-yl)-2-methylpropoxy]-5-(4-nitrophenyl)pyrimidine (159 mg) MS (ESI/APCI Dual): 346 (M+l) 1H NMR (3 00 MHz, CDC13) δ ppm 1.12 ( s,6 Η) 3.84- 4.02 ( m, 4 H) 4.33 ( s, 2 H) 4.91 ( s, 1 H) 7.66- -113- 200918053 7.73 ( m, 2 Η) 8.32 -8.38 (m,2 Η) 8.77 ( s, 2 Η) (3) in 2-[2-(1,3-dioxol-2-yl)-2-methylpropoxy]-5- To a mixed solution of (4-nitrophenyl)pyrimidine (153 mg, 0.443 mm 〇l) in ethanol (2 ml) and tetrahydrofuran (1 ml), add +10% palladium on carbon (15 mg), and stir at room temperature under a hydrogen atmosphere. The reaction solution was filtered with celite, and the filtrate was concentrated, and the residue obtained was purified by silica gel column chromatography (hexane solvent: ethyl acetate = 8:1 to 1:2). 4 - { 2 -[ 2 - ( 1,3 -dioxacyclo-2-phenyl)-2-methylpropoxy]ha 11 疋-5-yl}aniline (i〇5mg) 〇MS ( ESI/APCI Dual ) : 3 16 ( M+l ), 3 14 ( M-1 ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.11 ( s, 6 H) 3.74- 3.85 (br, 2 H) 3.85-4.00 (m, 4 H) 4.27 (s, 2 H) 6.74- 6.81 ( m, 2 H) 7.28-7.34 ( m, 2 H) 8.63 ( s, 2 H) (4) at 4-{ 2-[2-(1,3-dioxol-2-yl)-2-methylpropoxy]pyrimidin-5-yl}aniline (7 3 4 mg, 2.3 27 mmol) in tetrahydrofuran (7.5 ml) In the solution, add triethylamine (0.324ml, 2.329mmol) 2,Methoxy-5-methylphenylisocyanate (9 6 9 mg, 5.818 mmol), stirred at room temperature for 20 hours, and the reaction mixture was concentrated, and the obtained residue was chromatographed with a silica gel column. [Expansion solvent; hexane: ethyl acetate = 8:1 to 1:1) was purified to give a colorless, non-crystalline 1-(4-{2-[2-(1,3-dioxolane)- 2-yl)-2-methylpropoxy]pyrimidine-5-yl}phenyl)-3-(2-methoxy-5-methylphenyl)urea (1.503 g). MS ( ESI/APCI Dual ) : 479 ( M+l) , 477 ( Μ - 1 ) 114- 200918053 1H NMR ( 300 MHz , CDC13 ) δ ppm 1.11 ( s, 6 Η) 2.31 ( s, 3 H) 3.82 ( s, 3 H) 3.84-4.00 ( m, 4 H) 4.29 ( s, 2 H) 4.91 (s, 1 H) 6.75-6.88 (m, 3 H) 7.13 (s, 1 H) 7.42-7.49 ( m, 2 H) 7.50-7.57 ( m, 2 H) 7.91-7.95 ( m, 1 H) 8.68 ( s, 2 H ) (5) at 1-( 4- {2-[ 2-( 1,3-dioxo) Heterocyclopentan-2-yl)-2-methylpropoxy]pyrimidin-5-yl}phenyl)-3-(2-methoxy-5-methylphenyl)urea (809 mg, 1.691 mmol) To a mixed solution of chloroform (9_7ml) and acetone (129ml), water (4.9ml) and p-toluenesulfonic acid monohydrate (4 8 3 mg, 2 _ 5 3 7 mm ο 1 ) ' at room temperature After stirring for 15 hours, water and ethyl acetate were added to the reaction mixture, and the mixture was filtered, and the ethyl acetate layer was filtered, and then dried (anhydrous magnesium sulfate), filtered, and concentrated, and the residue obtained was obtained by using the gum. Column chromatography [developing solvent; chloroform: ethyl g ethyl ester = 4: 1 to 2: 1] purification 'to obtain colorless amorphous 1 _ { 4 -[ 2 _ (2,2-dimethyl-3) -oxopropoxy)pyrimidin-5-yl]phenylindole_3_(2_ Methoxy-5-methylphenyl)urea (501 mg). MS ( ESI/APCI Dual ) : 43 5 ( M+l), 433 ( Ml ) 1H NMR ( 300 MHz, CDC13 ) δ ppm 1.26 ( s 6 H) 2.31 ( s, 3 H) 3.83 ( s, 3 H) 4.45 ( s, 2 H) 6.75-6.87 (m, 3 H) 7.10(s,1 H) 7.43-7.49(m,2 H) 7.5〇_757(m,2 H) 7.90-7.94 ( m, 1 H 8.68 ( s, 2 H) 9.7〇( s } H) (6) in { 4-[ 2-( 2,2-dimethyl-3-oxopropoxy)pyrimidin-5-yl]phenyl } -3- (2-methoxy-5-methylphenyl)urea (483mg, 1 _ 1 1 2 mm 01 ) in chloroform (19 m 1 ) solution, add m • chloro-115- under ice cooling 200918053 Perbenzoic acid (432mg, 2.50mmol), was stirred at room temperature for 15 hours, and the reaction mixture was concentrated, and the obtained residue was chromatographed on a silica gel column (developing solvent; chloroform:methanol = 30:1 to 1 5 : 1], and then purified by preparative thin-layer chromatography on silica gel [developing solvent; chloroform:methanol ==10:1] to give a pale yellow powder of 3-{[5-(4-{ 〔 ( 2-Methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]oxy} 2,2-dimethylpropanoic acid (23 mg). (Example 2) 3-{[5-(4-{[(2-methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]oxy} Production of 2-2,2-dimethylpropionic acid methyl ester (Compound No. 2) (1) 5-Bromo-2-chloropyrimidine (25.0 g, 125 mmol), 3-hydroxy-2,2-dimethyl Methyl propionate (33.4, 251111111〇1), potassium carbonate (34.7g > 251mmol), and tetra-n-butylammonium iodide (92.6g, 251mmol) of dimethylacetamide (500ml) were suspended. The mixture was stirred at ambient temperature for 4 hours, and the mixture was stirred for 3 hr. The solvent was developed; hexane:ethyl acetate = 15:1 to 3.5:1] was purified to afford 3-[(bromopyrimidin-2-yl)oxy]-2,2-dimethylpropanoic acid as a colorless powder. Base ester (17.48 g). MS ( ESI/APCI Dual ) : 289 ( M+1 ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.34 ( s, 6 Η) 3.70 (s, 3 Η) 4.37 (s, 2 Η) 8.52 (s, 2 Η) -116- 200918053 (2) 3-[(5-Bromopyrimidin-2-yl)oxy]-2,2-dimethylpropionic acid methyl ester (17.4g, 60.14mmol), 4-nitrate Phenylboronic acid (ll. 4g, 66.16mmol), palladium acetate (1.35g, 6.01mmol), and triphenyl phenyl (4_73g, 18.04mmol) of 2M sodium carbonate aqueous solution (150 ml), dioxins The mixture of the alkane (350 ml) was stirred at 80 ° C for 30 minutes, and water was added to the reaction mixture, and ethyl acetate was added to the mixture. The ethyl acetate layer was filtered, and then dried (anhydrous magnesium sulfate) and filtered. After concentrating, the obtained residue was purified by a silica gel column chromatography (developing solvent; hexane: ethyl acetate = 8:1 to 1:3) to obtain a 2,2-dimethyl group as a yellow powder. 3-{[5-(4-Nitrophenyl)pyrimidin-2-yl]oxy}propionic acid methyl ester (16.87 g). MS ( ESI/APCI Dual ) : 3 3 2 ( M+ 1 ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.38 ( s,6 Η) 3.72 ( s, 3 H) 4.48 ( s, 2 H) 7.67-7.73 ( m, 2 H) 8.33-8.39 ( m5 2 H ) 8.77 ( s, 2 H ) (3 ) in 2,2-dimethyl-3-{[ 5-(4-nitrophenyl)pyrimidine-2 -Methoxypropionic acid methyl ester (16.87g, 50.9mmol) of a mixed solution of methanol (200 in 1) and tetrahydrofuran (200 m 1 ) was added with 丨〇% platinum carbon (1.69). g) 'Stirring at room temperature for 20 hours under a hydrogen atmosphere, the reaction solution was subjected to filtration of fluorite, and the filtrate was concentrated by a column chromatography using a gel column chromatography [developing solvent; hexane: acetic acid Ester: 1 to 丨: 5] Purified 'to give a pale yellow powder of 3-{[5-(4-aminophenyl)pyran-2-yl]oxy}-2,2-methylpropanoic acid Base ester (14.2 §). MS (ESI/APCI Dual) : 3〇2 (M+1) , 300 (M-1) -117- 200918053 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.36 ( s, 6 H) 3.71 (s, 3 H) 3.75-3.88 (br, 2 H) 4.42 (s, 2 H) 6.74-6.81 (m, 2 H) 7.28-7.35 (m, 2 H) 8.63 ( s, 6 H) (4 ) at 3_丨[5-(4-Aminophenyl)pyrimidin-2-yl]oxy} _ 2,2-dimethylpropanoic acid methyl ester (6.00 g, 19.91 mmol) in tetrahydrofuran (60 ml) Amine (2.78 ml, 19.91 mmol), 2-methoxy-5-methylphenylisocyanate (8.29 g, 49.78 mmol), stirred at room temperature for 3.5 hours, and concentrated. The residue was purified by silica gel column chromatography (developing solvent: hexane: ethyl acetate = 4:1 to 1: 4) to afford 3-yel. Oxy-5-methylphenyl)aminomethylindolyl]amino}phenyl)pyrimidine-2-yloxy}-2,2-methylpropionic acid methyl vinegar (9.27 g). (Example 3) According to the production method of Example 2, 2-methoxy-5 was replaced by using 2-ethylphenyl isocyanate, 2,3-dimethoxyphenyl isocyanate or 2-chlorophenyl isocyanate. -Methylphenylisocyanate' gives the following compound of the invention σ 3_{ [5-(4-{ 〔(2-ethylphenyl)aminomethylindenyl)amino benzene

No. 3) 3-{[5-(4-{ 〔(2,3-dimethoxyphenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]oxy} -2,2 -Dimethylpropionic acid methyl vinegar (Compound No. 4) -118- 200918053 3-{[5_(4-{ 〔(2-Chlorophenyl)aminomethylindenyl)amino}phenyl)pyrimidine-2 -yl}oxy}-2,2-dimethylpropionic acid methyl ester (Compound No. 5 (Example 4) [5-(4-{ 〔(2-methoxy-5-methylphenyl)amino) Mercapto]amino}phenyl)pyrimidin-2-yloxy}.2,2-dimethylpropanoic acid (Compound No. 1) was produced in 3-{ [5-(4-{ 〔 (2- Methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)-p-thyl-2-yloxy}-2,2-dimethylpropionic acid methyl ester (9.25 g, 19-9 mmol) To a mixed solution of tetrahydrofuran (90 ml) and methanol (90 ml), a 6 M aqueous sodium hydroxide solution (3 3 ml) was added, and the mixture was stirred at room temperature for 2 hours, and a 1 M aqueous solution of hydrochloric acid was added to the reaction mixture under ice cooling. After extracting with ethyl acetate, drying (anhydrous magnesium sulfate) was filtered and concentrated, and the residue obtained was chromatographed on a silica gel column (developing solvent; chloroform:methanol = 5:1 to 12: 1] Purification, recrystallization from aqueous ethanol' to give 3-{[5-(4-{[(2-methoxy-5-methylphenyl))amino]alkyl) as a colorless powder }Phenyl)picky-2-yl]oxyj 2,2-dimethylpropionic acid (5.8 (^). (Example 5) According to the production methods of Example 2 and Example 4, the following Inventive compound. 3_丨[5_(4·([2,ethylphenyl)aminocarbamimidyl]amino benzene-119- 200918053 base) acridine·2_yl]oxy} _2,2- Dimethylpropionic acid (Zeta 3-{[5-(4-{ 〔(2,3-dimethoxyphenyl)amino}phenyl)pyrimidin-2-yl]oxy} -2,2 - Dimethylpropane 7) 3_{[5_(4_丨[(2-chlorophenyl)aminocarbamimidyl)pyrimidin-2-yl]oxanthene-2,2-dimethylpropanoic acid (compound ( Example 6) 3-{[5-(4-{[(3,4-dimethylphenyl)carbonyl)pyrimidin-2-yl]oxy}-2,2-dimethylpropanoic acid methyl ester ( Manufactured in a solution of 3-{[5-(4-aminophenyl)pyrimidin-2-yl]propanoic acid methyl ester (86 mg, 0.285 mmol) in tetrahydro I, triethylamine under ice cooling (〇· 1 2 0 m 1 , C 3,4 - methyl peroxide, chlorine (96 mg, 0.570 mmol) 5 · 5 hours, after adding 1 Μ hydrochloric acid aqueous solution to the reaction mixture, extracting, drying (anhydrous magnesium sulfate), filtering, and concentrating the residue by chromatography on a silica gel column (developing solvent; =1 = 〇: 1 to 1 : 2] Purification to obtain {[(3,4-dimethylphenyl)carbonyl]amino}phenyloxy}-2,2-dimethylpropanoic acid methyl ester (44!^) as a colorless powder. ). (Example 7) 3_{[5-(4-{[(3,4-dimethylphenyl)carbonyl) No. 6) Methylmercapto]amine (Compound) Amino]Phenyl No.8 )]amino}phenyl compound No. 9 Oxygen}-2,2-dimethyl ketone (1 · 5 m 1 ) .8 5 5 mm ο 1 ) and stirred at room temperature with ethyl acetate By alkane: ethyl acetate 3-{[5-(4-)pyrimidin-2-yl]]amino}phenyl-120-200918053)pyrimidin-2-yloxy}-2,2-di Methylpropionic acid (Compound No. 10) was produced from 3-{[5-(4-{[(3,4-dimethylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy} -2,2-Dimethylpropionic acid methyl ester (9 2 mg, 0.212 mmol) in a mixture of tetrahydrofuran (2 ml) and methanol (2 ml), 6 m aqueous sodium hydroxide (0.35 ml, 2.1 2 mmol) After stirring at room temperature for 4 hours, a 1 Μ aqueous hydrochloric acid solution was added to the reaction mixture under ice-cooling, and extracted with ethyl acetate, and then dried (MgSO. Chromatography [developing solvent; chloroform:methanol = 50: 1 to 12: 1], using hexane: acetic acid The mixed solvent of the ester = 1 : 10 was washed to obtain 3-{[5-(4-{[(3,4-dimethylphenyl)carbonyl]amino}phenyl) phenyl group- 2-yl]oxanthene-2,2-methylpropionic acid (48 mg). (Example 8) 3-{[5-(4-{[(2,3-Dimethoxyphenyl)aminomethionyl]amino}phenyl)pyrimidin-2-yl]oxy} -2 -(Hydroxymethyl)-2-methylpropionic acid ethyl ester (Production of Compound No. 1 (1) 3-ethyl-2-(hydroxymethyl)-2-methylpropionic acid ethyl ester (reference patent Literature: ^02006051662) (596mg, 3.083mmol), 5-bromo-2-chloropyrimidine (l_〇〇g, 6.17mmol), potassium carbonate (852mg, 6.17mmol), and tetra-n-butyl valence ( 2.32 g, 6.17 mmol) of a suspension of dimethylacetamide (1 2 m 1 ) at an external temperature of i 4 〇. (: stirring for 3 hours, adding water to the reaction solution, extracting with ethyl acetate, drying (anhydrous -121 - 200918053 magnesium sulfate), filtered, and concentrated, the residue obtained was purified by column chromatography (hexane solvent: ethyl acetate = 8:1 to 1:1). 3-[(5-Bromopyrimidin-2-yl)oxy]-2-(hydroxymethyl)-2-methylpropanoic acid ethyl ester (318 mg) as a yellow solid. MS ( ESI/APCI Dual ) : 3 19 ( M+1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.27 ( t, J = 7.2 Hz, 3 H) 1.31 ( s, 3 H) 2.65-2.73 ( m, 1 H ) 3.73 -3.88 ( m, 2 H) 4.21 ( q, J = 7.2 Hz, 2 H) 4.45 ( d, J = 10.9 Hz, 1 H ) 4.67 ( d, J = 1 0.9 Hz, 1 H) 8.53 ( s, 2 H ) (2 ) ethyl 3-[( 5-bromopyrimidin-2-yl)oxy]-2-(hydroxymethyl)-2-methylpropanoate (293mg, 0.918 In a solution of chloroform (5 ml), t-butyldimethylchloromethane (277 mg, 1 , 8 3 6 mmol), imidazole (1 87 mg, 2.7 5 4 mm ο 1 ) were added to the chamber under ice cooling. After stirring for 15 hours, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. Then, the mixture was washed with a 0.5 hr of aqueous hydrochloric acid, a saturated aqueous solution of sodium carbonate and brine, dried (MgSO4), filtered and concentrated. The obtained residue was purified by silica gel column chromatography (yield: hexane: ethyl acetate = 10:1) to give 3-[( 5-bromopyrimidin-2-yl) _2_({[[t-butyl(dimethyl)methyl)alkyl]oxy}methyl)-2-methylpropanoic acid ethyl ester (3 5 2 mg). MS ( ESI/APCI Dual ) : 43 3 ( M+1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 0.00 ( s, 3 H) 0.01 ( s, 3 H) 0.84 ( s, 9 H) 1.25 ( t , 1 = 1.2 Hz, 3 H) 1.29 ( s, 3 H) 3.76-3.81 (m, 1 H) 3.87-3.92 (m, 1 H) -122- 200918053 4.12-4.21 ( m, 2 Η) 4.46-4.56 ( m} 2 Η) 8.54 ( s, 2 Η) (3) 3 -[(5-Dip-deep-2-yl)oxy]-2-( { 〔t-butyl(dimethyl)metholane Ethyloxy}methyl)_2-methylpropionic acid ethyl ester (669mg, 1.544mmol), 4_nitrophenylboronic acid (2 8 3 mg, 1.698mmol), acetic acid (II) (35mg ' 0.154 Mixture of 2M sodium carbonate aqueous solution ( 3.86 ml) and dioxane (1 3 · 4 m 1 ) of triphenylphosphine (121 mg, 〇. 463 mmol), and stirring at an external temperature of 8 〇〇c for 5 minutes. Water and ethyl acetate were added to the reaction mixture, and the mixture was filtered, and the ethyl acetate layer was filtered, dried (MgSO4), filtered, and concentrated, and the residue obtained was chromatographed by column chromatography. The solvent was developed; hexane: ethyl acetate = 4: 1] purified to afford 3 - {[t-butyl(dimethyl)methyl)alkyl] Methyl-2-({(5-(4-nitrophenyl)pyrimidin-2-yl)oxy}methyl)propanoate (680 mg) MS ( ESI/APCI Dual ) : 476 ( M +l ) 1H NMR ( 300 MHz, CDC13 ) δ ppm 0.0 1 ( s, 6 H ) 0.84 ( s, 9 H) 1.25 ( t, 1 = 1.2 Hz, 3 H) 1.32 ( s, 3 H) 3.79-3.84 ( m, 1 H) 3.90-3.95 ( m, 1 H) 4.12-4.22 ( m, 2 H) 4.56-4.66 (m, 2 H) 7.67-7.73 (m, 2 H) 8.33-8.39 ( m, 2 H 8.77 ( s, 2 H ) (4) on 3-{ [t-butyl(dimethyl)methyl decyloxy] _2-methyl-2- ({[( 5-(4-nitrobenzene) Addition of 10% hydrazine carbon to a mixed solution of methyl (pyridin-2-yl)oxy]methyl}propionic acid ethyl vinegar (670 mg, 1.409 mmol) in methanol (3.5 ml) and tetrahydrofuran (3 · 5 m 1 ) (6 7 mg), stirred at room temperature for 20 hours under a hydrogen atmosphere, and the reaction solution was subjected to a fluorine filtration of -123-200918053. The filtrate was concentrated by chromatography, and the obtained residue was chromatographed with silica gel. Alkyl: ethyl acetate = 2: 1] Purified to give 3-{[( 5-(4-aminophenyl)pyrimidin-2-yl]oxy ({[[-butyl] Carbenyl]oxy}methyl)-2-carboxylic acid Ethyl ester (412 mg). MS ( ESI/APCI Dual ) : 446 ( M+l ) , 444 ( Ml ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 0.00 ( s, 6 0.84 ( s, 9 H) 1.25 ( t, J = 7.2 Hz ,3 H) 1.31 ( s, 3 3.77-3.95 (m, 4 H) 4.11-4.22 (m, 2 H) 4.50-4.61 (H) 6.76-6.82 ( m, 2 H) 7.29-7.3 5 ( m, 2 H) 8.64 ( s, ) (5 ) in 3 - {[( 5-(4-aminophenyl)pyrimidin-2-yl)i 2-( { 〔t-butyl(dimethyl)carbamyl) Ethyl}ethyl)-2-propionic acid ethyl ester (410 mg, 0.92 mmol) in chloroform (23 ml) was added, and pyridine (〇················ , 1.58 mmol), stirred at room temperature for 1.5 hours under ice cooling, and then added triethylamine (〇.256 ml, 1.84 mmol), 2,3-oxyaniline (1 5 5 mg, 1. 〇1 2 mm ο 1 ) Adding water to the reaction mixture at room temperature, and adding water to the reaction mixture, extracting with ethyl acetate, and then washing with 1.5 M sodium hydrogen carbonate solution, 1 Μ aqueous hydrochloric acid solution, saturated sodium carbonate aqueous solution and saturated brine, and drying (anhydrous magnesium sulfate) After filtration, concentration, the residue obtained is purified by column chromatography (developing solvent; ethyl hexane acid = 3: 2). To a colorless amorphous 3-{ 〔 t· (dimethyl)methanyloxy} -2-( {[ 5-(4- {[2,3-column to yellow] -2-ylpropane H) H) m, 2 2 Η % ) - phenyl group in methyl liquid, dimethyl group, oxidation and food, borrow: ethyl butyl dimethyl-124- 200918053 oxyphenyl) aminomethyl decyl amide Ethyl phenyl)pyrimidin-2-yl]oxy}methyl)-2-methylpropanoic acid ethyl ester (476 mg). MS ( ESI/APCI Dual ) : 625 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 0.〇〇( s, 6 H) 0.84 ( s, 9 H) 1.25 ( t, J = 7.2 Hz , 3 H) 1.31 ( s, 3 H) 3.79-3.94 (m, 8 H) 4.11-4.22 (m, 2 H) 4.52-4.64 (m, 2 H) 6.64-6.69 (m, 1 H) 7.02-7.10 (m, 2 H) 7.40( s, 1 H ) 7.45-7.51 (m, 2 H) 7.53-7.59 (m, 2 Η) 7·73_7·78 (m, 2 H ) 8.69 ( s, 2 H ) ( 6) 3-{ [t-butyl(dimethyl)methyl sylvestre oxime-2· ({ 〔5-(4-{ 〔2,3-methoxyphenyl]amino) To a solution of ethylamino)phenyl]pyrimidin-2-yl}oxy)methyl)-2-methylpropanoate (47 mg) in tetrahydrofuran (5 ml) at room temperature - Butyl ammonium fluoride (1.5 ml, 1 · 5ιηπιο1) 'Stirring under ice-cooling for 15 hours, adding water to the reaction mixture', extracting with ethyl acetate, drying (anhydrous magnesium sulfate), filtering, concentrating, lending The obtained residue was purified by a silica gel column chromatography (developing solvent; chloroform:methanol = 15:1) to afford 3-{[(4-([ Phenyl)aminomethylmercapto]amino}phenyl)pyrimidine-2_ Ethyloxy-2-(hydroxymethyl)-2-methylpropanoic acid ethyl ester (243 mg). (Example 9) 3-{ [ 5-(4-{ 〔(2,3-dimethoxyphenyl)aminomethylindolyl)amino phenyl)pyrimidin-2-yl]oxy} -2 -(Hydroxymethyl)-2-methylpropionic acid-125-200918053 (Compound No. 12) was produced from 3-{[4-(4-{[[2,3-dimethoxyphenyl]] Addition of 6M Hydrogen Oxide (0.78) to a mixed solution of ethyl phenyl)pyrimidin-2-yloxy]ethyl-2-(hydroxypropionic acid ethyl ester (240 mg, 0-47 mmol) in tetrahydrofuran and methanol (5 ml) Mg), stirring at an external temperature of 60 ° C for 1 hour, adding 1 Μ hydrochloric acid aqueous solution to the reaction, and concentrating, the obtained residue was chromatographed [developing solvent; chloroform: methanol: 2 5 % aqueous ammonia = 5 0 : :1 : 〇] Purification, washing with hexane:ethyl acetate = 1 :1 to give 3 -{[5-(4-dimethoxyphenyl)aminomethylindenyl]amino}benzene as a colorless powder Pyrimidine-2-(hydroxymethyl)-2-methylpropanoic acid (56 mg). (Example 1 〇) 3-[(5-{4-[(3,4-dimethylphenyl)) Manufacture of methylaminopyrimidin-2-yl)oxy]-2,2-dimethylpropanoic acid methyl ester (alias) (1) 3-[(5-bromopyrimidin-2-yl)oxy] 2 , 2 - methyl ester (l_80g, 6.22mmol), 4·carboxyphenyl boron | 6.22mmol ), and triphenylphosphine palladium (3 5 9 mg, 0.2 0.4M sodium carbonate solution (30ml), acetonitrile (30ml) The mixture was stirred for 2 hours at an external temperature of 1 ° C, and 1 M was added to the reaction mixture, and the mixture was extracted with chloroform, and then dried (MgSO4). Base methyl hydrazine methyl)-2-methylpyran (10ml) sodium sulphate solution in ice-cooled with a sulphuric acid column 10: 1 to 5 〇 mixed solution -{ ((2,3-deep-2 ·yl)oxy 】Phenyl} ¥1 3 Mixture of dimethyl dimethyl propionate (l. 〇 3g, S 1 mm ο 1 ), with aqueous hydrochloric acid, concentrated, chloroform: -126- 200918053 Methanol = 2 〇 : 1) Purification to give 4-[2-(3-methoxy-2,2-dimethyl-3-oxopropoxy) pyridine-5-yl]benzoic acid (1.33 g) as colorless powder. ° MS ( ESI/APCI Dual ) : 33 1 ( M+l ) , 329 ( Ml ) 1H NMR ( 300 MHz , CDC13 ) δ ppm 1.38 ( s, 6 H) 3.72 ( s, 3 H) 4.48 ( s, 2 H) 7.62-7.67 ( m, 2 H) 8.20-8.26 (m, 2 H) 8.78 (s, 2 H) (2) in 4_[ 2- (3-methoxy Benzyl-2,2-dimethyl-3-oxopropoxy)acridin-5-yl]benzoic acid (420 mg, 1.27 mmol) in dimethyl ketoamine (5 m 1 ) solution Add 1 · ( 3 -Dimethylaminopropyl)_ 3 _ ethylcarbo-imine hydrochloride ( 366 mg, i.91 mmol) ' 1-Phenylbenzoxazole (51 mg, 038 mmol), 3, 4 -Dimethylaniline (185 mg, 53 mmol) was stirred at room temperature for 1 hour, water was added to the reaction mixture, and after washing with chloroform, 'washed (water, saturated brine)), dried (no sulfur sulphur 13⁄4 mg) After filtration, concentration, and recrystallization from the acetic acid vinegar to obtain 3-[(5-{4-[(3,4-dimethylphenylamino)]phenyl} Pyrimidin-2-yl)oxy]-2,2-dimethylpropionic acid methyl ester (3 65 mg). (Example 1 1 ) , [(5-丨4_[(3,4-Dimethylphenyl)aminomethylindenyl]phenyl}-denyl 2)oxy]-2,2-dimethylpropane The acid (Compound No. 14) was produced by 3-[(5_丨4-[(3,4~dimethylphenyl)aminocarbamimidyl]-127- 200918053 phenyl}pyrimidin-2-yl)oxy] -2,2-Dimethylpropionic acid methyl ester (348 mg, 0.80 mmol) in a mixture of tetrahydrofuran (4 ml) and methanol (4 ml), 2M aqueous sodium hydroxide (4 ml, 8 mmol) After stirring at a temperature of 60 ° C for 30 minutes, the reaction solution was allowed to cool, and then a 1N aqueous solution of hydrochloric acid was added thereto, and the mixture was extracted with ethyl acetate, washed (water, saturated brine), dried (anhydrous magnesium sulfate), After filtration and concentration, the obtained residue was purified by silica gel column chromatography (developing solvent; chloroform:methanol = 50:1), and recrystallized from ethanol to give 3-[(5 - { 4-[(3,4-Dimethylphenyl)aminocarbamoyl]phenyl}pyrimidin-2-yl)oxy]-2,2-dimethylpropanoic acid (1〇2111§). (Example 1 2 ) 3-{ 〔5-(4-{ 〔(2-methoxy-5-methylphenyl)aminomethylindenyl)amino}phenyl)pyrimidin-2-ylylamine Manufacture of (1) 2-amino-5-bromopyrimidine (84.4 mg, 0-48 5 mmol) in dimethylformamide (5 ml) In the solution, benzyl 2,2·dimethyl-3-oxopropionate was added under water cooling (according to the literature: 〇rg. Lett. 20 03, 5, 14, 2473-2475) (200 mg, 0.970 mmol) , trifluoroacetic acid (6 6 4 mg ' 5.8 2 mm ο 1 ), and sodium triethoxy hydroxy borohydride (411 mg, 1.94 mmol), stirred at room temperature for about 1 day, adding triethoxy hydrazine Sodium sulphate (200 mg, 0.944 mmol) was stirred at 40 ° C for 5 hours at room temperature. After cooling to room temperature, water was added and the mixture was diluted with ethyl acetate. After washing with saturated brine, the organic layer was dried over anhydrous magnesium sulfate, dried and concentrated, and the obtained residue was chromatographed on a silica gel column (developing solvent; hexane: ethyl acetate 2: 1 to 4: 1] Purification to give 3-[( 5-bromo) 2-yl) amino] -2,2-dimethyl-propionic acid benzyl ester (98.4 «1§). MS ( ESI ) : 3 64 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.26 ( s, 6H ) 3.5 0-3.62 ( m, 2H ) 5.12 ( s, 2H) 7.20-7.43 ( m, 5H) 8.24 (s, 2H) (2) Benzyl 3-(( 5-bromopyrimidin-2-yl)amino]-2,2-dimethylpropanoate (98.4 mg, 0.270 mmol), 4 -Nitrophenyl decanoic acid (50 mg '0.297 mmol), acetic acid pin (6.1 mg, 0.027 mmol) of 'triphenylphosphine (21_3 mg, 0.081 mmol) in dioxane (2 ml), added at room temperature 2M sodium carbonate aqueous solution (〇.676ml, 1.35mm〇l), stirred at 80 ° C for 2 hours under nitrogen atmosphere, and then allowed to cool to room temperature, the reaction solution was diluted with chloroform, and the organic layer was mixed with water and saturated salt. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated, and the obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4:1 to 2:1). 2,2-Dimethyl-3-{[ 5-(4-nitrophenyl)pyrimidin-2-yl]amino}propionic acid benzyl ester (54.4 mg) was obtained. MS ( ESI ) : 407 ( M+ 1 ) (3 ) benzyl 2,2-dimethyl-3-indole[5-(4-nitrophenyl)pyrimidin-2-yl]amino}propanoate ( 54.4mg, 0.13 4mm〇l) in ethanol (2ml) solution, water (0.1ml), iron powder (37.4mg, 0.669mmol), concentrated hydrochloric acid (Ο · Ο Ο 5 m 1 ), to 80 ° C Stir for 30 minutes -129- 200918053, add iron powder (37.4mg, 0.669mmol), concentrated hydrochloric acid (0_005ml) 'stirred at 90 °C for 30 minutes, let the reaction solution cool to room temperature, then use magnesium fluoride The solid was removed by filtration, and the solid was concentrated, and the residue was diluted with ethyl acetate and aqueous sodium hydrogen carbonate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine and dried over anhydrous magnesium sulfate After the layer, it was filtered, concentrated, and quantitatively obtained benzyl 3-(4-(4-aminophenyl)pyrimidin-2-yl]amino}-2,2-dimethylpropanoate. MS ( ESI ) : 3 77 ( M+l ) (4) 3-{[ 5-(4-Aminophenyl)pyrimidin-2-yl]amino}-2,2-dimethylpropanoic acid benzyl To a solution of the ester (50.411^, 0.13 4111111〇1) in tetrahydrofuran (1 ml), 2-methoxy-5-methylphenylisocyanate (0.0393 ml, 0.268 mmol) was added and stirred at room temperature for 1 day. The liquid was diluted with ethyl acetate, and the organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then filtered and concentrated, and the obtained residue was chromatographed on a silica gel column (developing solvent; hexane: acetic acid Ethyl ester = 1 : 1] purified to give 3-{[5-(4-{[(2-methoxy-5-methylphenyl)aminocarbamoyl]amino}phenyl)pyrimidine-2 -yl]amino}-2,2-dimethylpropionic acid benzyl vinegar (46.7 mg). MS (ESI): 540 (M+1), 538 (M-1) (5) ??? 3-{[5-(4-{[(2. methoxy-5-methylphenyl)amino) Thio[]amino}phenyl)pyrimidin-2-yl]amino}-2,2-dimethylpropionic acid benzyl ester (46.7 mg, 0.0865 mmol) in tetrahydrofuran (2 ml), and methanol (2 ml) To the mixed solution, a 6 M aqueous sodium hydroxide solution (1 m 1 ) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was added with 1 Μ -130-200918053 aqueous hydrochloric acid solution and diluted with ethyl acetate to saturate the organic layer. After the brine was washed, the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated, and the resulting solid was suspended in ethyl acetate/isopropyl acetate, and the solid was filtered to give a colorless solid. [ 5-( 4_丨纟(^methoxy-5-methylphenyl)aminomethylindolyl]amino}phenyl) Chelate-deep 2-yl]amino} -2,2-dimethyl Propionic acid (31.8 mg). (Example 1 3) According to the production method of Example 12, the following compound of the present invention was obtained by substituting 2-methoxyphenyl isocyanate for 2-methoxy-5-methylphenylisocyanate. 3-{[5-(4-{ 〔(2-Chlorophenyl)aminomethylindolyl)amino phenyl)pyrimidin-2-yl]aminopurine·2,2-dimethylpropanoic acid ( Compound No. 16) (Example 1 4 ) 3- { 〔5-(4-{ 〔(2,3-Dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyrimidin-2-yl Production of Aminoguanidine-2,2-dimethylpropionic acid (Compound No. 17) (1) on 3-{[4-(4-aminophenyl)pyrimidin-2-yl]amino}-2 , a solution of benzyl 2-dimethylpropionate (131 mg, 0.34 8 mmo1) in chloroform (2.6 ml) was chilled under ice-cold (0-0423 ml, 0.522 mmol), and 4-nitrophenyl Chloroformate (84.2 mg, 〇.418mmo1) 'stirred at room temperature for 1 hour' was added triethylamine (0.0 7 2 8 m 1 , 〇.522 mmol) and 2,3-dimethoxy to the reaction mixture. The aniline (0_0562ml, -131 - 200918053 0-418mm〇l) was stirred at room temperature for a while, the reaction solution was diluted with B, and the organic layer was washed with a saturated aqueous solution of ammonium chloride, saturated aqueous sodium chloride and brine. After drying over anhydrous magnesium sulfate, filtration, concentration and chromatography on a silica gel column [NH. =1 : 1] Purification to give 3 - { 〔5-((2,3-dimethoxyphenyl)aminomethylindenyl)amino}phenyl)yl]amino} -2,2·2 Benzyl methacrylate (97.3 mg). MS (ESI): 556 (M+l), 554 (Ml) (2) 3-{[5-(4-{[(2,3-dimethoxyphenylmethyl)amino}benzene Addition of 6 hydrazine to a mixed solution of tetrahydrofuran (2m) methanol (1 m 1 ) in a pyrimidine-2-yl]amino}-2,2-diacid benzyl ester (97.3 mg, 0-175 mmol) Sodium hydroxide water (0.5 ml) was stirred at room temperature for 1 hour, and the reaction mixture was neutralized with a 1 M solution, diluted with ethyl acetate, and the organic layer was washed with saturated water and then concentrated. Ethyl acetate was solidified, and the solid was filtered to give 3-{[{[(2,3-dimethoxyphenyl)aminocarbamoyl]amino}phenylidin-2-yl] as a colorless solid. Amino}-2,2-dimethylpropionic acid (64.6 mg). (Example 1 5) 2-{[5-(4-{[(2-methoxy-5-methylphenyl)amine) Preparation of ethylmethylamino}phenyl)pyrimidin-2-yloxy]-2-methylpropanoate ethyl ester No. 1 8 ) (1) 5-bromo-2-hydroxypyrimidine (2.0 g, 1 1.4) Methyl) sodium hydrogen urate organic layer open solvent 4-{[pyrimidine-2 -)aminomethylpropane.), and solution (hydrochloric acid brine suspended in 5-(4-yl)pyrimidinyl 〕 (In the solution of dimethyl-132- 200918053 methotrexate (6 〇ml), add ethyl 2-bromoisobutyrate (2.9g, 1 4.8 mmo 1 ), carbonic acid (ll.lg, 34.2mmol) The mixture was stirred at 60 ° C for 2 hours, and then allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride and brine and dried over anhydrous magnesium sulfate After the organic layer was filtered and concentrated, the obtained residue was purified by silica gel column chromatography (hexane solvent: ethyl acetate = 1 〇: 1) to give 2-[( 5-bromopyrimidin-2-yl) Oxy]-2-methylpropionic acid ethyl vinegar (217 · 9 mg) MS ( ESI ) : 2 8 9 ( M + l ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.15 ( t, J = 7.2 Hz, 3H) 1.71 ( s, 6H) 4.15 ( q, J = 7.2 Hz, 2H ) 8.49 ( s, 2H ) (2) in 2-[(5-bromopyrimidin-2-yl)oxy]-2-yl Ethyl propyl propionate (214.7 mg, 0.743 mmol), 4-nitrophenylboronic acid (130.2 mg '0.780 mmol), acetic acid mesh (16.7 mg, 0.074 mmol), triphenylphosphine (58.5 mg '0.223 mmol) In a solution of dioxane (4.3 ml), 2 M aqueous sodium carbonate solution was added at room temperature ( 1. 9 ml, 3.72 mmol), and the mixture was stirred at 80 ° C for 1 hour under a nitrogen atmosphere. After cooling to room temperature, the reaction mixture was diluted with chloroform. The organic layer was washed with water and dried over anhydrous magnesium sulfate. Filtration and concentration 'The residue obtained was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 10:1) to give 2-methyl-2-{[ 5-(4-nitrobenzene) Ethylpyrimidin-2-yloxy}propionic acid ethyl ester (245.8 mg MS (ESI): 332 (M + l) -133 - 200918053 1H NMR (3 00 MHz, CDC13) δ ppm 1.18 (t, J = 7.2

Hz, 3H) 1.77 ( s, 6H) 4.18 ( q, J = 7.2 Hz, 2H ) 7.69 ( d, J=8.7 Hz, 2H) 8.35 ( d, J-8.7 Hz, 2H) 8.75 ( s, 2H ) ( 3) In a solution of ethyl 2-methyl- 2-{[5-(4-nitrophenyl)pyrimidin-2-yl]oxy}propanoate (245.0 mg, 0.73 9 mmol) in methanol (7.4 ml) 2% platinum carbon (73.5 mg) was added, and the mixture was stirred at room temperature for 1 day under a hydrogen atmosphere, and the solid matter was removed by filtration through a fluorite, and the filtrate was concentrated, and the resulting solid was suspended in isopropyl ether and filtered. The title was obtained as 2-ethyl [5-(4-aminophenyl)pyrimidin-2-yl]oxy}-2-methylpropanoic acid ethyl ester (95.5 mg). MS ( ESI ) : 3 02 ( M+l ) 1H NMR (3 00 MHz, CDC13) δ ppm 1.14 ( t, J = 7.2

Hz, 3H ) 1.74 ( s, 6H) 3.70-3.90 ( br, 1H) 4.16 ( q, J = 7.2

Hz,2H) 6.77 ( d, J = 8.4 Hz, 2H ) 7.3 0 ( d, J=8.4 Hz, 2H ) 8.60 ( s, 2H ) (4 ) in 2- {[ 5- (4-aminophenyl) To a solution of pyrimidine-2-yloxy]-2-methylpropanoic acid ethyl ester (84.4 mg, 〇.281 mmol) in tetrahydrofuran (1 ml), 2-methoxy-5-methylphenylisocyanate ( 〇.〇826ml '0.563mmol), stirred at room temperature for 2 days (adding 0.025ml of 2-methoxy-5-methylphenylisocyanate in the middle), the reaction solution was diluted with ethyl acetate, and the organic layer was Washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The obtained residue was chromatographed on a silica gel column (developing solvent; hexane: ethyl acetate = 2: 1 to 1 · · 1] Purification 'obtained 2-{[5-(4-{[(2-methoxy-5-methylphenyl)amino-134-200918053-mercapto]amino}phenyl)pyrimidine-2 - Ethyloxy-2-ethylpropanoate (80.7 mg). (Example 1 6) According to the production method of Example 15, 2-methylphenyl isocyanate and 2-chlorophenyl isocyanate were used instead of 2-methoxy-5-methylphenyl isocyanate to obtain the following Inventive compound. 2-{[5_(4_丨[(2-ethylphenyl)aminocarbamoyl]amino}phenyl)pyrimidin-2-yl]oxy}-2-methylpropanoic acid ethyl ester (compound No. 19) 2· { 5_( 4_ { 〔(2-Chlorophenyl)aminomethylindolyl)amino}phenyl)pyrimidin-2-yl]oxy}-2-methylpropanoic acid ethyl ester ( Compound No. 20) (Example 1 7) 2_丨[5-(4-{[(2-Methoxy-5-methylphenyl)aminocarbamoyl]amino}phenyl)pyrimidine-2 -yl]oxy}-2-methylpropionic acid (Compound No. 21) was produced from 2-{[5-(4-{[(2-methoxy-5-methylphenyl)aminocarbinyl) a mixed solution of ethylamino}phenyl)pyrimidin-2-yloxy]-2-methylpropanoic acid ethyl ester (80.7 mg, 0.17 4 mmol) in tetrahydrofuran (2 ml) and methanol (1 ml), 6 Μ The sodium hydroxide aqueous solution (0.5 ml) was stirred at room temperature for 3 hours, and the reaction mixture was neutralized with a 1N aqueous solution of hydrochloric acid, and diluted with ethyl acetate. The organic layer was washed with brine, and the organic layer was dried. Drying with magnesium sulfate, filtration, concentration, and the resulting solid of -135-200918053 was suspended in ethyl acetate/isopropyl ether. The solid was filtered to give 2-{[5-(4-{[(2-methoxy-5-methylphenyl)aminocarbamoyl]amino}phenyl)pyrimidin-2- as a colorless solid. Oxy] -2-methylpropionic acid (3 18 mg). (Example 1 8) According to the production method of Example 17, by using 2-{[5-(4-{[(2-ethylphenyl)aminocarbamoyl]amino}phenyl)pyrimidine- 2-yl]oxy}-2-methylpropionic acid ethyl ester, 2-{[5-(4-{[(2-chlorophenyl)aminocarbamimidino)aminopurinylphenyl)pyrimidine-2 -ethyl]oxy}-2-methylpropionic acid ethyl ester, substituted 2-{[5-(4-{[(2-methoxy-5-methylphenyl)aminomethylindenyl)amine Ethylphenyl)pyrimidin-2-yl]oxy}-2-methylpropionic acid ethyl ester gave the following compounds of the invention. 2-{ 〔5-(4-{ 〔(2-ethylphenyl)aminocarbamoyl)amino}phenyl)pyrimidin-2-yl]oxy}-2-methylpropanoic acid (Compound No. 22 2-{ 〔 5-(4-{[(2-Chlorophenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]oxy}-2-methylpropanoic acid (Compound No. 23) (Example 1 9 ) 2- { [ 5- ( 4- { 〔 (2,3 -Dimethoxyphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]oxy} Ethyl 2-methylpropionate (Compound No. 24) was prepared from 2-{[ 5-(4-aminophenyl)pyrimidin-2-yl]oxy}-2-methylpropanoate (154 mg, 0.51 1 mmol) in chloroform (3 ml) solution -136-200918053, pyridine (〇.〇 62ml, 0.76 7mmol), and 4-nitrophenyl chloroformate (123.6mg, hydrazine) were added under ice cooling. .613 mmol), stirred at room temperature for 1 hour. Add triethylamine (0.107 ml, 0.767 mmol) and 2,3-dimethoxyaniline (〇.〇 824 ml, 0.613 mmol) to the reaction mixture. After stirring for 15 hours, the reaction solution was diluted with ethyl acetate, and the organic layer was saturated with saturated aqueous ammonium chloride and saturated aqueous sodium hydrogen carbonate. The organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified with EtOAc EtOAc EtOAc EtOAc (4-{ 〔(2,3-Dimethoxyphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]oxy}-2-methylpropionic acid ethyl vinegar (155.6mg ). (Example 20) 2-{[5-(4-{[(2,3-Dimethoxyphenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]oxy} -2 -Methylpropionic acid (Compound No. 25) was produced from 2-{[5-(4-{[(2,3-dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyrimidine- Add a 6M aqueous solution of sodium hydroxide (0.5 ml) to a mixed solution of ethyl 2-yloxy]-2-methylpropanoate (97.3 mg, 175.175 mmol) in tetrahydrofuran (2 ml) and methanol (1 ml). After stirring at room temperature for 1 hour, the reaction mixture was neutralized with a 1N aqueous solution of hydrochloric acid, diluted with ethyl acetate, and the organic layer was washed with saturated brine and water, and then the organic layer was concentrated to yield solids. Suspended in ethyl acetate and filtered off solids to give 2-{[4-(4-{[[2,3-di-137-200918053 methoxyphenyl)aminomethylindolyl]amine as a colorless solid Phenylphenyl)pyrimidin-2-yl]oxy}-2-methylpropanoic acid (64.6 mg). (Example 21) 4-{[5-(4-{[(2-methoxy-5-methylphenyl)aminocarbamoyl]amino}phenyl)pyrimidin-2-yl]oxanium Preparation of 2-methyl 2,2-dimethylbutanoic acid (Compound No. 26) (5 ml of 5-bromo-2-hydroxypyrimidine (10 mg, 0.572 mmol) of dimethylformamide (1 ml) To the solution, methyl 4-bromo-2,2-dimethylbutanoate (Ref. Tetrahedron 2004, 50, 32, 9 8 2 5 - 98 3 0 ) (150 mg, 0.717 mmol), Carbonic acid (186 mg, 0.572 mmol), stirred at 100 ° C for 1 hour, allowed to cool to room temperature, then the reaction mixture was diluted with ethyl acetate, and the organic layer was washed with saturated aqueous ammonium chloride and brine. After washing, the organic layer was dried over anhydrous magnesium sulfate, and then filtered and evaporated, and the obtained residue was purified by hexane column chromatography (hexane: ethyl acetate = 9:1) to give 4-[( 5-bromopyrimidin-2-yl)oxy]-2,2-dimethylbutanoic acid methyl ester (76_7 mg). MS (ESI): 3 03 (M+l) 1H NMR (3 00 MHz, CDC13) 5 ppm 1 .27 ( s, 6H ) 2.09 ( t, J = 6.9 Hz, 2H) 3.69 ( s, 3H) 4.38 ( t, J = 6.9 Hz, 2 H) 8.5 1 ( s, 2H ) (2 ) 4-[( 5-Bromopyrimidin-2-yl)oxy]-2,2-dimethylbutanoic acid methyl vinegar (76.7 mg, 0.253 mmol), 4-Nitro-based decanoic acid (42.8 mg, 0.266 mmol), acetic acid (5.7 mg, 〇. 〇 25 mmol), -138-200918053 triphenylphosphine (1 9.9 mg, 0.076 mmol) of dioxane (2 ml) 2M sodium carbonate aqueous solution (0.633 ml, 1.27 mmol) was added to the solution at room temperature. The mixture was stirred at 80 ° C for 1 hour under a nitrogen atmosphere. After allowing to cool to room temperature, the reaction mixture was diluted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated, and the obtained residue was chromatographed on a silica gel column (developing solvent; hexane: ethyl acetate = 4:1 to 2: 1] Purification to obtain 2,2-dimethyl-4-{[5-(4-nitrophenyl)pyrimidin-2-yl]oxy}butanoic acid methyl ester (73.6 mg). MS (ESI) : 3 68 ( M+ 1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.3 1 ( s, 6H ) 2.15 ( t, J = 6.9 Hz, 2H) 3.72 ( s, 3H) 4.50 ( t, J = 6.9 Hz , 2H) 7.70 ( d, J = 9.2 Hz, 2H ) 8.36 ( d, J = 9.2 Hz, 2H ) 8.77 (s, 2H) (3) 2,2- 2% uranium carbon in a solution of methyl 4-{[5-(4-nitrophenyl)pyrimidin-2-yl]oxy}butanoic acid methyl ester (73.6 mg, 0-213 mmol) in methanol (2 ml) (15 mg), stirred at 45 ° C for 2 hours under a hydrogen atmosphere, and allowed to cool to room temperature, and then the solid matter was removed by filtration through fluorite, and the filtrate was concentrated to obtain 4 - {[ 5 - ( 4 -aminobenzene) Methyl pyrimidine-2-yloxy}-2,2-dimethylbutanoic acid methyl ester (64.2 mg). MS (ESI): 3 1 6 (M+ 1 ) 1H NMR (3 00 MHz, CDC13) δ ppm 1.29 ( s, 6H) 2.12 (t, J = 7.2 Hz, 2H) 3.70 ( s, 3H) 3.75-3.85 ( Br, 2H) 4.42 ( t, J = 7.2 Hz, 2H) 6.78 ( d, J = 8.6 Hz, 2H) 7.31 ( d, J = 8.6 Hz, 2H ) 8.63 ( s, 2H ) -139 - 200918053 (4 ) Chloroform (lml) of 4-{[ 5-(4-aminophenyl)pyrimidin-2-yl]oxy}-2,2-dimethylbutanoic acid methyl ester (64.21^, 0.204111111〇1) In the solution, pyridine (0.0247 ml, 0.35 5 mmol) and 4-nitrophenyl chloroformate (49.2 mg, 0.244 mmol) were added under ice-cooling, and the mixture was stirred at room temperature for 1 hour, and three were added to the reaction mixture. Ethylamine (0.0426 ml, 0.305 mmol), and 2-methoxy-5-methylaniline (33.5 mg '0.244 mmol) were stirred at room temperature for 3 days, and the reaction mixture was diluted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of ammonium chloride, a saturated aqueous solution of sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. The organic layer was filtered and concentrated, and the residue obtained was chromatographed with Solvent; hexane: ethyl acetate = 1 : 1] purified to give 4-{ 〔5-(4-{ 〔 (2-methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yloxy}-2,2-dimethylbutanoic acid methyl ester (8 3.2 ra g ). (Example 22) 4-{[5-(4-{[(2-methoxy-5-methylphenyl)aminocarbamimidyl]amino}phenyl)pyrimidin-2-yl]oxanium -2,2-Dimethylbutanoic acid (Compound No. 27) was produced from 4-{[5-(4-{[(2-methoxy-5-methylphenyl)aminocarbamyl] a mixed solution of aminoethyl}phenyl)pyrimidin-2-yloxy}-2,2-dimethylbutanoic acid methyl ester (83.2 mg, 0.174 mmol) in tetrahydrofuran (2 ml) and methanol (1 m 1 ) Into the mixture, dilute 6 NaOH aqueous solution (1 m 1 ), stir at room temperature for 15 hours, add 1 Μ hydrochloric acid aqueous solution to the reaction solution -140-200918053 and dilute with ethyl acetate, the organic layer After washing with a saturated aqueous solution of sodium chloride, the organic layer was concentrated, and the obtained residue was purified by silica gel column chromatography (eluent solvent; ethyl acetate:methanol = 10:1). Ethyl acetate / isopropyl ether, filtered to give 4-{[5-(4-{[(2-methoxy-5-methylphenyl)aminomethylindenyl)amine as a colorless solid Phenyl)pyrimidin-2-yloxy}-2,2·dimethylbutanoic acid (52 mg (Example 23) 1-[ 5- (4- { Manufacture of (2-methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]piperidine-4-carboxylic acid methyl ester (Compound No. 28) 1) In a mixed solution of 5-bromo-2-chloropyrimidine (lg, 5.22 mmol) in dioxane (5 ml) and dimethylformamide (1 ml), methylisopiperidate (1.41 ml) was added. , 10_4mmol), stirred for 20 minutes with got, and allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate and washed with water and saturated brine. The organic layer was dried over magnesium sulfate, then filtered and concentrated. The solid matter thus formed was suspended in isopropyl ether and filtered to give 1-(5-bromoindole-2-yl)piperidin-4-indole methyl vinegar (5i7 mg). MS (ESI) : 3 00 ( M+1 ) (2) methyl 1-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate (516 mg, 1.72 mmol), 4-nitrophenylboronic acid Alcohol ester (47〇.5mg, l_89mmol), cesium acetate (38.5mg, 〇172mmol), triphenylphosphine (1 3 5 .1 mg, 0,5 1 5 mm ο 1 ) of dioxane (丨〇m 1) In solution, chamber -141 - 200918053 added 2M aqueous sodium carbonate solution (4.3ml, 8.59mmol), nitrogen The mixture was stirred at 8 Torr for 1 hour, and then allowed to cool to room temperature. The reaction mixture was diluted with chloroform. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and then filtered and concentrated to give residue. Purification by hydrazine column chromatography (developing solvent; hexane: ethyl acetate = 2:1 to 0:1) to give 1-[ 5-(4-nitrophenyl)pyrimidin-2-yl]piperidine- 4-carboxylic acid methyl ester (415.2 mg) ° MS (ESI): 343 (M+l) 1H NMR (3 00 MHz, CDC13) δ ppm 1.12-1.35 ( m, 2H ) 1.65- 1.85 ( m, 2H) 2.52-2.73 ( m, 1H) 3.06-3.25 ( m, 2H) 3.71 ( s, 3H) 4.58-4.80 ( m, 2H) 7.63 ( d, J = 8.9 Hz, 2H ) 8.30 ( d, J = 8_9 Hz, 2H ) 8.60 ( s, 2H) (3 ) Methyl 1-[ 5-(4-nitrophenyl)pyrimidin-2-yl]piperidine-4-carboxylate (205.5 mg, 0.600 mmol) 2% platinum carbon (41_1 mg) was added to the solution (4 ml), and the mixture was stirred at 45 ° C for 4 hours under a hydrogen atmosphere. After cooling to room temperature, the solid matter was removed by filtration through fluorite, and the filtrate was concentrated to obtain 1 -[5-(4-Aminophenyl)pyrimidin-2-yl]piperidine-4-carboxylic acid methyl ester (144.1 mg). MS ( ESI ) : 3 1 3 ( M+l ) (4 ) 1-[5-(4-Aminophenyl)pyrimidin-2-yl]piperidine-4-carboxylic acid methyl vinegar (143 mg, 0.458) To a solution of mmol) in tetrahydrofuran (1 ml), 2-methoxy-5-methylphenylisocyanate (0.1476 ml, 1.0 mmol) was added and stirred at room temperature for 3 days (on the way, 0.100 ml of 2 was added) -Methoxy-5-methylphenylisocyanate), the reaction mixture was concentrated, and the solid formed -142-200918053 was suspended in ethyl acetate and filtered to give 1-[5-(4- {[ (2-Methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]indole D-butyl acid methyl vinegar (159 mg). (Example 24) According to the production method of Example 23, by using ethyl pipecolate, ethyl piperidate, and ethyl 4-piperidine acetate instead of methyl isopiperidate, the following was obtained. A compound of the invention. 1-[5-(4-{ 〔(2-methoxy-5-methylphenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]piperidine-2-carboxylic acid Base ester (Compound No. 29) 1-[5-(4-{[(2-Methoxy-5-methylphenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]piperidin Ethyl pyridine-3-carboxylate (Compound No. 30) {1-[5-(4-{ 〔(2-Methoxy-5-methylphenyl)aminocarbamoyl]amino}benzene Ethyl pyrimidin-2-yl]piperidin-4-yl}acetic acid ethyl ester (Compound No. 3 1 ) (Example 25) 1-[5-(4-{ 〔(2-methoxy-5-A) Benzyl)aminomethylmercapto]amino}phenyl)pyrimidin-2-yl]piperidine-4-carboxylic acid (Compound No. 32) manufactured in 1-[5-(4-{ 〔 (2- Methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]piperidine-4-carboxylic acid methyl ester (-143- 200918053 55.2 mg, 0.116 mm〇 l) a mixture of tetrahydrofuran (4 ml) and methanol (4 ml) was added to a 6 M aqueous solution of sodium hydroxide (1 m 1 ) to be stirred at room temperature for 2 hours, and neutralized with 1 Μ aqueous hydrochloric acid. Dilute the ethyl ester and use the organic layer The organic layer was washed with anhydrous magnesium sulfate, filtered and concentrated, and the solid formed was suspended in ethyl acetate, and the solid was filtered to give 1-[4-(4-{[ ( 2-Methoxy-5-methylphenyl)aminomethylindolyl]amino}phenyl) Chelate D疋-2-yl] D疋-4-decanoic acid (41.6 mg). (Example 26) According to the production method of Example 25, by using 1-[5-(4-{[(2-methoxy-5-methylphenyl)aminomethylindenyl]amino}benzene Ethyl pyrimidin-2-yl]piperidine-2-carboxylic acid ethyl ester, i-[ 5-(4-{[(2-methoxy-5-methylphenyl)aminomethylindenyl]amine Ethyl phenyl)pyrimidin-2-yl]piperidin-3-carboxylic acid ethyl ester, {i-[ 5-(4-{[(2-methoxy-5-methylphenyl))amino) Ethyl)amino}phenyl)pyrimidin-2-ylpyrimidin-2-yl]piperidin-4-yl}acetic acid ethyl ester, substituted 1 _[ 5 · ( 4 - { 〔 (2-methoxy) -5-Methylphenyl)aminomethylmercapto]amino}phenyl)pyrimidin-2-yl]piperidine-4-carboxylic acid methyl ester gave the following compound of the present invention. [(2-Methoxy-5-methylphenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]piperidine-2-carboxylic acid (Compound No. 33) [(2-A Oxy-5-methylphenyl)aminomethylmercapto]amino}phenyl)pyrimidin-2-yl]piperidine·3-carboxylic acid (compound No. 3 4 ) {1-[5-(4- {[(2-Methoxy-5-methylphenyl)aminocarbamimidyl]-144- 200918053 Amino}phenyl)pyrimidin-2-yl]piperidin-4-yl}acetic acid (Compound No. 35 (Example 2 7 ) ({ (3R) -1-[5-(4-{ 〔(2-methoxy-5-methylphenyl)aminocarbamoyl)amino}phenyl)pyrimidine Manufacture of ethyl-2-ylpyrrolidine-3-yl}oxy)acetate (Compound No. 36) (1) Dioxane in 5-bromo-2-chloropyran (536.8 mg, 2.78 mmol) (2_5ml) and dimethylformamide (〇.5ml) in a mixed solution, adding R - ( -) -3 - pyridyl alcohol (P yrr 〇1 id in 0 1 ) hydrochloride under water cooling ( 686.1 Mg, 5_55mmol) and triethylamine (0.7738ml, 5.55mmol), stirred at 80 ° C for 40 minutes, allowed to cool to room temperature, the reaction solution was diluted with ethyl acetate, the organic layer was saturated with water food The water was washed, and the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated, and the solid formed was suspended in isopropyl ether and filtered to give (3R)-1-( 5-bromopyrimidine-2) -yl)pyrrolidin-3-ol (249.2 mg). MS ( ESI ) : 244 ( M+l ) (2 ) (3R) -1- ( 5-bromopyrimidin-2-yl)pyrrolidin-3-ol (239.9 mg, 0.983 mmol), 4-nitrobenzene a solution of boronic acid (269.2mg, 1.08mmo 1 ), acetate pin (22.1mg, 0.098mmol), triphenylphosphine (77.3mg, 〇.295mmol) in dioctane (5ml), 2 室温 at room temperature Aqueous sodium carbonate solution (2 · 5 m 1 , 4.9 1 mm ο 1 ), dissipated at 8 QC for 1.5 hours under nitrogen atmosphere, and allowed to cool to room temperature. The reaction solution was diluted with chloroform, and the organic layer was treated with water. After washing, the organic layer was dried over anhydrous magnesium sulfate-145-200918053, and the organic layer was added to the organic layer, filtered, washed with chloroform, and then washed with ethyl acetate to obtain a solid (3 R). )-1 _[ 5 - ( 4 -Nitrophenyl) pyridin-2-ylpyrrolidine-3-ol ( 2 1 5.6 mg ). MS ( ESI ) : 287 ( M+l ) (3 ) (3 R ) -1 -[ 5 - ( 4 -nitrophenyl)pyrimidin-2-ylpyridin-3-ol (126.4 mg, 0.442 mmol) of dimethylformamide (2.2 ml) was added to sodium hydride under ice-cooling (Ili [I-flow paraffin 4 5 %) (39 mg, O.883 mmol) and bromoacetic acid (0.098) Ml, 0.8 8 3 mm ο 1 ), disturbed at room temperature for 4 hours (adding sodium hydride (adding paraffin wax 45%) (39mg) and ethyl bromoacetate (0_200ml)), adding water to the reaction mixture. After the mixture was diluted with ethyl acetate, the organic layer was washed with saturated aqueous ammonium chloride and brine, and the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. Ethyl ({(3R)-l-[5-(4-nitrophenyl)pyrimidin-2-yl]pyrrolidin-3-yl}oxy)acetate (47.9 mg) was obtained. MS ( ESI ) : 3 73 ( M+1 ) (4 ) in ({ ( 3 R ) - 1 -[ 5 - ( 4 -nitrophenyl)pyrimidin-2-yl]pyrrolidin-3-yl}oxy Ethyl acetate (47.9 mg, 0.129 mmol) in methanol (5 m 1 ) was added with 2% platinum carbon (1 〇 mg), stirred at room temperature for 1 hour under hydrogen atmosphere, filtered by fluorite. The solid matter was removed, and the filtrate was concentrated to give ({(3R)-b[5-(4-aminophenyl)pyrimidin-2-yl]pyrrolidin-3-yl}oxy)acetic acid ethyl ester (42.8 mg) . MS ( ESI ) : 3 43 ( M+l ) -146- 200918053 (5 )ethyl ({ ( 3R) -1-[ 5- ( 4-aminophenyl)pyrrolidin-3-yl}oxy)acetate To a solution of 42.8 mg of tetrahydrofuran (2 ml), 2-methoxycyanate (〇.〇55ml '0_3 7 5mmol) was added and stirred at room temperature to add 2-methoxy-5-methylphenyl Isocyanate (0. The reaction mixture was diluted with ethyl acetate, the organic layer was washed with tf, and the organic layer was dried over anhydrous magnesium sulfate, and the solid formed was suspended in ethyl acetate / isopropyl acid ( {( 3R )-Bu [5-(4-{ 〔(2-Methoxyaminomethylindolyl)amino}phenyl)pyrimidin-2-ylpyridinium)acetate (48-1 mg). Example 2 8) ({( 3R )-Bu [5-(4-{ 〔(2-methoxy)aminomethylindolyl)amino}phenyl)pyrimidin-2-yl]oxy)acetic acid (Compound No. 3 7) Manufactured from ({ ( 3R ) -1-[ 5- ( 4- { 〔(2-methyl)aminocarbamoyl)amino}phenyl)pyrimidin-2-yl}oxy)acetic acid ethyl 6M liquid (1 ml) was added to a mixed solution of ester (44 mg, 0-087 mmol) and methanol (4 ml), and stirred at room temperature for 2 hours. Neutralization of aqueous solution of liquid acid, by filtration ({( 3R) -1-[ 5- ( 4- { 〔(2-methyl)aminomethylmethyl) yl) phenyl) Pyrimidine-2-ylpyrimidin-2-yl, 0.125 mmol) :-5-methylphenyl isomixture for 3 days (055 ml in the middle), 3 and brine were concentrated and concentrated, and filtered. 5-methylphenyl)rrolidine-3-yl}oxy-5-methylbenylpyrrolidin-3-yl}oxy-5-methylphenyl]pyrrolidine-3-yltetrahydrofuran (1 ml of sodium hydroxide was added to water to dissolve 1 Μ salt: / to give yellow white oxy-5-methyl benzene] pyrrolidine-3-yl-147-200918053 } oxy) acetic acid (3 1 mg). (Example 2 9 ) 3- {[ 5-(4- {[(2-methoxy-5-methylphenyl)aminocarbamoyl]amino}-2-methylphenyl)pyrimidine- Manufacture of 2-yloxyoxo-2,2-dimethylpropionic acid methyl ester (Compound No. 3 8 ) (1) in 3-[(5-bromopyran-2-yl)oxy]_2,2 -Methyl dimethylpropionate (130 mg, 0.449 mmol), 2-methyl-4-nitro-benzyl benzoic acid pinacol ester (177 mg '0.674 mmol), palladium acetate (10.lmg, 〇.〇45mmol) , a solution of triphenylphosphine (35.3 mg, 〇.135 mmol) in two chews (2.5 m 1 ), adding 2 Μ aqueous sodium carbonate solution (1.12 m 1 , 2.25 mmol) at room temperature under nitrogen atmosphere Take 8 0. (: stirring for 1 hour) After cooling to room temperature, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (developing solvent; hexanes: ethyl acetate = 4:1) to give 2,2-dimethyl-3-{[ 5-(2-methyl-4-nitro) Phenyl)pyrimidin-2-yl]oxy}propionic acid methyl ester (125 mg) MS (ESI): 3 4 6 ( Μ + 1 ) 1H NMR (3 00 MHz, CDC13) δ ppm 1.38 ( s, 6H ) 2.41 ( s, 3H) 3.73 ( s, 3H) 4.47 ( s, 2H) 7.3 0-7.40 ( m, 1H) 8.10-8.25 (m, 2H) 8.51 ( s, 2H) (2) at 2,2- Dimethyl-3-{[5-(2-methyl-4-nitrophenyl)pyrimidinium]]-2-yloxy]propionic acid methyl ester (125.2 mg, 0.363 mmol) in methanol (2 ml) 2% uranium carbon (50mg) was added to the solution, and the mixture was stirred at room temperature for 1 day under hydrogen atmosphere -148-200918053. The solid matter was removed by perovskite, and the filtrate was concentrated to obtain the residue. Column chromatography [developing solvent; hexane: acetic acid ethyl acetate = 2: 1 to 1: 1] purification 'obtained 3 - { 〔 5 - ( 4 -amino-2-methyl Phenyl)pyrimidin-2-yloxy}-2,2-dimethylpropionic acid methyl ester (8 9 -9 mg) MS ( ESI ) : 3 16 ( M+l ) 1H NMR ( 3 00 MHz , CDC13) δ ppm 1.38 ( s, 6H ) 2.21 ( s, 3H) 3.72 ( s, 3H) 4.43 ( s, 2H) 6.5 6-6.8 3 ( m, 2H ) 6.92-7.0 5 ( m, 1H ) 8.45 ( s, 2H ) (3) 3-{[5-(4-Amino-2-methylphenyl)pyrimidin-2-yl]oxy}-2,2-methylpropanoic acid methyl ester (88_5111 §, 0.281111111〇1) in chloroform (2ml) solution, add pyridine (〇〇34ml, 0.421mmol), and 4-nitrophenyl chloroformate (6 2 · 2 mg, 0.3 0 9mmol) under ice cooling 'Stirring at room temperature for 1 hour, adding triethylamine (0.0587 ml, 0-421 mmol), and 2-methoxy-5-methylaniline (46.2 mg, 0.33 7 mm〇l) to the reaction mixture at room temperature After stirring for 3 hours, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of ammonium chloride, a saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried and evaporated. Purification by gel column chromatography [NH oxime, developing solvent; hexane: ethyl acetate = 2: 1 to 1 · _ 1] 3-丨[5-(4-丨[(2-methoxy-5-methylphenyl)aminomethylindolyl]amino}-2-methylphenyl)pyrimidin-2- Methyl oxo- 2,2-dimethylpropionic acid methyl ester (96.8 mg). -149- 200918053 (Example 3 0 ) 3_{ 〔5_(4_{ 〔(2-Methoxy-5-methylphenyl)aminocarbamoyl)amino}-2-methylphenyl)pyrimidine Benzyl-2-oxo}-2,2-dimethylpropanoic acid (Compound No. 3 9 ) was produced from 3_{ 〔5-(4-{ 〔(2-methoxy-5-methylphenyl) Aminomethylmercapto]amino}-2-methylphenyl)pyrimidin-2-yloxy}-2,2-dimethylpropanoic acid methyl ester (96 mg, 〇.201 mmol) in tetrahydrofuran (2 ml) To a mixed solution of methanol (1 ml), a 6-aqueous sodium hydroxide aqueous solution (5 ml) was added, and the mixture was stirred at room temperature for 6 hours, and the mixture was neutralized with aq. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated, and the obtained residue was chromatographed on a silica gel column (developing solvent; hexane: ethyl acetate = 1 : 1 Purification to give 3 - { 〔 5 - ( 4 - {[(2-methoxy-5-methylphenyl)aminocarbamoyl]amino}-2-methylphenyl)pyrimidine as a colorless solid 2-yloxy}-2,2-dimethylpropanoic acid (46.5 mg). (Example 3 1 ) [5-(4-{ 〔(2,3·Dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy} -2 - Preparation of ethyl propyl propionate (Compound No. 40) (1) In a solution of 5-distress [1疋-2 (1H)·嗣 (3.0g, 17.2mmol) in dimethylformamide (60ml) 2, bromoisobutyric acid ethyl ester (6.7g '34.5mm〇l), fc acid (11.2g, 34.5mmol), and stirred at 60 ° C for 1 · 5 hours 'after cooling to room temperature, The reaction mixture was diluted with ethyl acetate in -150-200918053, and the organic layer was washed with aqueous ammonium chloride and brine, dried over anhydrous magnesium sulfate, and then filtered and concentrated to give residue. Purification by gel column chromatography [developing solvent; hexane: ethyl acetate = 9: 1] afforded ethyl 2-[(5-bromopyridin-2-yl)oxy]-2-methylpropanoate ( 2.08g). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.15 ( t, J = 7.2 Hz, 3H) 1.65 ( s, 6H) 4.14 ( q, J = 7.2 Hz, 2H) 6.67 ( d, J = 8.4 Hz, 1H) 7.64 ( dd, J = 2.7 Hz, 8.4 Hz, 1H) 8.08 ( d, 1 = 2.1 Hz, 1 H ) (2) in 2-[(5-bromo-pyridylpyridin-2-yl)oxy]-2 -ethyl propyl propionate (2.08 g, 7.22 mmol), 4-nitrophenylboronic acid (1 · 2 2 g, 7.5 8 mmol), palladium (II) acetate (162 mg, 0.722 mmol), triphenylphosphine ( 568 mg, 2.I7 mmol) of two chewing solution (40 ml), 2M sodium carbonate aqueous solution (18 ml, 36.1 mmol) was added at room temperature, stirred at 80 ° C for 30 minutes under nitrogen atmosphere, and allowed to cool to room temperature. After that, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate, and then filtered and concentrated, and the obtained residue was chromatographed by column chromatography. Solvent; hexane: ethyl acetate = 9: 1] Purified to give ethyl 2-methyl-2-{[ 5-(4-nitrophenyl)pyridin-2-yl]oxy}propanoate (1.64 g). MS ( ESI ) : 33 1 ( M+1 ) 1H NMR ( 300 MHz, CDC 13 ) δ ppm 1.16 ( t, J = 7.2 Hz, 3H) 1.70 ( s, 6H) 4.18 ( q, J = 7.2 Hz, 2H) 6.88 ( d, J = 8.7 Hz, 1H) 7.66 ( d, J = 9.0 Hz, 2H) 7.83 ( dd, J = 2.7 -151 - 200918053

Hz, 8.7 Hz, 1H) 8.29 ( d, J = 9.0 Hz, 2H) 8.33 ( d, J = 2.7 Hz, 1 H ) (3 ) in 2-methyl-2- {[ 5- ( 4-nitro) Phenyl)pyridin-2-yl]oxy}propionic acid ethyl ester (1.64 g, 4.96 mmol) in methanol (40 ml) was added to 2% platinum carbon (300 mg) and stirred at room temperature under hydrogen atmosphere 30 After stirring for 4 hours at 45 ° C, the solid matter 'concentrated filtrate was removed by filtration with fluorite to obtain a solid 2 - methyl-2 - { [ 5 - ( 4 - aminophenyl) pyridine - 2 -yloxy}propionic acid ethyl ester (1.39 g). MS ( ESI ) : 3 01 ( Μ + 1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.14 ( t, J = 7.1 Hz, 3H) 1.69 ( s, 6H) 3.64-3.82 ( br, 2H ) 4.15 ( q, J-7.1 Hz, 2H ) 6.69-6.83 ( m, 3H ) 7.27-7.3 6 ( m, 2H ) 7.67-7.77 (m, 1 H ) 8. 1 6-8.24 ( m, 1H ) (4 ) 2-methyl-2-{[ 5-(4-aminophenyl)pyridin-2-yl]oxy}propionic acid ethyl ester (199 mg, 0.663 mmol) in chloroform (4 ml) Pyridine (0 · 0 8 1 m 1 , 0.9 9 5 mm ο 1 ), and 4-nitrophenyl chloroformate (160 mg, 0.796 mmol), stirred at 0 ° C for 1 hour, and added to the reaction mixture Ethylamine (0 · 1 3 9 m 1 ' 0 · 9 9 5 mm ο 1 ), and 2,3-dimethoxyaniline (〇.l〇7ml, 〇.796mmol), stirred at room temperature 1 5 The reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. The solid was filtered, and the filtrate was concentrated. The obtained solid was suspended in ethyl acetate / diisopropyl ether and filtered to give colorless. Solid 2-{[ 5-(4- -152 - 200918053 { 〔(2,3-Dimethoxyphenyl)aminomethylindolyl)aminophenyl)pyridin-2-yl]oxy}- Ethyl 2-methylpropionate (306 mg). (Example 3 2 ) According to the production method of Example 31, by using 2-methoxy-5-methylaniline, 2-methoxy-5-trifluoromethylaniline, 2-chloro-4-fluoro Aniline, 3,5-dimethylbenzylamine, cyclohexylamine, 2,4-dimethylaniline, 3,5-dimethylaniline, 2-chloro-5-methoxyaniline, 3-chloro- 2-Methylaniline, 1-adamantylamine, and 2,3-dimethoxyaniline were substituted to give the following compounds of the present invention. 2-{[5-(4-{ 〔(2-methoxy-5-methylphenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}-2-methyl Ethyl propionate (Compound No. 4 1 ) 2-( {5-[4-( { [2-methoxy-5-(trifluoromethyl)phenyl]aminomethylindenyl)amino)benzene Ethyl pyridin-2-yl}oxy)-2-methylpropionic acid ethyl ester (Compound No. 4 2 ) 2-{ 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)amino Methylamino]amino}phenyl)pyridin-2-yl]oxy}-2-methylpropionic acid ethyl ester (Compound No. 43) 2- { [5-(4-{[(3,5-II) Methylbenzyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}-2-methylpropionic acid ethyl ester (Compound No. 44) 2-[ ( 5- { 4-[ Ethyl (cyclohexylaminomercapto)amino]phenyl}pyridine-2-yloxy]-2-methylpropanoate (Compound No. 45) 2-{[5-(4-{[( 2,4-Dimethylphenyl)aminomethylindenyl]amino-153- 200918053 }Phenyl)pyridin-2-yl]oxy}-2-methylpropionic acid ethyl ester (Compound No. 46) 2 -{[5-(4-{[(3,5-dimethylphenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}-2- Ethyl propionate (Compound No. 47) 2-{ 〔5-(4-{[(2-Chloro-5-methoxyphenyl)aminocarbamoyl]amino}phenyl)pyridine-2- Ethyl}oxy-2-ethylpropionate ethyl ester (Compound No. 4 8 ) 2-{ 〔5-(4-{ 〔(3-Chloro-2-methylphenyl)aminomethylindenyl)amine Ethyl phenyl)pyridin-2-yloxy]-2-methylpropanoic acid ethyl ester (Compound No. 49) 2-[ ( 5- { 4-[(Adamantyl-1-ylaminomethyl) Ethyl]phenyl}pyridin-2-yl)oxy]-2-methylpropionic acid ethyl ester (Compound No. 50) (Example 3 3) 2- { [ 5- ( 4- { 〔 ( 2, 3-Dimethoxyphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}-2-methylpropionic acid (Compound No. 51) Manufactured on 2-{[5- (4-{[(2,3-Dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyridine-2-yl]oxan-2-methylpropanoic acid ethyl ester (257 mg, To a mixed solution of tetrahydrofuran (4 ml) and methanol (2 ml), a 6 Μ aqueous sodium hydroxide solution (1 m 1 ) was added, and stirred at room temperature for 1 hour, and 1 Μ hydrochloric acid was added to the reaction mixture. Neutralize, dilute with ethyl acetate, The organic layer was washed with saturated brine, and then the organic layer was dried with <RTI ID=0.0>&&&&&&&&&&&&&&&& To give a colorless solid of 2-{[5-(4-{[(2,3-)-methoxyphenyl)aminomethyl]amino}phenyl)pyridin-2-yl]oxy} 2-methylpropionic acid (223 rng). (Example 34) According to the production method of Example 3, the following compound of the present invention 〇2-ί[5-(4-{ 〔(2-methoxy-5-methylphenyl)amine-based A was obtained.醯 〕 〕 〕 〕 〕 〕 〕 〕 〕 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物(trifluoromethyl)phenyl]aminomethylmercapto} g) base] π ratio π-but-2-yl}oxy)-2-methylpropionic acid (compound number 5 3 ) 2-{ 〔 5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl]amino}phenyl)- -2-yloxy] _2-methylpropanoic acid (Compound No. 54) 5_(4_{ 〔(3,5-Dimethylbenzyl)aminomethane]amino}phenyl)pyridin-2-yl]oxy} ·2-methylpropionic acid (Compound No. 55) 2- [(5-{4-[(Cyclohexylaminocarbamimidyl)amino]phenylpyridin-2-yl)oxy]-2.methylpropionic acid (Compound No. 56) 2_ { 〔 5_ ( 4_ { [( 2,4·Dimethylphenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy} _2_methylpropionic acid (Compound No. 57) 2_丨[5_ ( 4 -丨[(3,5-Dimethylphenyl)aminocarboxamido]amine }Phenyl)pyridin-2-yl]oxy} _2_methylpropionic acid (Compound No. 58) -155- 200918053 2-{ [5-(4-{ 〔(2-Chloro-5-methoxyphenyl) Aminomethylmercapto]amino}phenyl)pyran-2-yloxy}-2-methylpropionic acid (compound No. 59) 2-{ [5-(4-丨[(3-chloro-) 2-methylphenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yloxy}-2-methylpropanoic acid (Compound No. 60) 2 -[( 5 - Μ -[( Adamantane-1 -ylaminomethylmercapto)amino]phenyl}pyridin-2-yl)oxy]-2-methylpropionic acid (Compound No. 61) (Example 3 5) 2-{ [5- (4-{[2-Chlorophenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}-2-methylpropionic acid ethyl ester (Compound No. 62) To a solution of 2-methyl-2-{[5-(4-aminophenyl)pyridine-2-yloxy}propionic acid ethyl ester (196 mg, 〇 '652mmo1) in tetrahydrofuran (2 ml), 2 - Gas-based aliquot 63⁄4 vinegar (0.094 ml, 〇.78 mmol), stirred at room temperature for 15 hours. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated brine and Magnesium Drying, Filtration, Concentration' The solid obtained was suspended in ethyl acetate/diisopropyl ether, and filtered to give 2-{[[5_(4_{[(2-chlorophenyl))amino group as a colorless solid. Methylamino]amino}phenyl)pyridin-2-yloxyoxan-2-ethylpropionic acid ethyl ester (266 mg). (Example 3 6) According to the production method of Example 35, the following compound of the present invention was obtained by substituting 2-ethylphenylisocyanide-156-200918053 acid ester for 2-chlorophenyl isocyanate. 2-{[5-(4-{[(2-ethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxan-2-methylpropanoate ethyl ester ( Compound No. 63 (Example 3 7 ) 2-{ 〔5-(4-{ 〔(2-Phenylphenyl)aminoglycanyl)amino}phenyl)pyridin-2-yl]oxy} -2- Methylpropionic acid (Compound No. 64) was produced from 2-{[5-(4-{[(2-chlorophenyl)aminocarbamoyl]amino}phenyl)B)-steep-2-yl] To a mixed solution of tetrahydrofuran (4 ml) and methanol (2 ml) of oxy-2-ethylpropanoic acid ethyl acetoacetate (263 mg, 0.578 mmol), a 6M aqueous solution of sodium hydroxide (1 ml) was added. The reaction mixture was neutralized with 1 mL of hydrochloric acid and diluted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, filtered and concentrated to yield solids. The suspension was suspended in ethyl acetate/diisopropyl ether, and the solid was filtered to give 2-{[[4-(4-{[(2-chlorophenyl)aminomethylmethyl]amino}benzene as a colorless solid. Pyridin-2-yl]oxy}-2-methylpropionic acid (2l6 mg). (Example 3 8) In the production methods of Examples 35 and 37, the following compounds of the present invention were obtained by substituting 2-chlorophenyl isocyanate for 2-chlorophenyl isocyanate. 2-丨[5-(4-{ 〔 (2 - Ethylphenyl)aminomethylindenyl]amino}benzene-157- 200918053 yl pyridin-2-yloxy}-2-methylpropanoic acid (Compound No. 65) (Example 3 9) 3-{ [5-(4-{[(2,3-Dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyridine-2-yl]amino} -2,2-dimethylpropane Production of acid (Compound No. 6 6 ) (1) In a solution of 5-bromopyridin-2-amine (974 mg, 5-63 mmol) in dimethylformamide (2 〇ml), 2,2-dimethyl- 3_Benzyl oxopropionate (synthesized according to the literature: Org. Lett. 2003, 5, 14, 2473-2475) (2.32 g, ll_3 mmol) 'Addition of trifluoroacetic acid (7.7 g, 67.6 mmol) under ice cooling And sodium triethyl sulfonium borohydride (4 · 7 7 g, 22.5mmoI), stirred at room temperature for 1 hour, adding a saturated aqueous solution of ammonium chloride to the reaction mixture under ice-cooling Dilute and wash the organic layer with an aqueous solution of ammonium chloride and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, evaporated, evaporated, evaporated, 2-Benzylamino]benzyl-2,2-dimethylpropanoate (1.26 g). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.27 ( s, 6H ) 3.40-3.56 ( m, 2H ) 4.69-4.90 ( m, 1H) 5.13 ( s, 2H )

6.16-6.29 ( m, 1H) 7.18-7.45 ( m, 6H ) 8.00-8.11 ( m, 1H ) (2 ) in 3-[( 5-bromopyridin-2-yl)amino]-2,2-di Benzyl methacrylate (1.26 g, 3.48 mmol), 4-nitrophenylboronic acid (588 mg -158-200918053 ' 3.65 mmol), palladium (II) acetate (78.1 mg, 0.348 mmol), triphenylphosphine (274 mg, 1.04 mmol) of diterpene solution (20 ml), 2M sodium carbonate aqueous solution (8.7 ml, 17.4 mmol) was added at room temperature, and stirred at 80 ° C for 1 hour under nitrogen atmosphere, and allowed to cool to room temperature. After that, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated, and the obtained residue was chromatographed with a column. Solvent; hexane: ethyl acetate = 4: 1 to 2: 1] purified to give 2,2-dimethyl-3-{[5-(4-nitrophenyl)pyridin-2-yl]amino }Benzyl propionate (8 79 mg). (3) Ethanol (20ml) in 2,2-dimethyl-3-{[5-(4-nitrophenyl)pyridin-2-yl]amino}propionic acid vinegar (879mg, 2.17mmol) In the solution, water (2 ml), iron powder (1-21 g, 21.7 mmol), concentrated hydrochloric acid (0.1 ml) were added, and the mixture was stirred at 80 ° C for 1 hour, and the reaction solution was allowed to cool to room temperature, and then treated with fluorite. The solid matter was removed, and the filtrate was concentrated, and the obtained residue was diluted with ethyl acetate and sodium hydrogen carbonate aqueous solution, and the organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. After the organic layer was filtered and concentrated, the obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3:1 to 1:1) to give 3-{[ 5- ( 4- Aminophenyl)pyridin-2-yl]amino}-2,2-dimethylpropanoic acid benzyl ester (660 mg).

1H NMR (3 00 MHz, CDC13) δ ppm 1.31 ( s,6H ) 3.50-3.61 ( m, 2H) 3.61-3.82 ( br, 2H) 4.5 9-4.8 3 ( m5 iH )5.14 ( s, 2H) 6.32- 6.43 ( m, 1H) 6.69-6.81 ( m, 2H) 7.22-7.41 ( m, 7H ) 7.50-7.60 ( m, 1H) 8.20- 8.40 ( m > iH -159- 200918053 1 M [ 5- ( 4-amine Phenylpyridin-2-yl]amino}- 2,2--methylpropionate (149 mg, 0.396 mmol) in chloroform (3 ml) was added to the pyridine (0.04 8 ml, 0.59) under ice cooling. Methyl), and 4-nitro-based chloroformate (95 8ing, 〇475mmo丨), stirred at room temperature for 1 hour', adding triethylamine (〇.〇83ml, 0.59mmol) to the reaction solution, and 2,3-Dimethoxyaniline (〇. 〇6 4 m 1 , Ο . 4 8 mm ο 1 )' was stirred at room temperature for one night, and the reaction mixture was diluted with ethyl acetate. After washing with an aqueous solution of ammonium chloride, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, the organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated, and chromatographic column chromatography [ NH </ br> : 1] Purification, get 3- { 〔 5- ( 4- { 〔 ( 2, 3- 2 Methoxyphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]amino} -2,2-dimethylpropanoic acid benzyl ester (157 mg). MS (ESI): 5 55 ( M+1 ), 553 (M-1) (5) on 3-{ 〔5-(4-{ 〔(2,3-dimethoxyphenyl)aminomethylindenyl)amino}benzene a mixture of tetrahydrofuran (4 ml) and methanol (2 m 1 ) in a mixture of 2,2-dimethylpropionic acid benzyl ester (156 mg, 〇.281 mmol), 6 ΜAqueous sodium hydroxide solution (1 ml), disturbed at room temperature for 6 hours. 'The mixture was neutralized with 1 Μ hydrochloric acid, diluted with ethyl acetate. The organic layer was washed with water and concentrated to solidify. Suspended in ethyl acetate and filtered to give a pale yellow solid of 3_{[5_(4-{[(2,3-dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyridine -2 -yl]amino hydrazine 2 2,2- dimethylpropionic acid (1 0 1 Hi g -160- 200918053 (Example 40) According to the production method of Example 39, by using 2-methoxyl -5-methylaniline, 2,4-dimethylaniline substituted 2,3-dimethoxyaniline, using benzyl hydrazinyl cyclopropanecarboxylate (according to literature :〇rg. Lett. 2003, 5, 14, 2473 -2475 synthesis), 4_methylmercaptotetrahydro-2H_pyran-4-ylcarboxylic acid benzyl ester (according to the literature _ Org. Lett. 2003, 5, 14, 2473-2475 Synthesis) Substituting benzyl 2,2-dimethyl-3-oxopropanoate to give the following compounds of the invention. [5-(4-{ 〔(2-methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]amino} _2,2-dimethyl Propionic acid (Compound No. 6 7 ) 1_( { 〔5_(4_{ 〔(2,4-dimethylphenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]amine Cyclopropanecarboxylic acid (Compound No. 6 8 ) 4-( { [ 5-(4-{[(yl}}yl) 卩it D疋-2-yl]amino} acid (Compound No. 69) 2, 4- dimethylphenyl)aminocarbamimidylamine amine}methyl)tetrahydro-2H-pyran-4 -竣3_{ [5_(4_{ 〔 (2'4' dimethylphenyl) Aminomethylamino]amino}phenyl)

No. 70) (Example 41) -161 - 200918053 3-{[5-(4-{[(2-Chlorophenyl)aminocarbamimidyl]amino}phenyl)pyridin-2-yl]amino Manufacture of - 2,2-dimethylpropionic acid (Compound No. 7 1 ) (1 ) in 3-{[4-(4-aminophenyl)pyridin-2-yl]amino}- 2,2 2-Chlorophenylisocyanate (0.04 9 ml, 0.40 mmol) was added to a solution of benzyl dimethylpropionate (127 mg, 0.337 mmol) in tetrahydrofuran (1.5 ml), and stirred at room temperature for 3 hr. Ethyl acetate was diluted, and the organic layer was washed with a saturated aqueous solution of brine and the organic layer was concentrated, and the obtained residue was chromatographed on a silica gel column (developing solvent; hexane: ethyl acetate = 3:1 to 1:1) Purification to give 3-{[5-(4-{[(2-chlorophenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]amino}-2,2-dimethyl Benzyl propionate (173 mg). MS (ESI): 5 29 (M+1), 5 27 (M-1) (2) ??? 3-{[5-(4-{[(2-chlorophenyl)aminomethylmethyl) a mixed solution of phenyl)pyridin-2-yl]amino}-2,2-dimethylpropanoic acid benzyl ester (167 mg, 0-316 mmol) in tetrahydrofuran (2 ml) and methanol (1 ml). 6M sodium hydroxide aqueous solution (1 ml) was added, and the mixture was stirred at room temperature for 16 hours, and the mixture was neutralized with 1 Μ hydrochloric acid, diluted with ethyl acetate, and the organic layer was washed with saturated brine and water and concentrated. The solid formed was suspended in ethyl acetate/isopropyl ether, and the solid was filtered to give 3-{[4-(4-(2-chlorophenyl)aminocarbazide as a pale yellow solid. Amino]phenyl}pyridin-2-yl]amino}-2,2-dimethylpropanoic acid (134 mg). -162-200918053 (Example 42) According to the manufacturing method of Example 39 and Example 4, by using methicone cyanoic acid decyl methacrylate, 4-methyl aryl tetrahydro-2H- sulphur Substituting benzylic acid benzyl ester for benzyl 2,2-dimethyl-3- oxopropionate gave the following compounds of the invention. 1-( { 〔 5-(4-{ 〔(2-Chlorophenyl)aminomethyl hydrazinyl) fluorenyl phenyl) D-formyl-2-yl]amino} A/a a / ^ a dense / 1,4-propane propylene carboxylic acid (Compound No. 72) 4_ ( { 〔 5_ ( 4_ { 〔(2-Chlorophenyl)aminomethyl hydrazinyl) phenyl) pyridin-2-yl]amino} Tetrahydro-2H-pyran-4-carboxylic acid (Compound No. 73) (Example 43) 3_{[5-(4-{ 〔(2-methoxy-5-methylphenyl)amino group Manufacture of (1) to 2,5-bromoindole ratio B Add m-chloroperbenzoic acid (30.2 g, 114 mmol) to a solution of chloroform (81 ml) (9.0 g, 38 mmol), stir at room temperature for 15 hours, and add 1 〇% thiosulfuric acid to the reaction solution under ice cooling. The aqueous solution of sodium is extracted, and the chloroform layer is extracted, washed with 1 NaOH aqueous solution of sodium hydroxide and saturated brine, dried (anhydrous magnesium sulfate), filtered, and concentrated, and the residue obtained is chromatographed by a gel column. Chop the gum, develop the solvent; 'hexane: ethyl acetate = 2: 1> purified 'to obtain a colorless powder 2,5-dibromopyridine 1 -oxide (6 · 2 9 g ). -163- 200918053 MS ( ESI/APCI Dual ) : 252 ( M+l ) 1H NMR ( 200 MHz, CDC13) δ ppm 7.19-7.28 ( m, 1 H) 7.49-7.56 ( m, 1 H) 8.49-8.5 3 ( m, 1 H) (2) In a solution of 2,5-dibromoindole ratio steep 1-oxide (900 mg, 3_56 mmol) in toluene (18 ml), 3-hydroxy-2,2-dimethylpropanoic acid was added. Methyl vinegar (941 mg, 7.12 mmol) and potassium carbonate (984 mg, 7.12 mmol) were heated and refluxed for 18 hours, and the reaction liquid was filtered and concentrated with fluorite, and the obtained residue was chromatographed with a silica gel column. [Expansion solvent; methanol: ethyl acetate = 0: 1 to 1: 50] was purified to give 3-[(5-bromo-1-oxide pyridin-2-yl)oxy]-2,2-di. Methyl methacrylate (545 mg). MS ( ESI/APCI Dual ) : 304 ( M+l ) , 302 ( Μ - 1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1 .36 ( s, 6 H ) 3.70 ( s, 3 H) 4.31 ( s, 2 H) 6.83 ( d, J=8.9 Hz, 1 H) 7.29-7.34 (m, 1 H) 8.33-8.35 (m, 1 H) (3) in 3-[( 5-bromo-1-oxidation) Add a saturated aqueous solution of ammonium chloride (1.3 ml), indium, to a solution of methyl pyridin-2-yl)oxy]-2,2-dimethylpropanoate (200 mg, 0.658 mmol) in ethanol (1.9 ml). (90.7 mg, 0.79 mmol), heating under reflux for 1 hour, adding water to the reaction mixture, extracting with ethyl acetate, drying (anhydrous magnesium sulfate), filtering, and concentrating, using the obtained residue Purification by column chromatography (developing solvent; chloroform:methanol = 20:1 to 1 : 1 : 1) to give 3 ([5-bromopyridin-2-yl)oxy]-2,2-dimethyl Methyl propionate (115mg) -164- 200918053 MS ( ESI/APCI Dual ) : 288 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.30 ( s, 6 H) 3.69 ( s, 3 H) 4.29 ( s, 2 H ) 6.63 -6.68 ( m, 1 H) 7.60-7.66 ( m, 1 H ) 8. 1 5-8. 1 9 ( m,1 H ) (4) at 3-[ ( 5-bromopyridin-2-yl)oxy]-2,2-di Methyl propionate (140 mg, 0.486 mmol), 4-nitrophenylboronic acid (93.3 mg '0.559 mmol), triphenylphosphine (38.2 mg, 0.146 mm 〇l) of dioxane (1.94 ml) And 2M sodium carbonate aqueous solution (1.21ml) suspension was added with acetic acid (II) (10. 9mg, 0.0486mmol), and the external temperature was stirred at 80C for 45 minutes. The reaction solution was filtered and added to the filtrate. Water, extracted with ethyl acetate, dried (MgSO4), filtered and evaporated. Purification gave a yellow powder of 2,2-dimethyl-3-{[5-(4-nitrophenyl)pyridin-2-yl]oxy}propanoic acid methyl ester (130 mg). MS ( ESI/APCI Dual ) : 331 ( M+l) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.34 ( s, 6 H) 3.71 (s, 3 H) 4.40 (s, 2 H) 6.83-6.91 ( m, 1 H) 7.64- 7.72 (m, 2 H) 7.79-7.87 (m, 1 H) 8.27-8.35 (m, 2 H) 8.3 9-8.45 ( m, 1 H ) (5 ) at 2,2- Methyl dimethyl-3-{[ 5-(4-nitrophenyl)pyridin-2-yl]oxy}propanoate (120 mg, 0.362 mmol) in ethanol (1.5 ml) and tetrahydrofuran (1.5 ml) In the mixed solution, 10% cobalt carbon (12 mg) was added to the mixture, and the mixture was stirred at room temperature for 15 hours under a hydrogen atmosphere, and the reaction liquid-165-200918053 was subjected to filtration of the fluorite, and the filtrate was concentrated by using the filtrate. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1:1) to give 3-{[4-(4-aminophenyl)pyridin-2-yl] Oxy} -2,2-dimethylpropionic acid methyl ester (99 mg). MS ( ESI/APCI Dual ) : 301 ( M+l) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.32 ( s, 6 H ) 3.67-3.72 ( br, 2 H) 3.69 ( s, 3 H) 4.35 ( s, 2 H) 6.72-6.79 ( m, 3 H) 7.28 -7.3 6 ( m, 2 H) 7.71 ( dd, J = 8.6, 2.5 Hz, 1 H) 8.29 ( dd, J = 2.5, 0.7 Hz, 1 H) (6) 3 - {[ 5-(4-Aminophenyl)pyridin-2-yl]oxy} _ 2,2-dimethylpropanoic acid methyl ester (1_55£, 5.16111111〇1) 4, nitrophenyl chloroformate (1.25 g, 6.19 mmol) in chloroform (25 ml), pyridine (0.5 65 ml, 6.97 mmol) was added under ice-cooling, and the mixture was stirred for 30 min. After adding water, the mixture was extracted with ethyl acetate, dried (anhydrous magnesium sulfate), filtered, and concentrated, and then recrystallized (ethyl acetate-hexane) to give a pale yellow powder of 2,2. Dimethyl-3-{[5-(4-{[(4-nitrophenoxy)carbonyl]amino}phenyl)pyridin-2-yl]oxy}propanoic acid methyl ester (2.09 g). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.33 ( s, 6 Η) 3.71 (s, 3 Η) 4.37 (s, 2 Η) 6.79-6.84 (m, 1 H) 7.09( br, 1 H) 7.3 8 -7.45 ( m, 2 H) 7.53 ( s, 4 H) 7.75.7 8〇( m, 1 H) 8.2 8-8.3 3 ( m, 2 H) 8.3 3 -8.3 6 ( m, 1 H ) (7 2,2-Dimethyl-3-{[5-(4-{[(4-nitrophenoxy)carbonyl]amino}phenyl)pyridin-2-yl]oxanylpropionate methyl Add a solution of ester (-166-200918053 200mg, 〇.430mmol), 2-methoxy-5-methylaniline (65mg, 〇·473mm〇1) in chloroform (6ml) at room temperature. 12.12ml '0.860mmol) 'Stirring for 2.5 hours, adding water to the reaction mixture, extracting with ethyl acetate, washing with 1M sodium hydroxide aqueous solution and saturated brine, drying (anhydrous magnesium sulfate), filtered, After concentrating, the obtained residue was purified by sand-column column chromatography [NH-sand, elution, hexane: ethyl acetate=8:1 to 1:2] to give a pale brown amorphous 3- { [ 5-(4-丨[(2-methoxy-5-methylphenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy} -2,2-dimethyl Propionate methyl vinegar 140mg). (Example 4 4) According to the production method of Example 43, by using 2,3-dimethoxybenzamine, 2-chloroaniline, 3-ethylaniline, 3,5-monomethylamine, 2 4, dimethylaniline, 2-ethylaniline, cyclohexylamine substituted 2-methoxy-5-methylaniline' gave the following compound of the present invention. 3-{[5-(4-{[(2,3-dimethoxyphenyl)aminocarboxylic acid]]amino}phenyl) y-but-2-yloxy] -2,2-di Methyl propyl propionate (Compound No. 7 5 ) 3_{ 〔5_(4-{ 〔(2-Chlorophenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]oxy} 2,2-Dimethylpropionic acid methyl ester (Compound No. 76) 3·{ M-(4-{ 〔(3-Ethylphenyl)aminocarbamoyl)amino}phenyl)pyridine-2 -yloxy}-2,2-dimethylpropanoic acid ethyl ester (Compound- 167-200918053 No. 77) 3_{ 〔 5-(4-( 〔(3,5-Dimethylphenyl)amine Methylmercapto]amino}phenyl)pyridin-2-yl]oxanium-2,2-dimethylpropionic acid methyl ester (Compound No. 7 8 ) 3_{ [5-(4_{ 〔 (2, 4· dimethylphenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxan-2-,2-dimethylpropionic acid methyl ester (Compound No. 7 9 ) 3_丨[5_(4_{ 〔(2-ethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}-2,2-dimethylpropanoic acid methyl ester (compound number 80) 3_[(5_{4-[(cyclohexylaminomethylindenyl)amino]phenyl}pyridine-2-yl)oxy]_2, 2_Dimethylpropionic acid methyl ester (Compound No. 81) (Example 4 5 ) 3_丨[(2-Methoxy-5(methylphenyl)aminocarbinyl]amino}phenyl Manufacture of pyridin-2-yloxy}-2,2-dimethylpropionic acid (Compound No. 82) (1) in 2-(1,3-dioxolane-2-yl)_2_ Methylpropane-;!_ alcohol (patent literature: W005102977 reference) (45 3 mg, 31〇mm〇1) in dimethylformamide (丨ml) solution, add sodium hydride (add &amp;IL) under ice cooling动石鱲4 5 % ) ( 1 1 9 mg, 3 . I 0 mm ο I ), stirred under ice cooling for 10 minutes, the reaction solution was warmed to room temperature, and 5-bromo-2-chloroclidine (199 mg' l was added. .〇3mmol) 'at room temperature for 30 minutes' at an external temperature of 90 〇c for 2 hours. Add water to the reaction mixture, extract with ethyl acetate, dry (no-168-200918053 water magnesium sulfate), filter, concentrate After that, the residue obtained was purified by a silica gel column chromatography (developing solvent: hexane: ethyl acetate = 1 〇: ??? to 2: ???) to give 5-bromo-2-[ 2-( 1,3·Dioxolane-2-yl)-2-methylpropoxy]pyridine (275 mg)MS ( ESI/APCI Dual ) : 3 02 ( M+l ) 1H NMR ( 3 00 MHz, CDCI3) δ ppm ΐ·〇4 ( s,6 Η) 3.84-3.91 (m,2 H) 3.91-3.99 (m , 2 H) 4.i4(s, 2 H) 4.84 ( s, 1 H) 6.66 ( dd, J = 8_7, 0.6 Hz, 1 H) 7.62 ( dd J = 8.7, 2.6 Hz, 1 H ) 8. 1 7 ( dd, J = 2.6, 0.6 Hz, 1 h ) (2) in 5-bromo-2-[2-(1,3-dioxol-2-yl)-2-methylpropoxy Pyridine (263 mg, 0.87 mmol), 4-nitrophenylboronic acid (290 mg '1.74 mmol), 10% IG carbon (132 mg), and triphenylphosphine (46 mg '0-174 mmol) of ethanol (2.7 (ml), water (2.7ml) mixture 'Add sodium carbonate (738mg, 6.96mmol), stir at an external temperature of 85 ° C for 11 hours, add water and ethyl acetate to the reaction solution, filter with flurtzite, extract acetic acid After the ethyl ester layer was dried (anhydrous magnesium sulfate), filtered, and concentrated, the obtained residue was chromatographed on a silica gel column [developing solvent; hexane: ethyl acetate = 15 · · 1 to 6 : 1 Purification to give 2-[2-(1,3-dioxolane-2-yl)-2-methylpropoxy]-5-(4-nitrophenyl) as a pale yellow powder Pyridine (2 7 8 mg). MS ( ESI/APCI Dual ) : 3 45 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm l_〇8 ( s,6 H) 3.86-3.93 (m, 2 H) 3.94-4.01 (m , 2 H) 4.25 (s, 2 H) 4.88 ( s, 1 H) 6.85-6.91 ( m, 1 H ) 7.64-7.71 ( m, 2 H) -169- 200918053 7.80-7.86 (m, 1 Η) 8.27 -8.34 (m, 2 Η) 8.41-8.45 (m, 1 Η ) (3) on 2-[2-(1,3--oxocyclopentan-2-yl)-2-methylpropoxy Add a solution of -5-(4-nitrophenyl)digo (266111, 0.772111111〇1) in ethanol (1.8 m 1 ) and tetrahydrofuran (1 · 8 m 1 ) 0% platinum carbon (27 mg), stirred at room temperature for 15 hours under a hydrogen atmosphere, and the reaction solution was subjected to filtration of the fluorite, and the filtrate was concentrated by using a silica gel column chromatography. Solvent; hexane: ethyl acetate = 10: 1 to 2: 3] purified to give 4-{6-[2-(1,3-dioxolan-2-yl)-2 as a colorless powder -methylpropoxy]pyridin-3-yl}aniline (1 9 3 mg) ° MS ( ESI/APCI Dual ) : 3 15 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1_07 ( s ,6 H) 3.67-3.8 0 ( m, 2 H) 3.84-3.92 ( m, 2 H) 3.92-4.00 ( m, 2 H) 4.19 (s, 2 H) 4.89 (s, 1 H) 6.72-6.80 (m, 3 H) 7.29-7.3 6 ( m, 2 H) 7.71 ( dd, J = 8.6S 2.6 Hz, 1 H) 8.30 ( dd, J = 2.6, 0.7 Hz, 1 H ) (4) 4-{6-[2-(1,3-dioxol-2-yl)-2-methylpropoxy To a solution of pyridin-3-yl}aniline (190 mg, 0.604 mmol) in tetrahydrofuran (2 ml), triethylamine (0.084 ml, 0.604 mm 〇1), 2-methoxy-5-methyl Phenyl isocyanate (251 mg, 1.51 mmol) was stirred at room temperature for 15 hours, and the reaction mixture was concentrated. Purification to 2: 3], 1-(4- -170-200918053 { 6·[ 2-( 1,3-dioxolan-2-yl)-2-methyl Propoxy]pyridin-3-yl}phenyl)-3-(2-methoxy-5-methylphenyl)urea (223 mg) ° MS (ESI/APCI Dual): 478 (M+l), 476 ( Ml) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.08 ( s, 6 Η) 2.31 ( s, 3 H) 3.82 ( s, 3 H) 3.85-3.92 ( m, 2 H) 3.92-4.00 ( m , 2 H) 4.22 ( s, 2 H) 4.89 ( s, 1 H) 6.71 ( s, 1 H ) 6.74 - 6.85 ( m, 3 H) 7.13 ( s , 1 H) 7.47 ( s, 4 H) 7.76 (dd, J = 8.6, 2.6 Hz, 1 H) 7.93-7.95 ( m, 1 H) 8.33-8.36 (m, 1 H ) (5) at 1-( 4-{6-[2-(1,3-dioxol-2-yl)-2-methylpropoxy]pyridin-3-yl}phenyl)-3-(2-methoxy Water (1.2 ml) and p-toluenesulfonic acid monohydrate were added to a mixed solution of chloroform (202 mg, 0.423 mmol) in chloroform (2.4 ml) and acetone (3 2 m 1 ). (1 2 1 mg, 0 · 6 3 5 mm ο 1 ), heating and refluxing for 18 hours, adding water to the reaction mixture, extracting with ethyl acetate, drying (anhydrous magnesium sulfate), filtering, and concentrating, The residue obtained was purified by silica gel column chromatography (developing solvent; chloroform: ethyl acetate = 4:1 to 2:1) to afford 1-[4-[2-[2,2- Dimethyl-3-oxopropoxy)pyridin-3-yl]phenyl}-3-(2-methoxy-5-methylphenyl)urea (1.76 mg). 1H NMR ( 3 00 MHz, DMSO-d6) δ ppm 1.13 ( s, 6 Η) 2.24 ( s, 3 Η) 3.85 ( s, 3 Η) 4.38 ( s, 2 Η) 6.72-6.78 (m, 1 Η) 6.83-6.92 ( m, 2 Η) 7.51-7.62 ( m, 4 Η) 7.95-8.01 ( -171 - 200918053

m, 2 Η ) 8.18-8.22 ( m,1 Η ) 8.41-8.45 ( m χ H 9.44 ( m, 1 H ) 9.62 ( s, 1 H ) (6) at l-{4-[6-(2, 2-Methyl-3-oxopropoxy D D-3-yl]benzyl} ·3_(2-methoxy-5-methylphenyl)urea (0_0692 mmol) in chloroform (1 ml) Add benzoic acid (18mg, 〇.l〇38mmol) to ice-cold butyl, stir at room temperature for 15, j, add m-chloroperbenzoic acid (I2mg, 0.069mm〇l) at room temperature to disturb the reaction solution. From the obtained residue, the Shixi rubber tube (developing solvent; chloroform: ethyl acetate = 5:1 to 1:1), gastric-grade thin layer gelatin chromatography [developing solvent; chloroform: methanol = 丨5:; To give a colorless powder of 3-{[5-(4-{[(2-methoxy-5)aminomethylindolyl]amino phenyl)pyridin-2-yl]oxy}methylpropionic acid (8 mg) ° (Example 46) 3-{[ 5-(4-丨[(2-methoxy-5-methylphenyl)aminomethylamino}phenyl)pyrrole 11 Oxy} _2,2-dimethylpropionic acid (No. 8 2 ) is produced in 3-{ 〔5-(4-{ 〔(2-methoxy-5-methylphenyl) oxy)amine }}phenyl) D D定_2-yl] oxindole-2,2_dimethyl vinegar (137m g, 〇.296 nimol) in a mixed solution of tetrahydrofuran (2 ml) and 1 m 1 ) was added with 6 M aqueous sodium hydroxide solution (0, stirred at room temperature for 8 hours, and neutralized by adding 1 Μ solution under ice cooling in the reaction solution, After extraction with ethyl acetate, 'by drying (anhydrous sulphur [)9.41-, yl) pyridyl 30 mg, m-chloro, over 1 hour: column chromatography: preparative [] purification - methylbenzene -2,2-dimercapto] Compound Aminomethylmethionate ( • 4 9ml) Magnesium Hydrate Hydrochloride) -172- 200918053 , filtered and concentrated to give 3-{[4-(4- { [(2-Methoxy-5-methylphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}-2,2-dimethylpropanoic acid (125 mg). (Example 47) According to the production method of Examples 43, 46, by using 2,3-dimethoxyaniline, 2-chloroaniline, 3-ethylaniline, 3,5-dimethylaniline, 2, The following compounds of the present invention were obtained by substituting 4-dimethylaniline, 2-ethylaniline or cyclohexylamine for 2-methoxy-5-methylaniline. 3-{[5-(4-{ 〔(2,3-Dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy} -2,2-dimethyl Propionate (Compound No. 83) 3-{[5-(4-{ 〔(2-Chlorobenzyl)aminoglycanyl]amino}phenyl)pyridin-2-yl]oxy} -2,2 -Dimethylpropionic acid (Compound No. 84) 3-丨[5-(4-{[(3-ethylphenyl)aminocarbamimidyl]amino}phenyl)pyridin-2-yl]oxy} -2,2-Dimethylpropionic acid (Compound No. 85) 3- { 〔 5-(4-{[(3,5-Dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridine 2-yl]oxy}-2,2-dimethylpropanoic acid (Compound No. 86) 3-{[5-(4-{[(2,4-Dimethylphenyl)aminocarbamyl] Amino}phenyl)pyridin-2-yloxy}-2,2-dimethylpropanoic acid (Compound No. 87) 3- { [5-(4-{ 〔(2-ethylphenyl)amino group Methylamino]amino}phenyl)pyridin-2-yloxy}-2,2·dimethylpropionic acid (Compound No. 88) -173 - 200918053 3 -[ (5 - { 4-[(cyclohexyl) Aminomethylmercapto)amino]phenyl}pyridine-2-yl)oxy]-2,2-dimethylpropanoic acid (Compound No. 89) (Example 4 8) 3-{[5-(4-{[(2,4-Dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy} -2,2_2 The sodium methylpropionate salt (Compound No. 90) is produced from 3-{[5-(4-{[(2,4-dimethylphenyl)aminocarbinyl]amino}phenyl) Addition of 40% hydrogen to a suspension of ethanol (2 1 · 3 m 1 ) of pyridin-2-yl]oxy}-2,2-dimethylpropanoic acid (4.4 g, 1 0 · 2 mm ο 1 ) An aqueous solution of sodium oxide (〇6 6 ml) was stirred at 25 ° C for 40 minutes at room temperature, stirred at 11 ° C for 40 minutes, and stirred at 0 ° C for 60 minutes, and the obtained individual was filtered off. It was washed with ice-cold ethanol (6.5 ml) to give 3-{[5-(4-{[(2,4-dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridine as a colorless powder. 2-yloxy}-2,2-dimethylpropanoic acid sodium salt (4.08 g) ° (Example 49) 1- ( { 〔 5- ( 4- { 〔( 2,4-dimethylphenyl) Manufacture of (amino)methylamino]amino}phenyl)pyridin-2-yloxy]methyl)cyclopropanecarboxylic acid (Compound No. 9 1 ) (1 ) in 2,5-dibromopyridine 1 -oxidation a solution of (8 1 5 mg, 3 2 3 mmo 1 ) in toluene (16 ml), Benzyl 1-(hydroxymethyl)cyclopropanecarboxylate (1.33 g, 6.45 mmol) and potassium carbonate (891 mg, -174-200918053 6.45 mmol) were heated under reflux for 24 hours, and the reaction solution was cooled to room temperature. , Florite filtration, concentrated filtrate 'The residue obtained was chromatographed on a silica gel column [developing solvent; hexane: ethyl acetate = 1: 1 to 〇: 1, ethyl acetate: methanol = 5 0: 1 Purification gave 1-{[(5-bromo-1 -oxypyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid benzyl ester (178 mg). MS ( ESI ) ': 378 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.13-1.22 ( m, 2H ) 1.42-1.51 ( m, 2H) 4.52 ( s, 2H) 5.13 ( s, 2H 6.75 ( d, J = 8.7 Hz, 1H) 7.18 ( dd, J = 2.4 Hz, 8.7 Hz, 1H ) 7.23-7.52 ( m, 5H) 8.30 ( d, J = 2.4 Hz, 1H) (2) at l -{[(5-Bromo-1-Oxylpyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid benzyl ester (178 mg, 0.471 mmol) in ethanol (6 ml) was added to the group hexamethylene ( 137 mg, 0.518 mmol), heating under reflux for 1.5 hours, cooling the reaction mixture to room temperature, filtering the flurtzite, concentrating the filtrate, and diluting the obtained residue with ethyl acetate, and using water and saturated brine. After washing, the organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated, and then purified and purified to silica gel column chromatography (hexane: ethyl acetate = 4:1) to afford 1 - { 5-Bromopyridine-2-yl)oxy]methyl}cyclopropane residual acid to base vinegar (lllmg). MS ( ESI ) : 3 62 ( M+l ) 1H NMR ( 300 MHz, CDC13) δ ppm 1.01-1.12 ( m, 2H ) 1.3 8- 1.49 ( m, 2H ) 4.47 ( s, 2H) 5.15 ( s, 2H 6.66 ( d, J = 8.7 Hz, 1H) 7.22-7.50 ( m, 5H) 7.63 ( dd, J = 2.4 Hz, 8.7 Hz, 1H) 8.14 ( d, J = 2.4 Hz, 1H) -175 - 200918053 ( 3) 1-{[(5-Bromopyridin-2-yl)oxy]methyl}cyclopropane residual acid benzyl ester (ll〇mg, 0.304mm〇l), 4-nitrophenylboronic acid (52.8mg) , 0.3 3 4 mmol ), palladium(II) acetate (6.8 mg, 0.03 0 mmol), triphenylphosphine (2 3.9 mg, Ο Ο 9 1 mm ο 1 ) in dioxane solution (2 ml), at room temperature 2M sodium carbonate aqueous solution (0.75 9ml '1.52mmol) was added, and stirred at 80 ° C for 1.5 hours under nitrogen atmosphere. After cooling to room temperature, the reaction solution was diluted with ethyl acetate to dilute the organic layer with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated, and the obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 5:1). 1-( { 〔 5-(4-nitrophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylate Benzyl ester (75 mg) 〇MS ( ESI ) : 405 ( M+ 1 ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1.10 ( dd, J = 4.4 Hz, 7.4 Hz, 2H) 1.45 ( dd, 3 = 4.4 Hz , 7.4 Hz, 2H) 4.57 (

s, 2H) 5.17 ( s, 2H) 6.87 ( d, J = 8.7 Hz, 1H) 7.31 ( s, 5H

) 7.68 ( d, J = 8.9 Hz, 2H ) 7.83 ( dd, J = 2.7 Hz, 8.7 Hz, 1H ) 8.3 1 ( d, J = 8.9 Hz, 2H ) 8.39 ( d, J = 2.7 Hz, 1H ) ( 4) In a solution of 1-({[ 5-(4-nitrophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylate (75 mg, 0.18 6 mmol) in ethanol (1 ml) Into the water (0.1ml), iron powder (103mg, 1.86mmol), concentrated hydrochloric acid (0.0 1ml), stirred at 80 ° C for 1 hour, the reaction solution was allowed to cool to room temperature, filtered with fluorite The solid was concentrated, the filtrate was concentrated, and the residue was diluted with ethyl acetate and sodium hydrogen carbonate aqueous solution. -176-200918053 The organic layer was washed with saturated aqueous sodium hydrogen carbonate and brine and dried over anhydrous magnesium sulfate After the layer, the mixture was filtered and concentrated. The residue obtained was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 3:1) to give 1-({ [ 5-(4-aminophenyl) Benzyl-2-yloxy]methyl)cyclopropanecarboxylate (49 mg) ° 1H NMR (3 00 MHz, CDC13) δ ppm 1.09 (dd, J = 4.4 Hz, 7.4 Hz, 2H) 1.42 ( Dd, 3 = 4.4 Hz, 7.4 Hz, 2H) 3.68-3.82 ( br, 2H 4.52(s, 2H ) 5.17(s, 2H) 6.72-6.84 (m, 3H) 7.21-7.41 ( m, 7H ) 7.67-7.78 ( m5 1H) 8.21-8.31 ( m, 1 H ) (5) at 1 -({[5-(4-Aminophenyl)-dip-2-yl]oxy}methyl)cyclopropanecarboxylic acid benzyl ester (49mg, 0.131mmo1) in chloroform (1ml) solution under ice cold Add pyridine (〇·〇1 6m), 〇·1 96mmol), and 4-nitrophenyl chloroformate (29mg, 0.145mmol) 'stirred at this temperature for 1 hour' to add three to the reaction solution. Ethylamine (0.027 ml '0.1 96 mmol) and 2,4-dimethylaniline (0.01 9 ml, 0.157 ramol) were stirred at room temperature for 19 hours, and the reaction mixture was diluted with ethyl acetate. After washing with saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogencarbonate solution and saturated brine, the organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography [NH. 1 : 1] Purification 'obtained 1 - ( ( 5 - ( 4 - { 〔 ( 2,4 - dimethylphenyl) amide yl) base group} base) 卩 卩疋-2-yl Oxy]methyl)cyclopropanecarboxylic acid benzyl ester (47.5 mg). MS ( ESI ) : 522 ( M + 1 ) , 520 ( Μ-1 ) -177 - 200918053 1H NMR ( 3 00 MHz, DMSO-D6) δ ppm 1_〇9-1·34 ( m, 4H ) 2.23 ( s, 3H) 2.25 ( s, 3H) 4.47 ( s, 2H) 5.14 ( s, 2H) 6.8 3 -7.0 5 ( m,3H) 7.22-7.42 ( m,5H) 7.55 ( d, J = 9.0 Hz, 2H 7.59 ( d, J = 9.0 Hz, 2H) 7.68 ( d, J = 8.4 Hz, 1H) 7.89 ( s, 1H) 7.98 ( dd, J = 2.4 Hz, 8.4 Hz, 1H) 8.41 (d, J = 2.4 Hz, 1H ) 9.06 ( s, 1H ) (6) in 1-({[5-(4-{[(2,4-dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridine A mixed solution of benzyl-2-yloxy]methyl)cyclopropanecarboxylate (47.5 mg, 0.091 mmol) in tetrahydrofuran (2 ml) and methanol (1 ml) was added 6 m aqueous sodium hydroxide (0.5 ml) After stirring at room temperature for 6 hours, the reaction mixture was neutralized with 1 Μ hydrochloric acid, diluted with ethyl acetate, and the organic layer was washed with saturated brine and water, and then the organic layer was concentrated, and the solid formed was suspended. The mixture was turbid with ethyl acetate, and the solid was filtered to give 1-({[(4-{[(2,4-dimethylphenyl)aminomethyl)]amino}phenyl) as a colorless solid. Pyridine-2 _ base] Oxygen}methyl)cyclopropanecarboxylic acid (30.6 mg). (Example 50) According to the production method of Example 49, benzyl b-(hydroxymethyl)cyclopropanecarboxylate was substituted with benzyl 1-(hydroxymethyl)cyclobutanecarboxylate, and used. 2-chloro-4-fluoroaniline, 3,5-dimethylaniline, 2-methoxy-5-trifluoromethylaniline, 2,3-dimethoxyaniline substituted 2,4-dimethylaniline The following compounds of the invention were obtained. 1_({[5_(4-{[(2,4-dimethylphenyl)aminomethylindolyl]amine-178- 200918053 yl}phenyl)pyridin-2-yl]oxy}methyl)cyclobutane Alkanecarboxylic acid (Compound No. 92) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]oxy }Methyl)cyclopropanecarboxylic acid (Compound No. 93) 1-({[5-(4-{[(3,5-Dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridine- 2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 94) 1-[({5-[4-( { [2-methoxy-5-(trifluoromethyl)phenyl])) Mercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 9 5 ) 1- ( { 〔5-(4-{ 〔 (2,3-dimethyl Oxyphenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxanylmethyl)cyclopropanecarboxylic acid (Compound No. 9 6 ) (Example 5 1 ) 1-( { 〔5 -(4-{ 〔(2-Chlorophenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxaniummethyl)cyclopropanecarboxylic acid (Compound No. 97) (1) In 1-( { [ 5-(4-aminophenyl)pyridin-2-yl]oxy} A To a solution of benzyl cyclopropanecarboxylate (73.6 mg, 0.196 mmol) in tetrahydrofuran (0.54 ml), 2-chlorophenylisocyanate (0.02 8 ml &gt; 0.23 5 mmol), and stirred at room temperature for 5 hours. The liquid was diluted with ethyl acetate, and the organic layer was washed with water. The organic layer was dried over anhydrous sulfur-179-200918053 magnesium sulfate, filtered and concentrated, and the obtained residue was chromatographed on a silica gel column. :ethyl acetate = 3 : 1 to 2 : 1] Purified to give 1-({ [ 5-(4-{[(2-chlorophenyl)aminocarbamoyl]amino}phenyl)pyridine-2 -yl)oxy}methyl)cyclopropanecarboxylic acid benzyl ester (9 1.7 mg). MS (ESI): 528 (M+l), 5 26 ( Μ-1 ) 1 NMR (3 00 MHz, CDC13) δ ppm 1.03-1.11 ( m, 2H ) 1.3 7- 1.45 ( m, 2H) 4.54 ( s , 2H) 5.17 ( s5 2H) 6.67 ( s, 1H) 6.76-6.8 4 ( m, 1H) 6.97-7.10 ( m, 2H) 7.21-7.38 ( m, 7H) 7.44-7.54 ( m, 4H ) 7.73 -7.80 (m5 1H) 8.16-8.23 (m, 1H ) 8.26- 8.3 3 ( m, 1H ) (2) in 1-( { [ 5-(4-( 〔 chlorophenyl)aminocarbazide δ] a mixed solution of benzyl phenyl) pyridine-2-yloxy}methyl)cyclopropanecarboxylic acid benzyl vinegar (9l_7mg, 〇.i74mmol) in tetrahydrofuran (1.16ml) and methyl® C α·58ιη1 ) A 6 M aqueous sodium hydroxide solution (〇.29 ml) was added under ice-cooling, and the mixture was stirred at room temperature for 23 hr., and then the mixture was neutralized with 1 M hydrochloric acid and concentrated. The obtained suspension was added to water and filtered to give @M t? 'Two isopropyl ether was washed to give 1-(丨[5-(4-{[(2-chlorophenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl] as a colorless solid. Oxy)methyl)cyclopropanecarboxylic acid (64.9 mg). (Example 5 2) According to the production method of Example 51, the following compound of the present invention was obtained by substituting 2-ethylphenylisocyanuric acid for 2-chlorophenyl isocyanate. 1-180- 200918053 1-( {[-(4-{[(2-ethylphenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yloxyoxanyl)cyclopropanecarboxylate Acid (Compound No. 98) (Example 5 3 ) 3-[(5-{4-[(Benzylaminomethylmercapto)amino]phenyl}pyrimidin-2-yl)oxy]-2,2- Manufacture of methyl dimethylpropionate (Compound No. 99) (1) on 5-bromo-2-chloropyrimidine (250 g, 1 2 5 mm ο 1 ), 3-hydroxy-2,2-di Methyl propyl propionate (33. lg, 251 mmol), potassium carbonate (34.7 g, 251 mmol), and dimethyl bis-butylammonium iodide (92.6 g, 2 5 1 mm ο 1 ) The guanamine (500 m 1 ) suspension was stirred at an external temperature of 1 40 rpm for 3 hours, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, dried (MgSO4), filtered, and concentrated. The obtained residue was purified by a silica gel column chromatography (developing solvent; hexane:ethyl acetate = 1-5:1 to 3.5:1) to give a colorless powder of 3-[[ Oxy]-2,2-dimethylpropionic acid methyl ester (17_48§) ° MS ( ESI/APCI Dual ) : 2 8 9 ( Μ + 1 ) 1H NMR ( 3 00 MH z, CDC13) δ pPm i.34 ( s,6 H) 3.70 ( s, 3 H) 4.37 ( s, 2 H) 8_52 ( s, 2 H) (2 ) 3 -[ ( 5 -bromopyrimidine-2 -yl)oxy]-2,2-dimethylpropionic acid methyl ester (17.4 g, 60.14 mmol), 4-nitrophenylboronic acid (n.04 g, 66.16 mmol), palladium acetate (II) (L35 g, 6.01mmo1), and a mixture of 3M sodium carbonate aqueous solution (-181 - 200918053 150ml) and dioxane (350 ml) of triphenylphosphine (4.73g, 18.04mmol), and an external temperature of 8 (rc stirred for 30 minutes) Water and ethyl acetate were added to the reaction mixture, and the ethyl acetate layer was filtered, and the ethyl acetate layer was extracted, dried (anhydrous magnesium sulfate), filtered, and concentrated, and the residue obtained was chromatographed by a silica gel column. Solvent; hexane: ethyl acetate = 8:1 to 1:3] purified to give 2,2-dimethyl-3-{[ 5-(4-nitrophenyl)pyrimidine-2- Methyl oxy-propionic acid methyl ester (16.87g) MS ( ESI/APCI Dual) : 3 32 ( M+l ) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.38 ( s, 6 H) 3.72 ( s , 3 H) 4.48 ( s, 2 H) 7.67-7.73 ( m, 2 H) 8.33- 8.39 ( m, 2 H ) 8.77 ( s, 2 H ) (3) on 2,2-dimethyl-3- {[5-(4-Nitrate 1 〇% of a mixed solution of methanol (200 μm) and tetrahydrofuran (200 mmol) Platinum carbon (1 - 69 g) was stirred at room temperature for 20 hours under a hydrogen atmosphere, and the reaction mixture was filtered through celite, and the filtrate was concentrated, and the obtained residue was subjected to chromatography on a silica gel column (developing solvent; hexane: acetic acid) Ethyl ester = 4: 1 to 1: 5] Purified to give a pale yellow powder of 3-{[5-(4-aminophenyl)pyrimidin-2-yl]oxy}-2,2-dimethylpropanoic acid Methyl ester (14.2 g). MS ( ESI/APCI Dual ) : 302 ( M+l ) , 3 00 ( Ml ) 1H NMR ( 3 00 MHz, CDC13 ) δ ppm 1 .36 ( s, 6 H ) 3.71 ( s, 3 H) 3.75 -3.8 8 ( br, 2 H) 4.42 ( s, 2 H ) 6.74- 6.81 (m, 2 H) 7.28-7.35 (m, 2 H) 8.63 ( s, 2 H) (4 ) at 3- {[ 5- ( 4-aminophenyl)pyrimidin-2-yl]oxy}--182- 200918053 2,2-Dimethylpropionic acid methyl ester (44〇1^, 1.46111111〇1) in chloroform (0.9ml) Add 4-nitrophenyl chloroformate (338 mg '1.68 mm ο 1 ), batch (〇.2 ml, 1.97 mmol) under ice cooling, and stir for 1.5 hours in ice. Water was added, and the mixture was extracted with EtOAc. EtOAc (EtOAc m. Methyl-3-{[5-(4-{[(4-nitrophenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}propionic acid methyl ester (540 mg). 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.37 ( s, 6 Η) 3.71 ( s, 3 Η) 4.45 ( s, 2 Η) 7.09-7.14 ( br, 1 Η) 7.38-7.46 ( m, 2 Η) 7.49-7.62 ( m, 4 Η) 8.27-8.3 5 ( m, 2 Η) 8.70 ( s, 2 Η ) (5) in 2,2-dimethyl- 3-{ 〔5-(4-{ 〔 4-nitrophenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}propionic acid methyl ester (1 5 Omg '0.322mmol) in chloroform (3ml) solution, force [[entry Base amine (38 mg, 0.35 4 mmol), triethylamine (0.09 ml, 0.648 mmol), stirred at room temperature for 15 hours, water was added to the reaction mixture, extracted with ethyl acetate and dried (MgSO4 After filtration and concentration, the obtained residue was purified by silica gel column chromatography (developing solvent: hexane: ethyl acetate = 2:1 to 1:2) to give 3-( 5- {4-[(Benzylaminomethylmethyl)amino]phenyl}pyrimidin-2-yl)oxy]-2,2-dimethylpropanoic acid methyl ester (128 mg). (Example 54) -183-200918053 According to the production method of Example 53, the following compound of the present invention was obtained by substituting a benzylamine with a cyclohexylamine. 3-[(5-{4-[(Cyclohexylaminocarbamimidyl)amino]phenyl}pyrimidine-2-yl)oxy]-2,2-dimethylpropanoic acid methyl ester (Compound No. 100 (Example 5 5 ) 3- [( 5- { 4-[(benzylaminomethylmethyl)amino]phenyl}pyrimidin-2-yl)oxy]-2,2-dimethylpropanoic acid (Compound No. 1〇1) was produced from 3-[(5-{4-[(benzylaminomethylmethyl)amino]phenyl}pyrimidin-2-yl)oxy]-2,2-dimethyl A mixed solution of methyl propyl propionate (128 mg, 0.29 5 mmol) in tetrahydrofuran (1.8 ml) and methanol (1.8 ml) was added to a 6 Μ aqueous sodium hydroxide solution (0.49 m 1 ) and stirred at room temperature 2 After a few hours, a 2M aqueous solution of hydrochloric acid was added to the mixture, and the mixture was evaporated. Aminomethylmercapto)amino]phenyl}pyrimidin-2-yl)oxy]-2,2-dimethylpropanoic acid (82 mg). (Example 5 6) According to the production methods of Examples 53 and 55, the following compounds of the present invention were obtained by substituting benzylamine with cyclohexylamine. 3-[(5-{4-[(cyclohexylaminomethylamino)amino]phenyl}pyrimidin-2-yl)oxy]-2,2-dimethylpropanoic acid (Compound No. 1〇2) (Example 5 7 ) -184- 200918053 1-( { 〔5-(4-{ 〔(2-methoxy-5-methylphenyl)aminocarbamoyl)amino}phenyl)pyrimidine- Manufacture of 2-amino]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 1 〇3) (1) 5-Bromo-2-chloropyrimidine (727 mg, 3.758 mmol), 1-(hydroxymethyl)cyclopropane Benzyl carboxylate (1.55g, 7-516mmol), potassium carbonate (1.04g, 7.516mmol), and tetra-n-butylammonium compound (1.42g, 3.758mmol) in toluene (14.5ml) suspension 'external temperature The mixture was stirred at 40 ° C for 4 hours, and the reaction mixture was filtered through celite. After the filtrate was concentrated, the obtained residue was subjected to chromatography on a silica gel column (developing solvent; hexane: ethyl acetate = 15:1 to 3) 5: 1] Purification gave 1-{[(5-bromopyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylic acid benzyl ester (4 3 8 mg) as a pale yellow powder. MS ( ESI/APCI Dual ) : 3 63 ( M+l ) 1H NMR ( 300 MHz, CDC13) δ ppm 1.05-1.11 ( m, 2 H) 1.41-1.46 (m, 2 H) 4.53 (s, 2 H) 5.11 (s, 2 H) 7.23 - 7.3 4 ( m, 5 H ) 8.47 ( s, 2 H ) (2 ) 1-{[( 5-Bromopyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylate Benzyl acetate (410 mg, 1.129 mmol), 4-nitrophenylboronic acid (1 98 mg &gt; 1.85 mmol), palladium (II) acetate (25 mg, 0.1 129 mmol), and triphenylphosphine (89 mg, 0.3) 3 9mmol) 2M sodium carbonate aqueous solution (2.8ml), dioxane (8.2ml) mixture, stirring at 80 ° C for 30 minutes at ambient temperature, adding water and ethyl acetate to the reaction solution, filtering with flurtite After extracting the ethyl acetate layer, drying (anhydrous magnesium sulfate), filtration, and concentration, the residue obtained was chromatographed on a silica gel column [developing solvent; hexane-185-200918053 • ethyl acetate = 1 ο : 1 to 1: 4] Purification to give 1-({[5-(4-nitrophenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid benzyl ester (180 mg) as pale yellow powder. . MS ( ESI/APCI Dual ) : 406 ( M+l) 1H NMR ( 3 00 MHz, CDC13) δ ppm 1.10-1.15 ( m, 2 H) 1.45-1.50 (m, 2 H) 4.64 (s, 2 H) 5.13 (s, 2 H) 7.24-7.3 2 ( m, 5 H) 7.66-7.72 ( m, 2 H) 8.3 3 - 8.3 8 ( m, 2 H ) 8.74 ( s, 2 H ) (3 ) at 1 - ({[5-(4-Nitrophenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid benzyl ester (1 73 mg, 0.427 mmol) in ethanol (1 7.5 m 1 ), added 2 Μ hydrochloric acid aqueous solution (0.2 1 m 1 ), water (lml), and iron powder (238 mg, 4.2 7 mmol), heated under reflux for 1 hour, added water and ethyl acetate 'fluorine-stone filtration' to the reaction solution. The ethyl acetate layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine, and dried (MgSO.sub. - (4-Aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid benzyl ester (123 mg) ° MS ( ESI/APCI Dual ) : 3 76 ( M+l ) 1H NMR ( 200 MHz, CDC13) δ ppm 1.05-1.16 (m, 2 H) 1.38-1.50 ( m, 2 H) 3.76-3.85 ( br, 2 H) 4.59 ( s, 2 H ) 5.13 ( s , 2 H) 6.72-6.83 (m, 2 H) 7.23-7.35 (m, 7 H) 8.61 ( s, 2 H ) (4 ) in 1 - ( { [ 5 - ( 4 -aminophenyl) pyrimidine - 2-Benzyloxy}methyl)cyclopropanecarboxylic acid benzyl ester (12 mg, 〇.32 mmol) in chloroform (-186-200918053 2.4 ml) was added to the pyridine (〇.〇43ml, 4-Nitrophenyl chloroformate (74 mg, 0-37 mmol) &gt; 1.5 hours, and triethylamine (〇·〇8 9 m 1 , 2-methoxy-5-methyl) was added under ice cooling. Aniline (48 mg, 0.35 mmol, stirring at 40 ° C for 1 hour, adding water to the reaction solution, washing with acetic acid, using 1 Μ aqueous sodium hydroxide solution, 1 Μ hydrochloric acid aqueous solution, saturated solution, saturated brine, and drying ( After anhydrous sulfuric acid and concentration, the obtained residue was gelled with a silica gel column to develop a solvent; hexane:ethyl acetate = 4:1 to 1: / / to pale yellow amorphous 1-( { [5 -(4-{[(2-Phenylphenyl)aminocarbamoyl]amino}phenyl)pyrimidin-2-yl)cyclopropanecarboxylic acid benzyl ester (142 mg). MS ( ESI/APCI Dual ) : 5 3 9 ( M+l ) , 537 1H NMR ( 3 00 MHz, DMS 0-d6 ) δ ppm 1 . 2 H) 1.27- 1.3 3 (m, 2 H) 2.24(s , 3 H) 3.8: 4.52 (s, 2 H) 5.12 (s, 2 H) 6.72-6.79 (m,] d, J = 8.2 Hz, 1 H) 7.24-7.3 5 ( m, 5 H) 7.54-7 ) 7.98-8.01 (m, 1 H) 8.22 (s, 1 H) 8.87 (s (s, 1 H ) (5 ) in 1- ( { 〔 5- ( 4- { 〔 (2-methoxy.) a mixture of tetrahydroanthracene and methanol (1 m 1 ) in a mixture of benzylaminomethylamino}phenyl)pyrimidin-2-yloxy]carboxylate (137 mg, 0.254 mmol), 6 Hydrogen oxyhydroxide (0.42 ml), stirred at room temperature for 1 hour, 0.43 mm in the reaction solution, 1) stirred at room temperature, 0.35 m mo 1 )), extracted with ethyl ester at room temperature and magnesium carbonate, Filtration of F (N.sub.) to give methoxy-5-methyl]oxy}methyl (Μ-1) 14-1.21 (m, 5 ( s, 3 Η ) I Η) 6.90 ( •69 (m , 4 Η , 2 Η ) 9.47 -5-Methylphenylmethyl)cyclopropane and methane (1 ml) aqueous sodium solution was added to ice-cold-187-200918053 1M aqueous hydrochloric acid solution extracted with ethyl acetate, dried (anhydrous Magnesium sulfate), filtered, concentrated The residue was prepared by preparative thin-layer chromatography on silica gel (developing solvent; chloroform:methanol = 1 〇: 1) to obtain 1-( { _5_(4_{ 〔(2-methoxy-5-methyl) as a colorless powder. Phenyl)aminomethylmercapto]aminoindole phenyl)pyrimidin-2-yl]oxanylmethyl)cyclopropanecarboxylic acid (1 Omg). (Example 5 8 ) { 〔5-(4-{ 〔(4-Chloro-3-fluorophenyl)carbonyl]amino}phenyl)pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid Production of methyl ester (Compound No. 104) (Chemical Formula 1)

In a solution of 1-({[5-(4-aminophenyl)pyridinyloxy)methyl)cyclobutanecarboxylic acid methyl ester (200 mg, 0-640 mm 〇l) in tetrahydrofuran (6.0 ml) , 1-(3-dimethylaminopropyl)_3_ethylcarbodiimide hydrochloride (184 mg, 0-960 mmol) and 4-chloro-3-benzoic acid (1 17 mg, 0.672 mm〇l), After stirring at room temperature for 2 hours, a 1 Μ aqueous hydrochloric acid solution was added to the reaction mixture, and extracted with ethyl acetate. Then, it was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine, and dried (g^ &gt; After concentration, a colorless powder is obtained. ({ [ 5 _ ( 4 _ 丨 [(4-chloro-3-fluorophenyl)carbonyl]amino}phenyl)pyrrole_2_yloxy}methyl Cyclobutanecarboxylic acid methyl ester (296 mg). -188- 200918053 (Example 5 9) According to the production method of Example 58, by using 丨_( { 〔5-(4-aminophenyl)pyridine- 2-yloxy]methyl)cyclobutanecarboxylic acid methyl group (Refer to Synthesis Example 3-1) 'Or replaced with use〗 _( { _5_(4_Amino_3_fluorophenyl)pyridine- 2-methyl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Reference Synthesis Example 3-12), 1-(丨[5- (4- Aminophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (Reference Synthesis Example 3-2) ' 3- {[ 5- ( 4 -Aminophenyl)pyridine-2- Methyl oxy] -2,2-dimethylpropionic acid methyl ester (synthesized according to the synthesis method of Reference Synthesis Example 2-1 and Reference Synthesis Example 3-1), 1-( { [5-(4-amine) Methyl phenyl)pyrimidin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (Reference Synthesis Example 3-7), 1-( { _5_(4_yenylphenyl)pyrimidine-2 -yloxy}methyl)cyclopropanecarboxylic acid methyl ester (synthesized according to the production method of Reference Synthesis Example 3-6), and 3_{[5-(4-aminophenyl)pyrimidin-2-yl] Oxygen} _2,2-dimethyl propionate methyl ester (synthesized according to the method of Example 2): using 3,4-diethylbenzoic acid' or using 4-fluoro-3-methylbenzene Formic acid, 3-fluoro-4-methylbenzoic acid, 4-fluoro-3-(trifluoromethyl)benzoic acid, 2-fluoro-4-(trifluoromethyl)benzoic acid, 3,5-difluorobenzene Formic acid, 2,2-difluoro-1,3-benzodioxan-5-carboxylic acid, 2-fluoro-3-(trifluoromethyl)benzoic acid, -189- 200918053 2,3-difluorobenzene Formic acid, 2-fluoro-5-(trifluoromethyl)benzoic acid, 3-(trifluoromethoxy) Benzoic acid, 2-chloro-4,5-difluorobenzoic acid, 3-chloro-4-methylbenzoic acid, 3-fluorobenzoic acid, 3-(1,1,2,2-tetrafluoroethoxy Benzoic acid, 3,4-dimethoxybenzoic acid, 4-methoxy-3-methylbenzoic acid, or 4-chloro-3-(trifluoromethyl)benzoic acid, the following Inventive compound. 1-( { [ 5 - ( 4 - { 〔(3,4 - _ethylphenyl) decyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl Ester (Compound No. 1 〇5 ) 1-( { 〔5-(4-{ 〔(4-Fluoro-3-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl Cyclobutanecarboxylic acid methyl ester (Compound No. 106) 1-( { 〔5-(4-{ 〔(3-Fluoro-4-methylphenyl)carbonyl)amino}phenyl)pyridine-2- Methyl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 107) 1-[({5-[4-( { [4-fluoro-3-(trifluoromethyl)phenyl]carbonyl)} Amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 〇8) 1-[ ( {5-[4-( { 〔2 - gas - 4 -(difluoro!methyl)phenyl]fluorenyl} -190- 200918053 Amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 〇9) 1-( { 〔5-(4-{ 〔(3,5-Difluorophenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester ( Compound No. 110) 1-( {[ 5-(4- { 〔(2,2 - I··-1,3-Benzene- Ethyl-5-yl)mineyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (compound No. 1 1 1 ) 1_[ ( {5-[4- ({[2-Fluoro-3-(trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 1 2) 1-({[5-(4-{[(2,3-difluorophenyl)ornyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Base vinegar (Compound No. 113) 1- [({5-[4-( { [2-fluoro-5-(trifluoromethyl)phenyl)carbonyl)amino)phenyl]pyridin-2-yl}oxy )methyl]cyclobutane residual acid methyl vinegar (Compound No. 1 1 4 ) 1-[({5-[4-( { 〔3-(Trifluoromethoxy)phenyl)]indenyl) Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl vinegar (Compound No. 1 15) 1- ( { 〔 5-( 4-丨[(2-chloro-4,5-) Difluorophenyl) benzyl] phenyl) pyridine-2-yloxy}methyl) Cyclobutanine Residual Methyl vinegar (Compound No. 1 16) 1- ( { 〔 5- ( 4- { 〔(3-Chloro-4-methylphenyl)- yl}}-phenyl-191 - 200918053 base) Methyl 2-pyridine-2-yloxyoxomethyl)cyclobutanecarboxylate (Compound No. 117) 1-( { 〔 5-(4-{ 〔(3-Fluorophenyl)carbonyl)amino}phenyl Pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 1 18 ) Bu [({5-[4-( { 〔3-(1,1,2,2-4) Fluoroethoxy)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 1 9 ) 1-({[5-( 4-{[(3,4-Dimethoxyphenyl)carbonyl]amino}phenyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 120) 1- ( {[5-(4-{ 〔(4-methoxy-3-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl Ester (Compound No. 1 2 1 ) 1_( { 〔5-(4-{ 〔(3 -Chloro-4-methylphenyl)carbonyl)amino} _3_ fluorophenyl)pyridine-2-yloxy} Methyl cyclobutanecarboxylic acid methyl ester (Compound No. 1 2 2 ) 1-[({5-[4-( { 〔4-chloro-3-(trifluoromethyl)phenyl)carbonyl)amino) Phenyl]pyridin-2-yl}oxy)methyl]cyclopropene residue methyl ester Compound No. 1 2 3 ) 1-[( { 5-[ 4-( { 〔3-(Trifluoromethoxy)phenyl)carbonylguanidino)phenyl]pyridin-2-yl}oxy)methyl] Methyl cyclopropanecarboxylate (Compound No. 1 2 4 ) 1-( { 〔5-(4-{ 〔(4-Fluoro-3-methylphenyl)carbonyl)amino benzene-192- 200918053 base) Pyridin-2-yl]oxy)methyl)cyclopropanecarboxylic acid methyl ester (Compound No. 125) 1-( { 〔5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl)amine Methyl phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylate (Compound No. 126) 3-( {5-[4-( { [4-Chloro-3-(trifluoromethyl) Methyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)-2,2-dimethylpropanoic acid methyl ester (Compound No. 127) 3-{ [5-(4-{ 〔 (3-Chloro-4-methylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}-2,2-dimethylpropanoic acid methyl ester (Compound No. 128) 1-[ ( {5-[4-( { chloro-3-(trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl Ester (Compound No. 1 2 9 ) 1-[ ( {5-[4-( { 〔3-(Trifluoro Oxy)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 3 0 ) 1-( { 〔5-(4- {[(4-Fluoro-3-methylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 1 3 1 ) 1- ( {[5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl)aminopurinylphenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester ( Compound No. 132) 1-[({5-[4-( { [4-Chloro-3-(trifluoromethyl)phenyl)carbonyl]-193 - 200918053 Amino)phenyl]pyrimidin-2-yl} Oxy)methyl]cyclopropanecarboxylic acid methyl ester (Compound No. 1 3 3 ) 1-[({5-[4-( { [3-(Trifluoromethoxy)phenyl]carbonyl)]amino)benzene Methylpyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid methyl ester (Compound No. 1 3 4 ) Bu ({ 〔5-(4-{ 〔(4-Fluoro-3-methylphenyl)) Carbonyl]amino}phenyl)pyrimidin-2-yl]oxo}methyl)cyclopropanecarboxylic acid methyl ester (Compound No. 1 3 5 ) 1- ( { C 5- ( 4- { 〔 (3-Chloro-) 4-methylphenyl)carbonyl]amino}phenyl) Methyl pyridine-2-yloxy}methyl)cyclopropanecarboxylate (Compound No. 1 3 6 ) 3-( {5-[4-( { 〔4-Chloro-3-(trifluoromethyl)benzene) Methyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)-2,2-dimethylpropanoic acid methyl ester (Compound No. 137) (Example 60) 1-( { 〔5- (4-{ 〔(3,4-Dimethylphenyl)carbonyl]amino}phenyl) rylos-2-yloxy}methyl)cyclobutanyl acid methyl vinegar (Compound No. 1 3 8 Manufacturing (化102)

4-({[5-(4-Aminophenyl)pyridine-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (10 mg, 0.320 mmol) in tetrahydrofuran (-194- 200918053 2_0ml), 3,4-dimethylbenzimidium chloride (5411^, 0.320mmol) was added, and stirred at room temperature for 20 hours. A saturated aqueous solution of sodium hydrogencarbonate was added to the mixture and the mixture was extracted with ethyl acetate. Washed with saturated brine, dried (anhydrous magnesium sulfate), filtered, and concentrated to give 1-[(5-(4-{[(3,4-dimethylphenyl)carbonyl)] Amino}phenyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (120 mg). (Example 61) According to the production method of Example 60, 1-({[5-(4-aminophenyl)pyridin-2-yl)oxy}methyl)cyclobutanecarboxylic acid methyl ester (reference) Synthesis Example 3-1), or alternatively, using 1·(5-(4-amino-2-fluorophenyl)pyridin-2-yl]oxaniummethyl)cyclobutanecarboxylic acid methyl ester ( Reference Synthesis Examples 3-9), 1-({[ 5-(4-Amino-3-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Reference Synthesis Example) 3-12), 1-({[5-(4-Aminophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (Reference Synthesis Example 3-2), 1- ( {[ 5-(4-Aminophenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid methyl ester (Reference Synthesis Example 3-4), 3- { [5-(4-amine Phenylphenyl)pyridin-2-yloxy}-2,2-dimethylpropionic acid methyl ester (synthesized according to the synthesis method of Reference Synthesis Example 2-1 and Reference Synthesis Example 3-1), { 〔5 -(4-fl female base) 13⁄4卩疋-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-7), 1-( { [5-(4-amine) 3--3-fluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Base ester (Reference Synthesis Example 3-13), 1-({[ 5-(4-aminophenyl-195- 200918053))pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (based on Synthesized by the production method of Synthesis Example 3-6, 1 - ( { 〔5 - ( 4 -aminophenyl)pyrimidin-2-yl)oxy}methyl)cyclopentanecarboxylic acid methyl ester (reference synthesis Example 3-8) and 3-{[ 5-(4-aminophenyl)pyrimidin-2-yl]oxy}-2,2-dimethylpropionic acid methyl vinegar (manufacturing method according to Example 2) Synthetic); use (4-fluorophenyl)acetamidine chloride, or use 3.4-dimethylbenzhydryl chloride, 3.4-dichlorobenzamide chloride, 2.3-dimethylbenzimid chloride, cyclohexyl Alkylcarbonyl chloride, Cai-2 - Tengqi gas, 3-chloro-4-fluorobenzhydrazide chloride, benzamidine chloride, 4-ethylbenzylidene chloride, 4-methyl-3-yl (trimethyl) Benzoyl chloride, 3-fluoro-4-(trifluoromethyl)benzhydrazide chloride, 3-chlorobenzhydryl chloride, 3-(trifluoromethyl)benzoic acid chloride, 4-gas-2-(three Gas methyl) benzamidine chloride, 3.5-dichlorobenzhydryl chloride, 2.5-difluorobenzhydryl chloride, 2.4-difluorobenzhydryl chloride, 3.4-difluorobenzhydryl chloride, 4_(three gas Oxy phenyl) Chloride, 200918053 3-methoxybenzimid chloride, 3-methylbenzimidium chloride, or 3-(trifluoromethoxy)benzimid chloride' gives the following compounds of the invention. 1_( { 〔 5_ ( 4 _ { 〔 4-(4-Phenylphenyl) ethinyl)amino phenyl) pyridin-2-yloxy]methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 139) 1-({[5-(4-{[(3,4-dichlorophenyl)]]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl vinegar (Compound No. 140) 1-({[5-(4-{[(2,3-Dimethylphenyl))]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutane Methyl alkanoate (Compound No. 1 4 1 ) 1- { 〔( 5- { 4-[(cyclohexylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylate Acid methyl ester (Compound No. 142) 1-{ 〔(5-{4-[(Naphthalen-2-ylcarbonyl)amino)phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid Methyl ester (Compound No. 143) b( { 〔5-(4-{ 〔(3-Chloro-4-fluorophenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl) ring Methyl butanecarboxylate (Compound No. 144) [(5-{4-[(Phenylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid methyl ester (Compound No. 1 45 ) { 〔5-(4-{ 〔 (4-ethyl Methyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 146) -197- 200918053 !_[ ( {5·[ 4-( { [4-Methyl-3-(trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridine-2-yloxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 147) 1_ [({5-[4-( { 〔4-fluoro-4-(difluoromethyl)))] peramino}phenyl]pyridin-2-yl}oxy)methyl]cyclobutanthine Acid methyl ester (compound No. 1 4 8 ) 1·(丨[5-(4-{ 〔(3-chlorobenyl)) yl]fl-enylhydrazino-yl)-pyridin-2-yl]oxypurine Residue acid methyl ester (Compound No. 149) [(丨5-[4-({[3-(Difluoromethyl)phenyl))]amino)phenyl]pyridine-2- Methyl}oxy)methyl]cyclobutane residual acid methyl ester (Compound No. 1 50) ^[( { 5_[ 4· ( { 〔4-fluoro-2-(trifluoromethyl)phenyl)carbonyl) Amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanoic acid methyl ester (Compound No. 1 5 1 ) 1_(丨[5_(4-{[(3,5-Dichlorobenzene) Alkyl phenyl)pyridine-2- Methoxy]methyl)cyclobutanine residual acid methyl vinegar (Compound No. 152) 1- ( {[ 5- ( 4- {[ ) ) D-but-2-yl]oxy} A (2,5-II Fluorophenyl)carbonyl]aminoindole phenyl phenyl)-cyclobutanecarboxylic acid methyl ester (Compound No. 153) 1- ( { 〔 5_ ( 4- {[ ) Π Π -2 -2- yl) oxy} A 2 4-difluorophenyl)ornyl]amino}phenyl_&gt; cyclobutanecarboxylic acid methyl ester (Compound No. -198-154) 200918053 1-({[5-(4-{[(3) ,4-difluorophenyl)carbonyl]amino phenyl)pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 155) 1_[ ( {5-[4-( {[4-(Trifluoromethoxy)phenyl]decyl decylamino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 56 ) 1- ({[5-(4-{[(3-methoxyphenyl)carbonyl]amino)phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 157 1-( { 〔5-(4-{ 〔(3-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (compound) No. 158) 1_[({5-[2-Fluoro-4-({[3-(3) Fluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 5 9 ) 1-[({5-[3 -fluoro-4-({[3-(trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 1 6 0 ) 1-({[5-(4-{[(3,4-dichlorophenyl)carbonyl]amino)phenyl)pyridin-2-yl]oxaniummethyl)cyclopropanecarboxylic acid methyl Ester (Compound No. 161) 1-({[5-(4-{[(3,4-Dimethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropane Carboxylic acid methyl ester (Compound No. 1 62 ) -199- 200918053 1-( { 〔5-(4-{ 〔(3-Chloro-4-fluorophenyl)carbonyl)amino}phenyl)pyridine-2- Methyl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (Compound No. 163) 1-[({5-[4-({[3-(Trifluoromethyl)phenyl)carbonyl)amino)phenyl) []pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid methyl ester (Compound No. 1 6 4 ) 1-[({5-[4-( { [3-(Trifluoromethyl)phenyl)] Carbonyl}amino)phenyl]pyridin-2-ylindoleoxy)methyl]cyclo Methyl pentanecarboxylate (Compound No. 1 65 ) 3-{ 〔5-(4-{ 〔(3,4-Dichlorophenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy} -2,2-Dimethylpropionic acid methyl ester (Compound No. 166) 2.2-Dimethyl-3-(indolyl 5-[4-({[3-(trifluoromethyl)phenyl)carbonyl)amine Phenyl]pyridin-2-yl}oxy)propionic acid methyl ester (Compound No. 167) 2.2-Dimethyl-3-({5-[4-({[3-(trifluoromethoxy))) Phenyl]carbonyl]amino)phenyl]pyridyl)oxy)propionic acid methyl ester (Compound No. 1 6 8 ) 1-( { 〔5-(4-{ 〔 (3,4-Dichlorophenyl) Carbonyl]amino}phenyl)pyrimidin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 169) 1-( { 〔5-(4-{ 〔 (3-chloro-4) -fluorophenyl)carbonyl]amino}phenyl)pyrimidin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. -200-170) 200918053 1-( { [ 5-(4 -丨[(3,4-dimethylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 171) 1_[(丨5-[3-fluoro-4-({[3-(trifluoromethyl)phenyl)carbonyl) } Amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl vinegar (Compound No. 1 7 2 ) 1-[ ( {5-[4-( { 〔3-(3 Fluoromethyl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 173) 1-({[5-(4-{ [(3,4-Dichlorophenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxanylmethyl)cyclopropanecarboxylic acid methyl ester (Compound No. 174) 1-( { 〔5-( 4-{[(3-Chloro-4-fluorophenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxanylmethyl)cyclopropanecarboxylic acid methyl ester (Compound No. 175) 1- ( {[ 5-(4-{((3,4-yl)pyrimidin-2-yl)oxy}methyl)dimethylphenyl)carbonyl]amino}benzoylpropanecarboxylic acid methyl ester (Compound No. 176 1-[({5-(4-( { 〔3)phenyl]pyrimidin-2-yl}[3_(trifluoromethyl)phenyl]carbonyl}amine-based stomach)methyl]cyclopropanecarboxylic acid Base ester (Compound No. 177) 1-[({ 5- 〔4-({I)Phenyl)pyrimidin-2-yl}oxy)(trifluoromethyl)phenyl]carbonyl}amino group] Cyclopentanecarboxylic acid methyl ester (Compound No. 1 7 8 ) -201 - 200918053 3-{[5_(4-丨[(3,4-Dichlorophenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy} -2,2-dimethyl Methyl propionate (compound No. 179) 2,2-Methyl-3-({5-[4-({[3-(trifluoromethyl)phenyl)carbonyl)amino)phenyl] Pyrimidine-2-yl}oxy)propionic acid methyl ester (Compound No. 180) 2,2-Dimethyl-3-({5-[4-({[3-(trifluoromethoxy)phenyl)] Carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)propionic acid methyl ester (Compound No. 8.1) (Example 62) 1_[({5-[4-( { [3-(methyl) Manufacture of methyl sulfonyl)phenyl]carbonyl}amino)phenyl]anthracene-2,yloxycarbonyl)methyl]cyclobutanecarboxylate (Compound No. 182)

(1) In a solution of 3-methylsulfonylbenzoic acid (gimg, 0.384 mmol) in tetrahydrofuran (2.0 ml), add thionyl chloride (〇.〇56ml) 'N,N-dimethylformamidine The amine (1 drop) was stirred at 55 ° C for 3.5 hours, and the reaction mixture was concentrated to give 3-methylsulfonylbenzoic acid chloride. (2) Tetrahydrofuran of 1-({[ 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (10 mg, 0.320 mmol) In a solution of 2.0 ml), a solution of 3-ethylsulfonylbenzoic acid chloride in tetrahydrofuran (2. 〇rnl) obtained by adding triethylamine (〇.〇89 ml), (1)-202-200918053 The mixture was stirred at room temperature for 18 hours, and the reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate. After extraction with ethyl acetate, the mixture was washed with aq. After filtration and concentration, the obtained residue was purified by silica gel column chromatography (purified, solvent, ethyl acetate) to give a pale brown amorphous 1-[({5-[4_( ( [3-(Methylsulfonyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (1 5 6 mg ) 〇 (Example 63) According to the production method of Example 62, by using 1-({ 〔5-(4-aminophenyl)azypdin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (reference synthesis) Example 3-1), or change to Using 1-( { 〔5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (Reference Synthesis Example 3-2), 1- ( { [ 5- (4-Aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Reference Synthesis Example 3-7) ' 1- ( { ( 5- (4-amino-3) -fluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Reference Synthesis Example 3-13), 1-( {[ 5-(4-Aminophenyl)pyrimidine- 2-methyl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (synthesized according to the production method of Reference Synthesis Example 3-6), 3 - { 〔5-(4-aminophenyl)pyrimidine-2-yl Oxy} 2,2-dimethylpropionic acid methyl ester (synthesized according to the method of Example 2); using 2,4-dimethylbenzoic acid or replacing with 2,5-dimethyl Benzoic acid, -203- 200918053 biphenyl-3-carboxylic acid, 3,5-dimethylbenzoic acid, 2,6-dimethylbenzoic acid, 3-fluoro-4-methoxybenzoic acid, 3-methyl Oxy-4-methylbenzoic acid, 3-chloro-4-methoxybenzoic acid, 4-chloro-3-methylbenzoic acid, 5,6,7,8-tetrahydronaphthalene-2-carboxylic acid, 3-(ethenyloxy)benzoic acid, 3-(propan-2-yl)benzoic acid, 3- ( Methylsulfanyl)benzoic acid, 4-chloro-3-(trifluoromethyl)benzoic acid, 3-cyanobenzoic acid, or 3-chloro-4-methylbenzoic acid gave the following compound of the present invention. 1-( { 〔5-(4-{ 〔(2,4-Dimethylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 1 8 3 ) 1-( { 〔5-(4-丨[(2,5-Dimethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxanylmethyl) ring Methyl butanecarboxylate (Compound No. 184) 1- { 〔( 5- { 4-[(Biphenyl-3-ylcarbonyl)amino]phenyl}pyridine-2-yl)oxy]methylindole ring Methyl butanecarboxylate (Compound No. 1 8 5 ) 1-( { 〔5-(4-{ 〔(3,5-Dimethylphenyl)carbonyl)amino}phenyl)pyridin-2-yl Oxymethyl}cyclo)cyclobutanecarboxylic acid methyl ester (Compound-204-200918053 No. 186) 1-( { [--(4-(((2,6-methylphenyl)))] Methyl}pyridin-2-yloxy]methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 187) 1-( { 〔5-(4-{ 〔 (3 - gas-4 - methoxy) Phenyl)amino]phenyl)pyridine-2- Oxy]methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 1 8 8 ) 1-( { 〔5-(4-{ 〔(3-methoxy-4-methylphenyl)carbonyl)amine Methyl phenyl)pyridin-2-yloxymethyl}cyclobutanecarboxylate (Compound No. 1 8 9 ) 1-( { 〔5-(4-{ 〔 (3-chloro-4- Methoxyphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 1 9 0 ) 1-( { 〔5-(4-丨[(4-Chloro-3-methylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 1 9 1 ) 1- { 〔(5-{4-[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid Base ester (Compound No. 192) Bu [({5-[4-({[3-(Ethyloxy)phenyl)carbonyl)amino)phenyl]pyridin-2-yl}oxy)methyl]) Methyl butanecarboxylate (Compound No. 1 9 3 ) 1-[({5-[4-( { [3-(Pron-2-yl)phenyl)]]]amino)phenyl] Methyl pyridine-2-yl}oxy)methyl]cyclobutanecarboxylate (combination-205-200918053) 9 4 ) ^[ ( { 5_[ 4_ ( { 〔 3_ (Methylsulfanyl)phenyl)carbonylguanidino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl Ester (Compound No. 195) Bu [(丨5_[ 4_ ( { -4-chloro-3-(trifluoromethyl)phenyl)indolyl)amino)phenyl]«-2-yl}oxy)methyl 〕 环丁院 residual acid methyl vinegar (comp. No. 196) b ( { 〔 5_ ( 4_ { 〔(3-cyanophenyl)carbonyl)amino}phenyl) pyridine _ 2 -yloxy}methyl) Methyl cyclobutanecarboxylate (Compound 5 5 197) Bu (丨[5-(4-{[(3,5-dimethylphenyl)carbonyl]amino}}yl)pyridin-2-yl Oxymethyl}cyclo)propanecarboxylic acid methyl ester (Compound No. 198) 1_{ [(5- {4-[(5,6,7,8-tetrahydronaphthalen-2-yl)amino) Benzo}pyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid methyl ester (Compound No. 199) 1-[({5-[4_( { [3-(propyl)-2-yl)phenyl) Ore-based guanidino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid methyl vinegar (Compound No. 2 0 0 ) 1-( { 〔5-(4-{ 〔 (3 - Chloro-4-methoxyphenyl) Amino} phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (Compound No. 2 0 1 ) 1 - ( { 〔5-(4-{[(3,5-dimethyl) Methylphenyl)amino]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound-206-200918053 No. 202) 1_{[(5-{4 -[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyrimidin-2-yl)oxy]methylindolecyclobutane residual acid methyl ester (Compound No. 203) 1-[({5-[4-({[3-(propyl-2-yl))yl]carbyl}amino)phenyl]pyrimidin-2-ylindoleoxy)methyl]cyclobutanthine Acid methyl vinegar (compound No. 204) 卜(丨[5_(4-{ 〔(3-chloromethoxyphenyl)indolyl)amino}phenyl)pyrimidin-2-yloxy}methyl) ring Methyl butanecarboxylate (Compound No. 2 0 5 ) Bu({[ 5_ ( 4· {[(3-chloro-4-methylphenyl)carbonyl]amino}-3-fluorophenyl)pyrimidine- 2-yl]oxy)methyl)cyclobutanyl decanoic acid methyl vinegar (Compound No. 2 0 6 ) ^({[,(^{[(^-dimethylphenyl hydrazinocarbonyl fluorenyl phenyl)) Pyrimidine-2-yloxymethyl}methyl) Base vinegar (Compound No. 207) 卜{ [(5· { 4_[( 5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyrimidin-2-yl)oxy]methyl丨 丙 院 残 残 残 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 ( ( ( ( ( ( ( ( 2-(yl)}oxy)methyl]cyclopropene acetophenone methyl vinegar (Compound No. 2 0 9 ) b ( { 〔 5_ ( 4_ { 〔( 3-Chloro-4-methoxyphenyl)carbonyl)amine Methyl} phenyl)pyrimidin-2-yloxyxanthylmethyl)cyclopropanone residual methyl vinegar (compound-207- 200918053 No. 2 1 0 ) 3·{ 〔5·(4·{ 〔 (3- Chloro-4-methylphenyl)carbonyl]amino}phenyl)pyrimidinyl]oxanthene-2,2-dimethylpropanoic acid methyl ester (Compound No. 2 11) (Example 64) Synthesis of methyl 5-(4_{ 〔(3-chlorophenyl)aminocarbamimidino)}phenyl)pyrimidine-2-yloxy}methyl)cyclobutanecarboxylate (Compound No. 212 Manufacturing (化104)

a solution of methyl phenyl)pyrimidin-2-yloxy]methyl)cyclobutanecarboxylate (0.15 0 g, 0 · 3 1 4 mm ο 1 ) in chloroform (3 m 1 ) Diethylamine (〇_〇 66 ml, 〇.47 mmol) and 3-chloroaniline (〇_〇 39 ml, 0.38 mmol) were added thereto, and the mixture was stirred at 60 ° C for 5 hours, and the reaction solution was cooled to room temperature to react. The liquid was diluted with ethyl acetate, and the organic layer was washed with a saturated aqueous solution of ammonium chloride and saturated aqueous sodium hydrogen carbonate and brine, and then dried over anhydrous magnesium sulfate. The filtrate was concentrated, and the obtained residue was subjected to chromatography on silica gel column (ethyl acetate:hexane = 1:1 to ethyl acetate:methanol = 10:1) 5 to 1: 0) Purification to give a pale yellow amorphous crystal of 1-({[-(4-{[[3-chlorophenyl)aminomethylindolyl]}}-phenyl-208-200918053) Pyrimidine-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (〇.123g) (Example 165) According to the production method of Example 64, by using 1-( { 〔5-(4 -{ 〔(4-Nitrophenoxy)carbonyl) Methyl phenyl)pyrimidin-2-yloxymethyl}cyclobutanecarboxylate (refer to Synthesis Example 4-4), or replaced with 1-( { 〔 5-( 3-fluoro-4) - {[(4-Nitrophenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Reference Synthesis Examples 4 - 3), 1- ({[5-(4-{[(4-Nitrophenoxy)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (Reference Synthesis Example 4 -2 ), or 1-( { 〔5-(4-{ 〔(4-nitrophenoxy)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Methyl ester (refer to Synthesis Example 4-1); use 3-chloroaniline or replace with 2-chloro-4-fluoroaniline, 2-chloro-5-fluoroaniline, 2-fluoro-5-(trifluoromethyl) Aniline, 2-fluoro-5-methylaniline, 2-chloro-4-fluoro-5-methylaniline, 3-chloro-4-fluoroaniline, 3-chloro-2-fluoroaniline, -209- 200918053 4-methyl-3-(trifluoromethyl)aniline, 4-fluoro-3-(trifluoromethyl)aniline, 4-chloro-3-methoxyaniline, 3-chloro-4-methoxyaniline , 3-(propan-2-yl)aniline, 4-fluoro-2-(trifluoromethyl)aniline, 2 - 5- 5-(trifluoromethyl)aniline, 4-fluoro-3-methylaniline, 2-bromo-5-methylaniline, 3-(trifluoromethyl)aniline, or 4-chloro-3-( Trifluoromethyl)aniline gives the following compound of the invention 〇1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethylindenyl)amino} -3-fluoro Phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 1 3 ) 1-( { 〔5-(4-{ 〔 (2-Chloro-5-fluorobenzene) Methylaminomethylamino]amino}-3-fluorophenyl)pyrimidin-2-yloxyxyl}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 1 4 ) 1-[ ( {5 -[3-Fluoro 4-({[2-fluoro-5-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclo Butanecarboxylic acid methyl ester (Compound No. 2 15) 1-( { [---3-fluoro-4-{[(2-fluoro-5-methylphenyl)aminomethylindenyl]amine }Phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 1 6 ) -210- 200918053 Bu ({ 〔5-(4_{ 〔 (2-Chloro-4) -Fluoro-5-methylphenyl)aminomethylindenyl]amino}phenyl)«.2·yl]oxanylmethyl)cyclobutane (tetra) acid Base vinegar (Compound No. 2 1 7 ) Bu (丨[5_(4_丨[(2_Chloro-4-phenylphenyl)aminomethylindolyl]amino}phenyl)« -2-yl]oxy} Methyl) Cyclobutylidene Residual Methyl Vinegar (Compound No. 2 1 8 ) { 〔5_(4_{ 〔(3_Chloro-4-Phenylphenyl)Aminocarbamic Acid]Amino}Phenyl)pyrimidine-2 -yl}oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 1 9 ) ^ (丨[5_( 4_丨[(2_Fluoro-5-methylphenyl)aminocarbinyl) Amino phenyl)pyrimidin-2-yloxy}methyl)cyclobutyl carboxylic acid methyl ester (compound No. 2 2 0 ) 1-( { 〔5-(4-{ 〔 (3 - chloro- 2-fluorophenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yloxy}methyl)cyclobutane residual acid methyl ester (Compound No. 2 2 1 ) 1-[ ( {5 -[4-( { 〔4-methyl-3-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopentene Acid methyl ester (Compound No. 222) 1-[({5-[4-( { 〔4-fluoro-3-(trifluoromethyl)phenyl))amino]yl}amino)phenyl]pyran Steep-2_yloxymethyl)methyl]cyclobutanic acid methyl ester No. 223) 1_(丨[5-(4-{ 〔(4-chloro-3-methoxyphenyl)aminomethyl) ylamino phenyl)pyrimidin-2-yl]oxyindole methyl Cyclobutanecarboxylic acid methyl ester (Compound No. 2 2 4 ) -211 - 200918053 1-( { 〔5-(4-{ 〔(3-Chloro-4-methoxyphenyl)aminomethyl fluorenyl Amino}phenyl)pyrimidin-2-yloxyxyl}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 225) 1-[({5-[4-( { [3-(propane-2) -yl)phenyl]aminocarbamimidyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 226) 1-[ ( {5-[ 4-( { 〔4-fluoro-2-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl Ester (Compound No. 227) 1_[({5-[4-( { 〔2-fluoro-5-(trifluoromethyl)phenyl)aminocarboxamyl}amino)phenyl]pyrimidin-2-yl }Oxy)methyl]cyclobutanecarboxylic acid methyl ester (compound number) 1-[({5-(4-( { 〔2-methyl-5-(trifluoromethyl)phenyl))) Mercapto}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid Base ester (Compound No. 229) 1-( { 〔5-(4-{ 〔(2-Chloro-5-fluorophenyl)aminomethylindenyl)amino}phenyl)pyrimidin-2-yl]oxy} Methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 23 0 ) 1-( { 〔5-(4-{ 〔(4-Chloro-3·methoxyphenyl)aminomethylindenyl) Amino Phenyl)pyrimidine-2-yloxy}methyl)cyclopropanecarboxylic acid methyl ester (Compound No. 2 3 1 ) ' 1-( { 〔5-(4-{ 〔(3-Chlorophenyl)amine Methylmercapto]amino}phenyl)pyrimidin-2-yl]oxo}methyl)cyclopropanecarboxylic acid methyl ester (Compound No. 2 3 2 ) -212- 200918053 1- ( { [ 5- ( 4- { 〔(3-Chloro-amino}phenyl)pyrimidin-2-yloxy compound No. 2 3 3 ) 1- ( { 〔 5- ( 4- { 〔 (3-chloro· }phenyl)pyrimidine-2 -yl]oxy}methane number 2 3 4 ) 1-( { 〔 5-(4-{ 〔(2-fluoro- phenylphenyl)pyrimidin-2-yloxy} compound number 2 3 5 ) 1 - 〔( { 5- 〔 4-( { 〔4-Fluoro-indenyl)amino)phenyl]pyrimidin-2-yl ester (Compound No. 23 6 ) 1- 〔 ( { 5- 〔 4- ( { 〔 4-fluoro-indenyl}amino)phenyl]pyrimidin-2-yl ester (Compound No. 23 7) 1-[({ 5-[4-({[2-Fluoro-indenyl)amino)phenyl]pyrimidin-2-yl ester (Compound No. 23 8 ) 1- ( { [ 5- ( 4- { 〔(4-Fluoro-yl}phenyl)pyridin-2-yloxy} Compound No. 2 4 0 ) 1- ( { 〔 5 - ( 4 - { 〔 ( 2 -Bromo-yl}phenyl)pyridine -2 -yloxy} Compound No. 2 4 1 ) 4-Methoxyphenyl)aminocarbamimidyl] }methyl)cyclopropanecarboxylic acid methyl ester (4-fluorophenyl)aminocarbamidine Methylamino)cyclopropanecarboxylic acid methyl ester (5-methylphenyl)aminomethylindenyl]amine methyl)cyclopropanecarboxylic acid methyl ester (3-(trifluoromethyl)benzene 5-aminomethyl}oxy)methyl]cyclopropanecarboxylic acid methyl 2-(trifluoromethyl)phenyl]aminomethyl}oxy)methyl]cyclopropanecarboxylic acid methyl 5-(trifluoromethyl Phenyl]aminomethylamino}oxy)methyl]cyclopropanecarboxylic acid methyl 3-methylphenyl)aminomethylindenyl]amine methyl)cyclobutanecarboxylic acid methyl ester (5-methyl Phenyl)aminomethylmercapto]aminemethyl)cyclobutanecarboxylic acid methyl ester (Chemical-213-200918053 1-( { 〔5-(4-{ 〔 (2 - chloro-4-fluoro-5-) Methylphenyl)aminomethylmercapto]amine }Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 242) 1-[({5-[4-( { [3-(Trifluoromethyl))benzene Methylaminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 243) 1-[ ( {5-[4-( { [4-Chloro-3-(trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (compound number 244 ) 1-( { 〔5-(4-{ 〔(2-Fluoro-5-methylphenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]oxy}methyl) Methyl butanecarboxylate (Compound No. 2 4 5 ) (Example 66) 1-[({5-[4-( { [4-Chloro-2-(trifluoromethyl)phenyl]]amino) Synthesis of fluorenyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 246)

1-({[5-(4-Aminophenyl)pyridin-2-yl]oxy}methyl)-214- 200918053 chloroform methyl phthalate (〇.326g, L〇4mmo1) chloroform (6) In the solution, pyridine (0 1 2 6 m 1 , 1 · 5 6 mm 0 1 ) formic acid 4-nitrophenyl (〇·231§, i.150111101) was added under ice cooling. Triethylamine (0 · 218 m 1 , 1 5 6 mm 01 4 -chloro-2-(trifluoromethyl)aniline (〇_17〇m1, 5 °C stirring for 4.5 hours) was added to the reaction under ice cooling. The liquid was cooled to room temperature and diluted with acid water. The organic layer was washed with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium carbonate and brine. The organic layer was dried over anhydrous magnesium and filtered. The filtrate was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography ( NH EtOAc, ethyl acetate: hexanes: 2) to afford crude 1-[(5-[4- ( 2-(Trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenylpyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester, the obtained suspension was suspended in acetic acid Ethyl ester (2ml), diisopropyl ether (10ml), After dissolving, it was cooled to room temperature, and the resulting crystal was filtered off and washed with propyl ether to give a colorless solid of 1-[(5-[4-(4-chloro-2-(trifluoro)) Phenyl]amino]aminomethylindenyl}amino)phenylpyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (〇.161g). (Example 67) According to Example 66 a method for producing by using 1-({[5-(4-aminophenyl)pyridine-2-yl]oxy})cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-1), or 1- 1-(丨[5-(4-Amino-3-fluorophenyl)pyridin-2-yl]oxy}methyl ml) and chlorine mixed 1) and the ester and acid hydrogen sulfate obtained hospital=1 [4-]pyrazole solid 70 °C diiso{[]pyridylmethyl)cyclo-215- 200918053 butanecarboxylic acid methyl ester (refer to Synthesis Example 3-12), 1-( { [5-(4) -amino-2-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-9), 1-( { [5-(4-amino group) -2- gas radical) D ratio D疋-2-yl]oxy}methyl) methyl butyl sulfonate (refer to Synthesis Example 3-10), 1- ( { 〔 5- ( 4-amine 2-methylphenyl)pyridin-2-yl]oxy }methyl) cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-11), 1-( { [ 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylate Acid ethyl ester (refer to Synthesis Example 3-3), 1-({[ 5-(4-aminophenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid methyl ester (Reference Synthesis Example) 3-2 ), 1-( { 〔5-(4·-amine basic) D is 卩疋-2-yl)oxy}methyl) cyclopentancarboxylic acid methyl ester (Refer to Synthesis Example 3-4) , 1-( { [ 5-(4-Aminophenyl) fluorene than U-den-2-yl]oxy}methyl) cyclohexyl carboxylate (refer to Synthesis Example 3-5), 1-( {[ 5-(4-Aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Reference Synthesis Example 3-7), 1-( {[ 5-(4- Ethylphenyl)pyrimidin-2-yl]oxo}methyl)cyclopropanecarboxylic acid ethyl ester (refer to Synthesis Example 3-6), or 1-({[ 5-(4-aminophenyl)pyrimidine- 2-methyl]oxy}methyl)cyclopentanecarboxylic acid methyl ester (refer to Synthesis Example 3-8), Bu ({[5-(4-Amino-2,5-difluorophenyl)pyridine-2) -yl)oxy}methyl)cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3 -1 4 ), or 1 - ( { 〔5 - (4. Amino-3) ,5-difluorophenyl)pyrimidin-2-yloxy}methyl)cyclobutanecarboxy-216- 200918053 acid methyl ester (refer to Synthesis Example 3-15); using 4-chloro-2-(trifluoro) Methyl)aniline, or substituted for 3-methylaniline, 3-(trifluoromethoxy)aniline, 2-chloro-4-(trifluoromethoxy)aniline, 2-methyl-4-(three Fluoromethoxy)aniline, 2-fluoro-5-(trifluoromethyl)aniline, 3-chloroaniline, 3,5-dichloroaniline, 3-chloro-4-methoxyaniline, 4-amino- 3-methylbenzonitrile, 3-chloro-2-fluoroaniline, 4-tert-butylaniline, 2-methyl-5-(trifluoromethyl)aniline, 3-(propan-2-yl)aniline, 4-chloro-3-methoxyaniline, 2,2-difluoro-1,3-benzodioxan-5-amine, 4-methyl-3-(trifluoromethyl)aniline, 2-chloro -5·(trifluoromethyl)aniline, 4-amino-2-(trifluoromethyl)benzonitrile, 2-chloro-4-fluoroaniline, 5-chloro-2-fluoroaniline, 2-chloro-5 -Fluoroaniline, 2-fluoro-5-methylaniline, -217- 200918053 4-fluoro-2-(trifluoromethyl)aniline, 2-chloro-4-(trifluoromethyl)aniline, 4-fluoro- 3-(trifluoromethyl)aniline, 2-(trifluoromethoxy)aniline, 3-chloro-4-fluoroaniline, cyclohexaneamine, or 2 4-Dimethylaniline gave the following compounds of the invention.卜({[5-(4-{ 〔(3-methylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 4 7 ) 1-[({5-[4-( { [3-(Trifluoromethoxy)phenyl]aminomethylmethyl}amino)phenyl]pyridin-2-yl} Oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 2 4 8 ) 1-[ ( {5-[4-( { [2-chloro-4-(trifluoromethoxy)phenyl]amine) Methylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 249) Bu [({5-[4-( { [2- 4- 4-(Trifluoromethoxy)phenyl]aminomethylindenyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 2 5 0) 1-[({5-[4-( { [2-fluoro-5-(trifluoromethyl)phenyl]aminomethylindenyl)amino)phenyl]pyridin-2-yl}oxy) Methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 251) 卜({ 〔5-(4-{ 〔(3-Chlorophenyl)aminomethylindenyl)amino}benzene-218- 200918053 base) Pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (combination Item No. 252) 1-({[5-(4-{[(3,5-Dichlorophenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl) ring Methyl butanecarboxylate (Compound No. 2 5 3 ) Bu ({ [ 5-(4-{[[3-chloro-4-methoxyphenyl)aminomethylindenyl]amino}phenyl) Methylpyridin-2-yloxymethyl)cyclobutanecarboxylate (Compound No. 2 5 4 ) 1-( { 〔5-(4-{ 〔(4-Cyano-2-methylbenzene) Aminomethylaminomethyl]amino}phenyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 25 5 ) 1-( { 〔5-(4-{ [(3-Chloro-2-fluorophenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 256) 1- ( { [ 5-(4-{ 〔(4-tert-butylphenyl)aminocarbamimidyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl Ester (Compound No. 2W) 1-[({5-[4-( { [2-methyl-5-(trifluoromethyl)phenyl]aminocarbamoyl)amino)phenyl]pyridine-2 -yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 2 5 8 ) 1-[ {5-[4-( { 〔3-(propyl-2-yl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid Methyl ester (Compound No. 2 5 9 ) 1-( { 〔5-(4-{ 〔(4-Chloro-3-methoxyphenyl)aminocarbinyl) -219- 200918053 Amino}Phenyl Pyridin-2-yloxyoxomethyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 6 0 ) 1-({[5-(4-{[(2,2-Difluoro-1,3) - benzodioxan-5-yl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 6 1 ) 1 -[({5-[4-( { [4-methyl-3-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl 】 Cyclobutanecarboxylic acid methyl ester (Compound No. 262) 1-[({5-[4-( { 〔2-chloro-5-(trifluoromethyl)phenyl)aminomethyl hydrazino) Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 263) 1-[({5-[4-( { [4-Cyano-3-(3) Fluoromethyl)phenyl]aminomethylmethyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid Base ester (Compound No. 264) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]oxy} Methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 6 5 ) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amine} 3-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 6 6 ) 1-( { 〔5-(4-{ 〔 (2-Chloro- 4-fluorophenyl)aminomethylindenyl]amino}-2-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 2 6 7 ) 1- ({[5-(2-Chloro-4-{[(2-chloro-4-fluorophenyl)aminocarbinyl]-220- 200918053 Amino}phenyl)pyridin-2-yl]oxy}A Methyl cyclobutanecarboxylic acid methyl ester (compound No. 2 6 8 ) 1_( { 〔5-(4-{ 〔(2- gas-4-oxo)aminocarbamic acid) amine group -2- Methylphenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 269) 1-( { 〔5-(4-{ 〔 (5-Chloro-2-fluorobenzene) Methylaminomethylamino]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (combination No. 2 7 0 ) 1-( { 〔5-(4-{ 〔(2-Chloro-5-gas-based)Aminomethyl]amino}phenyl)pyridin-2-yl]oxy}methyl ) Cyclobutanecarboxylic acid methyl ester (Compound No. 2 7 1 ) 1-( { 〔5-(4-{ 〔(2 -Ga-5--phenylphenyl)aminoglycolyl)amino} -3 -Fluorophenyl)pyridin-2-yloxyoxomethyl)cyclobutanecarboxylic acid methyl ester (Compound No. 272) 1-[({5-[3-Fluoro-4-({[2-fluoro-) 5-(Trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 273) 1-( { 〔5-(3 -Gas-4-{[(2-But-5-methylbenzyl)aminomethyl]amino}phenyl) phenoxy-2-yloxy}methyl)cyclobutane Methyl vinegar (Compound No. 2 7 4 ) 1-( { 〔5-(4-{ 〔(2-Chloro-5-perphenyl)aminomethyl]amino}-2-fluorobenzene Methyl)pyridin-2-yloxy]methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 275) 1-[({5-[2-Fluoro 4-({[2-fluoro- 5-() Trifluoromethyl)phenyl]amine-221 - 200918053 methylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate Acid methyl ester (Compound No. 276) { 〔5-(2-Chloro-4-{[(2- gas-5-perphenyl)aminomethyl]amino}phenyl)pyridin-2-yl Oxymethyl}cyclo)cyclobutanecarboxylic acid methyl ester (Compound No. 277) 1-[({5-[2-chloro-4-( { [2-fluoro-5-(trifluoromethyl)phenyl) Aminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 278) 1-[ ( {5-[4-( { 〔 4-fluoro-2-(trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid ethyl ester (Compound No. 279) 1-[({5-[4-({[4-Chloro-2-(trifluoromethyl)phenyl]aminomethyl)amino)phenyl]pyridin-2-yl}oxy)methyl Ethyl cyclopropanecarboxylate (Compound No. 280) 1-[({5-[4-( { 〔2-chloro-4-(trifluoromethyl)phenyl)aminocarbamoyl}amino) Phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid ethyl ester (Compound No. 2 8 1 ) 1-[ ( {5-[4-( { 〔4-fluoro-3-(trifluoro) Methyl)phenyl]aminomethylindenyl}amino)phenyl]pyridin-2-yl}oxy) Ethyl cyclopropanecarboxylate (Compound No. 282) 1-[({5-[4-( { 〔2-(Dimethylmethyl)phenyl]amino]yl}}amino)phenyl Ethyl pyridin-2-yl}oxy)methyl]cyclopropanecarboxylate (Compound No. 2 8 3 ) 1-( { 〔5-(4-{ 〔(3 -Chloro-4-phenylphenyl)amine Amino-thiol-222- 200918053 }Phenyl)pyridin-2-yloxy}methyl)cyclopropanecarboxylate Ethyl ester (Compound No. 2 8 4 ) 1-[ ( {5·[4- ({[2-Chloro-4-(dichloromethoxy)benyl]urephetyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropane residual acid ethyl ester (Compound No. 2 8 5 ) 1-[({5-[4-( { 〔2-Methyl-4-(dimethoxy)))]]]]]] Ethyl pyridin-2-yl}oxy)methyl]cyclopropanecarboxylate (Compound No. 286) 1-[({5-[4-( { [3-(Trifluoromethoxy)phenyl])amino) Methyl hydrazide}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid ethyl ester (Compound No. 287) 1- { 〔 ( 5- { 4-[(cyclohexylamino) Amidino)phenyl] Ethyl-2-yl)oxy]methyl}cyclopropanecarboxylate (Compound No. 288) 1-[({5-[4-( { [2-fluoro-5-(trifluoromethyl)phenyl) Aminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid methyl ester (Compound No. 289) 1- ( { 〔 5- ( 4- { 〔 2 -Chloro-4-fluorophenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid methyl ester (combination _ material number 290) { 〔5 -(4-{ 〔(2-oxo-5-methylphenyl)aminomethyl carbyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid methyl vinegar ( {匕合编号号 No. 2 9 1 ) 1-({[5-(4-{[(2,4-Dimethylphenyl)aminocarbamoyl]]- --223- 200918053 }}phenyl)pyridine Ethyl-2-yloxy]methyl)cyclohexanecarboxylate (Compound No. 2 9 2 ) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)amino Methylamino]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclohexanecarboxylic acid ethyl ester (Compound No. 2 9 3 ) 1-[ ( {5-[4-( { 〔3 -(trifluoromethoxy)phenyl]aminocarboxamido}amino)phenyl]pyrimidin-2-yl} Methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 294) 1-[({5-[4-({[[3-(Trifluoromethoxy)phenyl]aminomethyl)amino) Ethylphenylpyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid ethyl ester (Compound No. 295) 1-[({5-[4-( { [2-methyl-4-(trifluoro]) Methoxy)phenyl]aminomethylmethyl}amino)phenyl]pyrimidin-2-ylindoleoxy)methyl]cyclopropanecarboxylic acid ethyl ester (Compound No. 296) 1-[ ( {5-[ 4-( { 〔2-Chloro-4-(trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid ethyl Ester (Compound No. 297) 1-[({5-[4-( { [2-(Trifluoromethoxy)phenyl]aminocarbamimidino)phenyl]pyrimidin-2-yl}oxy )methyl]cyclopropane residual acid ethyl ester (Compound No. 298) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amino}benzene Ethyl pyrimidin-2-yloxy}methyl)cyclopropanecarboxylic acid ethyl ester (Compound No. 2 9 9 ) 1-( { 〔5-(4-{ 〔 (2-Chlor-4-phenylphenyl) Aminomethylmercapto]amino-224- 200918053 }benzene Pyrimidine-2-yloxy}methyl)cyclopentanecarboxylic acid methyl ester (Compound No. 3 0 0 ) 1-( { 〔5-(4-{ 〔 (2-Fluoro-5-methylphenyl) Aminomethylamino]amino}phenyl)pyrimidin-2-yl]oxanylmethyl)cyclopentanecarboxylic acid methyl ester (Compound No. 3 0 1 ) 1-( { 〔5-(4-{ [(2-Chloro-4-fluorophenyl)aminomethylindolyl]amino}-2,5-difluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 546) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amino} -3,5-difluorophenyl)pyrimidine-2 -yl}oxy}methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 547) (Example 6 8) 1-( { 〔5-(4-{[(2,5-Dichlorophenyl)amine Manufacture of methylmeridino]amino}phenyl)pyridin-2-yloxy]methyl)cyclobutanecarboxylic acid methyl ester (Compound No. 3 0 2 ) [Chem. 106]

1 - ({[5-(4-Aminophenyl)pyridin-2-yl]oxyindolemethyl)cyclobutanecarboxylic acid methyl ester (0 · 5 0 1 g, 1 · 6 1 mm ο 1 Add 2,5-dichlorophenylisocyanate (〇.363g, 1.93mmol) in a solution of tetrahydrofuran (5ml). Stir at room temperature for 1 7.5 hours, and dilute the reaction mixture with ethyl acetate. The organic layer was washed with anhydrous sodium sulfate-225-200918053 water, and the solid obtained by filtration of the desiccant 'concentrated filtrate under reduced pressure was suspended in ethyl acetate' to obtain a colorless solid. 1-({[ 5-(4-{[(2,5-monochlorophenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Methyl ester (〇.631g) (Example 69) According to the production method of Example 68, by using 1-({[5-(4-aminophenyl)pyridin-2-yloxy}methyl) Ethyl cyclopropanecarboxylate (refer to Synthesis Example 3-3) or ethyl 1-({[ 5-(4-aminophenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylate (Refer to Synthesis Example 3 _6), Substituting 1-( { 〔5·(4-Aminophenyl)pyridin-2-yl Oxymethyl}cyclobutanecarboxylic acid methyl ester (refer to Synthesis Example 3-1), using 4_(trifluoromethoxy)phenylisocyanate in place of 2,5-dichlorophenyl isocyanate, the following Inventive compound. ({5-[4-({[4-(Dimethoxymethoxy)phenyl]amino)carboxylic acid}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid ethyl Ester (Compound No. 3 0 3 ) 1-[({5-[4-( { [4-(Trifluoromethoxy)phenyl]aminocarbamoyl)amino)phenyl]pyrimidin-2-yl }Oxy)methyl]cyclopropanecarboxylic acid ethyl ester (Compound No. 2 3 9 ) (Example 70) { 〔5-(4-{ 〔(4-Fluorophenyl)Ethyl)amino}phenyl -226- 200918053 pyridine-2-yloxymethyl)cyclobutanecarboxylic acid (Compound No. 30 4 ) Manufactured (Chemical Formula 1 〇 7)

1-( { 〔5-(4-{ 〔(4-Fluorophenyl)ethinyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid methyl ester ( A mixed solution of the compound No. 139) (130 mg, 0.290 mmol) in tetrahydrofuran (2.6 ml) and methanol (2.6 ml) was added to a 6M aqueous sodium hydroxide solution (2 ml), and the mixture was stirred at room temperature for 20 hours, and then added to the reaction mixture. The mixture was neutralized with hydrochloric acid, diluted with ethyl acetate, extracted with ethyl acetate, and then washed with water, saturated aqueous sodium hydrogen carbonate and brine, dried (MgSO. The obtained residue was recrystallized (ethyl acetate-hexane) to give a pale brown powder of 1 - ( { s s s s Pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid (95 mg). (Example 7 1 ) According to the production method of Example 70, the compound of the present invention of Compound Nos. 1 04 to 138 and 140 to 211 was used as a substituted ({[%(4-{[[4-fluorophenyl)]). Ethyl mercapto]amino phenyl)pyridine-2-yloxy}methyl)cyclobutanyl residue methyl vinegar (Compound No. 139), which is a compound of the present invention in an amount of 3 sec or less.丨[5_(4-{ 〔(4-Fluoro-3-methylphenyl)carbonyl)amino benzene-227- 200918053 yl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (compound) No. 305 ) 1-( { 〔5-(4-{ 〔(3 - 钟! -4 -methyl-yl))]]]]}}}}}]]pyridin-2-yl]oxy}methyl)cyclobutane Carboxylic acid (Compound No. 306) 1_[({5-[4-( { 〔4 - Mirror(-3-(di-methyl)phenyl))}amino)phenyl]pyridin-2-yl} Oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 0 7 ) 1-[({5-[4-( { [2-methoxy-4-(trifluoromethyl)phenyl]carbonyl)amine Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 0 8 ) 1-( { 〔5-(4-{ 〔 ( 3,5- - 藏本基 ) ) Amino}phenyl)pyridin-2-yloxymethyl}cyclobutanecarboxylic acid (Compound No. 3 09 ) 1- ( { [ 5- ( 4- { 〔 (2,2-difluoro-) 1,3 -benzodioxan-5-yl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (compound No. 3 1 0 ) 1- [ ( { 5-[4-( { 〔2-methoxy-3-(trifluoromethyl)phenyl)carbonyl}amino)phenyl] Pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound No. 3 1 1 ) 1-( { 〔5-(4-{ 〔 (2,3 - —••)) Benzyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 1 2 ) 1- [ ( { 5- [ 4- ( { [2-methoxy- 5- ( Trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 1 3 ) -228- 200918053 l-[ ( {5- [4-( { 〔3-(Trifluoromethoxy)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 1 4 ) 1 -({[5-(4-{[(2-chloro-4,5-indolyl)-yl)]phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate Acid (Compound No. 3 15) 1-( { 〔5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl) Cyclobutanecarboxylic acid (Compound No. 3 16 ) 1-( { [5-(4-([3-Fluorophenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl) Cyclobutanecarboxylic acid (Compound No. 317) 1-[ ( {5-[4-( { 〔3-(1,1,2,2-tetrafluoroethyl) Phenyl]carbonyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound No. 3 1 8 ) 1-( { 〔5-(4-{ [ ( 3 4-(methoxyphenyl)indenyl]amino}phenyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 19) 1-( { 〔5-(4 -{[(4-Methoxy-3-methylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 20 ) 1-(丨[5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl]aminoindole-3-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid ( Compound No. 32 1) Bu({ 〔5-(4-{ 〔(3,4-diethylphenyl)carbonyl)amino}benzene-229- 200918053 yl)pyridin-2-yloxy}methyl) Cyclobutanecarboxylic acid (Compound No. 322) 1-( { 〔5-(4-{ 〔(4-chloro-3- per benzyl) ortho}amino}phenyl)pyridin-2-yl]oxy} Methyl)cyclobutanecarboxylic acid (Compound No. 323) 1-[({5-[4-({[3-fluoro-4-(trifluoromethyl)phenyl)carbonyl)]amino)phenyl]pyridine -2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound number 3 2 4 ) 1 ( { [5-(4-{ 〔(3-Gas-based) ortho)amino]yl)D-pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 25 ) ({5-[4-( { 〔3-(Trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 26 1-[({5-[4-({[4-fluoro-2-(trifluoromethyl)phenyl)carbonyl)]amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutane Alkanecarboxylic acid (Compound No. 3 2 7 ) 1-( { 〔5-(4-{ 〔(3,5-Dichlorophenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl Cyclobutanecarboxylic acid (Compound No. 328) 1-( { 〔5-(4-{[(2,5-Difluorophenyl)carbonyl]amino phenyl)pyridin-2-yl]oxy} A Cyclobutanecarboxylic acid (Compound No. 3 29 ) 1-( { 〔5-(4-{ 〔(4-T--2-methoxyphenyl)cyclo)amino}phenyl)pyridine-2 -yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 3 0 ) 1-( { 〔5-(4-{ 〔(3,4-Difluorophenyl)carbonyl)amino}phenyl) Pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 33 1 ) -230- 200918053 ί4_( { [4-(Trifluoromethoxy)phenyl]carbonyl}amine

1 -[ C { 3 - L ...?丨Μ 甲 甲 1 1 1 竣 竣 竣 竣 竣 化合物 化合物 化合物 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Oxyphenyl)carbonyl]amino]p-phenyl)pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 333) Γ4_{[(3-Methylphenyl)carbonyl]aminopurine Phenyl) 1 _ ( { L 5 1 pyridin-2-yl)oxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 3 4 ) 1 [(丨5_[2_氟_4-( { 〔3- (trifluoromethyl)benzyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound No. 3 3 5 ) 1 [ ( {5_[3-gas- 4·( { 〔3_(Trifluoromethyl)phenyl)carbonyl)amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanic acid (Compound No. 3 3 6 ) , ..r 〔 [(3,4-Dichlorophenyl)carbonyl]amino}phenyl 1 _(丨L 3 , )pyridine-2-yl]oxy}methyl)cyclobutylene residual acid (Compound No. 337), Fr / / 4- { 〔(2,3-dimethylphenyl)carbonyl]amino}phenyl)indole ratio D-but-2-yloxyoxindolemethyl)cyclobutanecarboxylic acid (Compound No. 338) I { ( ( 5_ { 4_ (cyclohexylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanine residual acid (compound No. 3 3 9 ) hi 〔 (5-{4-[(naphthalen-2-ylcarbonyl) Amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid (Compound No. 3 40 ) 1-( { 〔5-(4-{ 〔(3-Chloro-4-fluorobenzene) Carbonyl]amino]phenyl}pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 341) -231 - 200918053 1-( { 〔5-(4-{ 〔 (3, 4-Dimethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 342) 卜{[(5 - { 4 -[(phenyl) Carbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid (Compound No. 343) 1-( { 〔5-(4-{ 〔(4-ethylphenyl)carbonyl) Amino}phenyl)pyridin-2-yloxymethyl}cyclobutanecarboxylic acid (Compound No. 344) 1-[({5-[4-( { [4-methyl- 3-(3) Fluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 4 5 ) 1- ( { 〔5-(4-{ 〔 (2,4-dimethylphenyl)carbonyl]amino}benzene Pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 346) 1-( { 〔5-(4-{ 〔(2,5-Dimethylphenyl)carbonyl)amino Phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 347) 1-{ 〔(5-{4-[(Biben-3-yl)amino]benzene卩 卩 卩疋 卩疋 - 2-yl)oxy]methyl fluorenylcyclobutanecarboxylic acid (Compound No. 3 48 ) 1- ( { ( 5- ( 4- { 〔 (3,5-Dimethylphenyl)) Carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 349) 1-( { 〔5-(4-{ 〔 (2,6-monomethylbenzene) Alkylamino}phenyl)pyridin-2-yloxymethyl}cyclobutanecarboxylic acid (Compound No. 3 5 0 -232- 200918053 l-[ ( {5-[4-( { 〔 3-(methylsulfonyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 351) 1-( { 〔5-(4 -{[(3-air-4-methoxybenzyl) benzyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (compound No. 3 5 2 ) 1-( { 〔5-(4-{ 〔(3-methoxy-4-methylphenyl)anthracene Amino}phenyl)pyridin-2-yloxymethyl}cyclobutanecarboxylic acid (Compound No. 3 5 3 ) 1-( { 〔5-(4-{ 〔 (3 - chloro-4- Methane base) oryl] amine} phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (compound No. 3 5 4 ) 1-( { 〔5-(4-{ 〔 4-chloro-3-methylphenyl)carbonyl]amino}phenyl)pyridine-2-yloxyoxomethyl)cyclobutanecarboxylic acid (Compound No. 3 5 5 ) 1-{ 〔 (5-{ 4-[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid (Compound No. 356) 1- ( { 〔5-(4-{ 〔(3-Hydroxyphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 5 7 ) ({5-[4-({[3-(propyl-2-yl)))yl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound) No. 3 5 8 ) 1-[({5-[4-( { 〔3-(methylthio)phenyl)]]-amine-233- 200918053 phenyl]pyridin-2-yl}oxy )methyl]cyclobutanecarboxylic acid (Compound No. 3 5 9 ) 1-[ ( {5-[4-( { 〔4 -Chloro-3-(trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 6 0 ) 1- ( { [ 5-(4-{[(3-Cyanophenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 361) 1-[ ( {5 -[4-( { 〔3-(Trifluoromethoxy)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 3 6 2 ) 1 -( { 〔5-(4-{ 〔(4-Fluoro-3-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 363 1-( { 〔5-(4-{ 〔(3-chloro-4-methylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (compound) No. 364) 1-[({5-[4-( { [4-Chloro-3-(trifluoromethyl)phenyl]carbonyl)]amino)phenyl]pyridin-2-yl}oxy)methyl] Cyclopropanecarboxylic acid (Compound No. 3 6 5 ) 1-[({5-[4-( { 〔3-(Trifluoromethyl)phenyl)carbonyl)amino)phenyl]pyridin-2-yl}oxy )methyl]cyclopropanecarboxylic acid (Compound No. 3 66 ) 1-( { [5-(4-{ 〔(3,4-Dichlorophenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 3 67 ) -234- 200918053 1-({[5-(4-([3,4-Didecylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (compound number) 368 ) 1-( { 〔5-(4-{ 〔(3-Chloro-4-fluorophenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (compound) No. 3 69 ) 1-({[5-(4-{[(3,5-Dimethylphenyl)carbonyl]amino)phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 370) 1-{ 〔(5-{4-[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]A Cyclopropanecarboxylic acid (Compound No. 371) 1-[({5-[4-({[3-(propyl-2-yl)yl)]]yl}amino)phenyl]pyridin-2 -yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 3 72 ) 1-( { 〔5-(4-{ 〔(3 -Chloro-4-methoxyphenyl) yl)amino} benzene Pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 3 73 ) 1- [ ( { 5- [ 4- ( { [3-(Trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopentanecarboxylic acid (Compound No. 3 74 ) 3-( {5-[4 -( { 〔4 -Gas-3-(di-methyl)phenyl]mine}}amino)phenyl]pyridin-2-yl}oxy)-2,2-dimethylpropanoic acid (Compound No. 3 7 5 ) 3-{ 〔5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl)amino}phenyl-235- 200918053) pyridin-2-yl]oxan-2, 2-Dimethylpropionic acid (Compound No. 3 76 ) 3- { 〔5-(4-{ 〔(3,4-Dichlorophenyl)carbonyl)amino}phenyl)pyridin-2-yloxy } -2,2-Dimethylpropionic acid (Compound No. 3 77 ) 2.2- Monomethyl- 3-( {5-[4-( { 〔3-(二菊(methyl)phenyl))} Amino)phenyl]pyridin-2-yl}oxy)propionic acid (Compound No. 378) 2.2- _Methyl- 3-({5-[4-( { 〔3-(dimethoxymethoxy)phenyl) 】carbonyl}amino)phenyl]pyridin-2-yl}oxy)propionic acid (Compound No. 3 79 ) 1-[({5-[4-( { [3-(Trifluoromethoxy)phenyl)] Carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound No. 3 8 0 ) 1-( { 〔5-(4-{ [(4-Fluoro-3-methylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 8 1 ) 1-( { [5 -(4-{ 〔(3-chloro-4-methylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 382) 1-[ ( { 5 - [ 4 - ( { 〔4-oxo-3-(dimethyl)phenyl]indolyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 8 3 ) 1-[({5-[4-( { [3-(Trifluoromethyl)phenyl]carbonyl)amino)phenyl]pyrimidin-2-yl}oxy)methyl] Cyclobutanecarboxylic acid (Compound No. 3 84 ) -236- 200918053 1-( { 〔5-(4-{ 〔 (3,4 - _ _ _ _ _ yl) yl) yl)} phenyl) pyrimidine-2 _ Oxy]methyl)cyclobutanecarboxylic acid (compound No. 3 8 5 ) 1-( { 〔5-(4-{ 〔(3 - gas-4 - gas-based)) yl) Pyrimidine-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 3 8 6 ) 1-( { 〔5-(4-{ 〔(3,4-Dimethylphenyl)carbonyl)amine Benzyl)pyrimidin-2-yloxymethyl}cyclobutanecarboxylic acid (Compound No. 387) 1-[({5 -[3-Fluoro-4-({[3-(trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 8 8 ) 1-( { [ 5- ( 4- { 〔(3,5-Dimethylphenyl)carbonyl)amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 389) 1-{[(5-{4-[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyrimidin-2-yl)oxy]methyl }cyclobutanecarboxylic acid (compound No. 390) 1-[({5-[4-( { [3-(propyl-2-yl)phenyl)]indenyl}amino)phenyl]pyrimidin-2- Base oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 9 1) 卜({ 〔5-(4-{ 〔(3-Chloro-4-methoxyphenyl)carbonyl)amino} phenyl Pyrimidine-2-yloxymethyl}cyclobutanecarboxylic acid (Compound No. 3 92 ) 1-( { 〔5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl)amine }}-3-fluorophenyl)pyrimidine-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. -237- 200918053 3 93 ) l-[ ( {5-[4-( { 〔3- (trifluoromethoxy)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid Compound No. 3 94 ) 1-( { 〔5-(4-{ 〔(4-Fluoro-3-methylphenyl)carbonyl)amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropane Carboxylic acid (Compound No. 395) 1-( { 〔5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl)amino}phenyl)pyrimidin-2-yl]oxy}methyl) Cyclopropanecarboxylic acid (Compound No. 396) 1-[({5-[4-( { [4-Chloro-3-(trifluoromethyl)phenyl]carbonyl)]amino)phenyl]pyrimidin-2-yl }Oxo)methyl]cyclopropanecarboxylic acid (Compound No. 3 9 7 ) 1-[({5-[4-( { 〔3-(Trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyrimidine -2 _yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 3 9 8 ) 1-( { 〔5-(4-{ 〔(3,4-Dichlorophenyl)carbonyl)amino}phenyl Pyrimidine-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 3 99 ) 1-( { 〔5-(4-{ 〔(3- gas-4-carbyl) fluorenyl)amine Phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 400) 1-( { 〔5-(4-{ 〔(3,4-methylphenyl)) Amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid Item No. 401 ) 1-( { ( 5-(4-{ 〔(3,5-Dimethylphenyl)carbonyl)amino}benzene-238- 200918053 yl)pyrimidin-2-yloxycarbonylmethyl) Cyclopropanecarboxylic acid (compound number) 1- { 〔(5-丨4-[(5,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino}}pyrimidin-2-yl)oxy] Cyclopropanecarboxylic acid (compound number) 1-[({5-[4-({[3-(propyl-2-yl)phenyl))}}phenyl]pyrimidin-2-yl}oxy )methyl]cyclopropanecarboxylic acid (compound 404) 1-( { 〔5-(4-{ 〔(3 -chloro-4-methoxypropenyl)methyl)pyrimidin-2-yl)oxy }methyl)cyclopropanecarboxylic acid (compound 405) 1-[({5-[4-( { 〔3-(trifluoromethyl)phenyl)carbonyl})phenyl]pyrimidin-2-yl}oxy) Methyl]cyclopentanecarboxylic acid (compound 406) 3-( {5-[4-( { 〔4-gas-3-(dimethylmethyl)carbenyl)phenyl]pyrimidin-2- })Oxo)-2,2-dimethylpropionic acid (Hydration No. 407) 3-{ [5-(4-{ 〔(3,4- chlorobenyl; per yl)amino}pyrimidine-2 -yloxy}-2,2-dimethylpropionic acid (Compound No. 408) 2.2-Dimethyl-3-({5-[4-({[3 -(Trifluoromethyl)phenyl}amino)phenyl]pyrimidin-2-yl}oxy)propionic acid (compound number) 2.2-dimethyl-3-({5-[4-({[3 -(Trifluoromethoxy)phenylcarbonyl}amino)phenyl]pyrimidin-2-yl}oxy)propionic acid (Compound 402) Benzene 403 Amino-based number} Number of amine group number} Amine group) carbonyl 409 基] No. -239- 200918053 4 10) 3_{[5-(4-{ 〔(3-Chloro-4-methylphenyl)carbonyl)aminopurinylphenyl)pyrimidin-2-yl]oxy} 2,2-Dimethylpropionic acid (Compound No. 411) (Example 72) 1_[({5-[4-( { [4-Chloro-2-(trifluoromethyl)phenyl]aminocarbamidine) Manufacture of a residual acid (Compound No. 4 1 2 ) of aryl]phenyl]pyridin-2-yloxy)methyl]cyclobutanine (Compound No. 4 1 2 )

1-[({ 5-[4-({4-chloro-2-(trifluoromethyl)phenyl))aminomethyl)amino)phenyl]pyridin-2-yl}oxy) a mixture of tetrahydrofuran (4 m 1 ) and methanol (2 m 1 ) in a mixed solution of cyclobutanecarboxylic acid methyl ester (Compound No. 246) (0.161 g, 0.302 mmol) under ice cooling. The sodium aqueous solution (1 m 1 ) was stirred at room temperature for 1 hour, and the reaction mixture was neutralized with 1 Μ hydrochloric acid, diluted with ethyl acetate, and the organic layer was washed with saturated brine, Magnesium is dried, and the desiccant is filtered out. The liquid is concentrated under reduced pressure to obtain 1-[({5-[4(({-]-chloro-2-(trifluoromethyl)phenyl)aminocarbamyl) Alkyl) a crude crystal of the base of the group - 2 -yl}oxy)methyl]cyclobutanecarboxylic acid, obtained by mixing the obtained crude crystals with ethyl acetate and diisopropyl ether Recrystallization in the middle to give 1-(( { 5_[ 4 _ ( { 〔 4 - chloro-2 _ (dimethylmethyl) phenyl) phenyl hydrazinyl) yl) phenyl pyridin-2-yl } -240- 200918053 Oxygen)methyl]cyclobutanecarboxylic acid (0.13 g). (Example 73) The compound of the present invention, 1-(([5-(4-{ 〔)) (2-Chloro-4-fluorophenyl)aminomethylindenyl]amino}phenyl)pyrimidin-2-yl]amino}methyl)cyclobutanyl decanoic acid ester (Reference Synthesis Example 5) , 1-({[5-(4-{[(2,4-dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentane Benzyl carboxylate (synthesized according to the synthesis method of Example 49 using Reference Synthesis Example 1 - 10), substituted 1-[({5-[4-( { [4-chloro-2-(trifluoromethyl)) Phenyl]aminomethylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid methyl ester (Compound No. 246) gave the following compound of the present invention. -( { 〔5-(4-{ 〔(4-Fluoro-3-methylphenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate Acid (Compound No. 4 1 3 ) 1-( { (5-(4-([2-Bromo-5-methylphenyl)aminomethylindolyl)aminophenyl)pyridin-2-yl] Oxygen}methyl)cyclobutanecarboxylic acid Compound No. 414) 卜({ 〔5-(4-{ 〔(2-Chloro-4-fluoro-5-methylphenyl)aminomethylindolyl)amino}phenyl)pyridin-2-yl]oxy }Methyl)cyclobutanecarboxylic acid (Compound No. 4 1 5 ) Bu [({5-[4-( { 〔3-(Trifluoromethyl)phenyl]aminocarbamoyl-241 - 200918053 } Amine Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 4 1 6 ) 1-[ ( {5-[4-( { [4-Chloro-3-(trifluoro) Methyl)phenyl]aminomethylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 4 1 7 ) 1-( { 〔5-(4 -{[(2-Fluoro-5-methylphenyl)aminocarbamimidyl]-phenyl-phenyl}pyridin-2-yl]oxy}methyl)cyclobutanyl acid (Compound No. 4 1 8 ) 1 - (({5-[4-( { 〔2- gas-4-(trifluoromethoxy))]]]]]]]]]]]] )methyl]cyclobutanecarboxylic acid (Compound No. 4 1 9 ) 1-[({5-[4-( { 〔2-methyl(trifluoromethoxy)phenyl)aminomethylindenyl)amine Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound 420 ) 1-[({5-[4-( { 〔6-Fluoro-5-(trifluoromethyl)phenyl)aminomethylindenyl}amino)phenyl]pyridin-2-yloxy) Methyl]cyclobutanide Residual Acid (Compound No. 421) 1 - ( { 〔5-(4-{ 〔(3-Chlorophenyl)aminomethylindenyl)amino phenyl)pyridine-2-yl) Oxygen}methyl)cyclobutanecarboxylic acid (Compound No. 4 2 2 ) 1-({[5-(4-{[(3,5-Dichlorophenyl)aminomethylindenyl]))卩 疋 疋 疋 · · · · · ( 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物 化合物Aminomethylmercapto] -242- 200918053 Amino}phenyl)pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 4 2 4 ) 1-( { 〔5-(4-{ [(4-Cyano-2-methylphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 4 2 5 ) 1 -( { 〔5-(4-{ 〔(3-Chloro-2-fluorophenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 426) 1- ( { 〔 5- ( 4- { 〔 ( 4-tert-Butylphenyl) Amino A) Mercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 427) 1-[({5-[4-( { [2-methyl-5-) (Dimethoxymethyl)phenyl]aminomethylmethyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 4 2 8 ) 1-[ ( {5 -[4-( { 〔3-(propan-2-yl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (compound number 4 2 9 ) 1-( { 〔5-(4-{ 〔(4-Chloro-3-methoxyphenyl)aminomethylindenyl)amino phenyl)pyridin-2-yl]oxy}A Cyclobutanecarboxylic acid (Compound No. 4 3 0 ) 1-( { 〔5-(4-丨[(2,2-Difluoro-1,3-benzodioxan-5-yl)) Methylamino]amino}phenyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 431) 1- [ ( { 5- [ 4- ( { [ [ [ -(Trifluoromethyl)phenyl]amino]-243- 200918053 formazan}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 432) 1-[ ({5-[4-( { 〔6-chloro-5-(trifluoromethyl)phenyl)aminomethylindenyl)amine Phenyl]pyridine-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 4 3 3 ) 1-[ ( {5-[4-( { [4-Cyano-3-(trifluoro)) Methyl)phenyl]aminomethylmethyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 434) 1-( { 〔5-(4-{ [(2-Chloro-4-fluorophenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 43 5 ) 1-( { [5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindolyl]amino}-3-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate Acid (Compound No. 4 3 6 ) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amino}-2-fluorophenyl)pyridine-2 -yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 4 3 7 ) 1-( { 〔5-(2 -chloro-4-{ 〔(2-chloro-4- perphenyl) carbamic acid Amino}phenyl)pyridin-2-yloxymethyl}cyclobutanecarboxylic acid (Compound No. 43 8 ) 卜({ 〔5-(4-{ 〔(2-Chloro-4-fluorobenzene) Aminomethylamino]amino}-2-methylphenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Item No. 4 3 9 ) 1-( { 〔5-(4-{ 〔(5-Chloro-2-fluorophenyl)aminomethylindolyl)amino-244 - 200918053 }Phenyl)pyridine-2-yl Oxygen}methyl)cyclobutanine residual acid (Compound No. 440) 1-( { 〔5-(4-{ 〔(2 -chloro-5-fluorophenyl)aminomethylindenyl)amino}phenyl Pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 44 1 ) 1-( { 〔5-(4-{ 〔(2-Chloro-5-fluorophenyl)aminocarbamidine Amino] -3-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (compound No. 442) i_[ ( {5_[3_fluoro- 4-( { 〔2- Fluoro-5-(trifluoromethyl)phenyl]aminocarbamimidino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanic acid (Compound No. 443) 1-( { [5-(3-Fluoro-4-{[(2-fluoro-5-methylphenyl)aminomethylindolyl]amino phenyl)pyridin-2-yl]oxy}methyl)cyclobutane Carboxylic acid (Compound No. 4 4 4 ) 1-( { 〔5-(4-{ 〔(2-Chloro-5-fluorophenyl)aminomethylindenyl)amino}-2-fluorophenyl)pyridine- 2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 4 4 5 ) 1-[ ( {5-[2-Fluoro-4-() { 〔2-Fluoro! -5-(difluoromethyl)-based "Monthene-Based Methyl]amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutylenecarboxylic acid (compound number 446) {[-(2-Chloro-4-{[(2-chloro-5-fluorophenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}methyl) Butanecarboxylic acid (Compound No. 4 4 7 ) 1-[({5-[2-Chloro-4-({[[2-fluoro] 5-(trifluoro(methyl))yl]]------ Methylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 4 4 8 ) 1-( { 〔5-(4-{ 〔 (3-A Phenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid (Compound No. 449) 1-[ ( {5-[4-( { 〔 3-(Trifluoromethoxy)phenyl]aminocarbazinyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 450) 1-({[ 5-(4-{[(2,5-Dichlorophenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 45 1 1-[({5-[4-( { 〔4-fluoro-2-(trifluoromethyl)phenyl)amino) Mercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropane decanoic acid (Compound No. 4 5 2 ) 1-[ ( {5-[4-( { 〔4 - chloro- 2 -(Trifluoromethyl)benyl]aminophenylmethyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropane decanoic acid (Compound No. 4 5 3 ) 1-[ ( {5-[4-( { -6-chloro-4-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropene Residual acid (Compound No. 4 5 4 ) 1 -[ ( { 5 -[ 4 - ( { 〔 4 -Fluoro-3 -(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridine -2-yl}oxy)methyl]cyclopropene residue (Compound No. 455) 1-[({5-[4-( { [2-(Trifluoromethoxy)phenyl])aminocarbazide- 246- 200918053 ylamino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 456) 1- ( { 〔 5- ( 4- { 〔 ( 3-chloro-4- Fluorophenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 45 7 ) 1-[ ( {5-[4-( { 〔 2-chloro-4-(trifluoromethoxy)phenyl]aminol Amino]phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 4 5 8 ) 1-[ ( {5-[4-( { [2-methyl- 4- (Trifluoromethoxy)phenyl]aminomethylindenyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 4 5 9 ) 1-[ ( {5 -[4-( { 〔3-(Trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 460 1-{[(5-{4-[(cyclohexylaminomethyl)amino)phenyl}pyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid (Compound No. 461) 1-[ ({5-[4-( { fluoro] 5-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropane Carboxylic acid (Compound No. 4 6 2 ) 1-[({5-[4-( { [4-(Trifluoromethoxy)phenyl]aminocarbamoyl)amino)phenyl]pyridin-2- Base}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 4 6 3 ) 1-({[5-(4-{[(2,4-Dimethylphenyl)aminomethylindenyl)) Phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid Compound No. 247-200918053 464) 1-( { 〔5-(4-{ 〔(2-Chloro-4-carbyl)aminoglycolyl)amino}phenyl)pyridin-2-yl] Oxy}methyl)cyclopentanecarboxylic acid (Compound No. 465) 1-( { 〔5-(4-{ 〔(2-Fluoro-5-methylphenyl)aminomethylindenyl)amino}phenyl Pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid (Compound No. 466) 1- ( { [ 5- ( 4- { 〔 (2,4-Dimethylphenyl)aminocarbazinyl) Amino}phenyl)pyridin-2-yl]oxy}methyl)cyclohexanecarboxylic acid (Compound No. 467) 1-( { 〔5-(4-{ 〔 (2 - qi-4-Acetone) § Female genus base] ‧ female base phenyl) pyridin-2-yl] oxy} methyl) cyclohexane carboxylic acid (compound number 468) 1-( { 〔5-(4-{ 〔 (2 - gas-4-a-5-methylphenyl)aminomethyl aryl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 4 6 9 ) 1- ( { 〔5-(4-{ 〔(2- gas-4-carbyl))aminomethyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid ( Compound No. 470) 1-( { 〔5-(4-{ 〔(3 - qi-4-gashene) § female base Alkyl}amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 47 1) 1-( { 〔5-(4-{ 〔(3-Chlorophenyl) Aminomethylamino]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 472-248-200918053 1-( { 〔5-(4-{ 〔 (2 -Fluoro-5-methylphenyl)aminomethylindolyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 473) 1-( { 〔5- (4-{ 〔(3-Chloro-2-phenyl)aminomethyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 474) 1 -[({5-[4-( { [4-methyl-3-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl Cyclobutanecarboxylic acid (Compound No. 475) 1-(({5-[4-( { 〔4-fluoro-3-(trifluoromethyl)phenyl)aminomethylindenyl)amino)phenyl Pyrimidine-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 4 7 6 ) 1-( { 〔5-(4-{ 〔(4-Chloro-3-methoxyphenyl)amine Methyl hydrazino]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid ( Compound No. 477 ) 1-( { 〔5-(4-{ 〔(3-Chloro-4-methoxyphenyl)aminomethylindenyl)amino}phenyl)pyrimidin-2-yl]oxy}A Cyclobutanecarboxylic acid (Compound No. 4 7 8 ) 1- [ ( {5-[4-( { 〔3-(Proton-2-yl)phenyl]aminomethylindenyl)amino)phenyl Pyrimidine-2-yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 4 7 9 ) 1-[ ( {5-[4-( { [4-fluoro-2-(trifluoromethyl)benzene) Aminomethylamino}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (-249-200918053, Compound No. 4 8 0) 1- [( { 5- 〔 4 - ( { 〔2-Fluoro-5-(tridecyl)amino)phenyl]pyrimidin-2-yl}oxy compound No. 4 8 1 ) 1- 〔 ( { 5- 〔 4- ( { 〔 2- -5-(methylamino}amino)phenyl]pyrimidin-2-yl} (Compound No. 4 8 2 ) 1-(丨[5-(4-{ 〔(2_chloro-5-fluorophenyl)} Phenyl)pyrimidin-2-yl]oxy}methyl)cyclo 48 3 ) 1-( { 〔 5-( 4- { 〔(2-chloro-4-fluorophenyl}-3-fluorophenyl)pyrimidine-2 -yl]oxy}methyl material number 4 8 4 ) 1- ( { 〔 5-( 4- { 〔(2-chloro-5-fluorophenyl} -3-fluorophenyl)pyrimidin-2-yl]oxy} A No. 4 8 5 ) 1- 〔 ( { 5- 〔 3-Fluoro-4-( { 〔 2-fluoro-5-ylmethylmethyl}amino)phenyl]pyrimidin-2-yl acid (compound number 4 8 6 ) 1-( { 〔 5-( 3-fluoro-4-{ 〔(2-fluoro-5-)amino}phenyl)pyrimidin-2-yl]oxy}methyl No. 4 8 7 ) 1 - [(5-[4-(4-({[3-(Trifluoromethyl)amino)phenyl]pyrimidin-2-yl}oxy)fluoromethyl)phenyl]aminomethyl), methyl] Butanecarboxylic acid (trifluoromethyl)phenyl]aminooxy)methyl]cyclobutanecarboxylic acid)aminocarbamoyl]aminobutanecarboxylic acid (compound number) aminomethylmercapto group] Amino)cyclobutanecarboxylic acid (complex) aminomethylmercapto]amino)cyclobutanecarboxylic acid ((.trifluoromethyl)phenyl]amine}oxy)methyl]cyclobutane Carboxymethylphenyl)aminomercapto)cyclobutanecarboxylic acid (oxylated oxy)phenyl]aminocarboxamidinemethyl]cyclobutanecarboxylic acid (Chemical-250 200918053 Compound No. 4 8 8 ) 1-(({5-[4-( { 〔4-(Trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclo) Propane carboxylic acid No. 4 8 9 ) 卜({ 〔5-(4-{ 〔(4-chloro-3-methoxyphenyl)aminocarbamimidyl)amino}phenyl)pyrimidin-2-yl]oxypurine Cyclopropanecarboxylic acid (Compound No. 4 9 0 ) Bu (丨[5-(4-{ 〔(3-Chlorophenyl)aminomethylindolyl)amino}phenyl)pyrimidin-2-yl]oxy }Methyl)cyclopropanecarboxylic acid (Compound No. 491) 1-( { 〔5-(4-{ 〔(3-chloro-4-methoxyphenyl)aminomethylindenyl)amino}phenyl) Pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 4 9 2 ) 1-( { 〔5-(4-{ 〔(3-Chloro-4-fluorophenyl)aminocarbazinyl Amino}phenyl)pyrimidin-2-yloxymethyl}cyclopropanecarboxylic acid (Compound No. 493) 1-( { 〔5-(4-{ 〔 (2-fluoro-5-methylphenyl) Aminomethyl hydrazino]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid (Compound No. 494) 1- [ ( {5-(4-( { 〔4-Fluoro- 3-(Trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (Compound No. 495 ) 1- ( ( {5- [4-( { 〔4-fluoro-2-(trifluoromethyl)phenyl]aminocarbinyl)amino group Phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid (-251 - 200918053 Compound No. 496) 1 [( { 5 〔 4-( { [2-fluoro-5_(trifluoromethylhydrazine) Alkylamino)phenyl]pyrimidin-2-yl}oxy)methyl Compound No. 4 9 7 ) 1_[( { 5_[ 4_ ((3-(Trifluoromethoxy)))))phenyl) Pyrimidine_2_ylindoleoxy)methyl] #4 8 8) 1-[( { 〔2-methyl-4-(trifluoromethylmethylindenyl)amino)phenyl]pyrimidine_2 -yl}oxy) acid (compound No. 4 9 9 ) 1 -[ ( { 5-[ 4- ( { 〔 2-chloro-4-(trifluoromethoxymethyl)amino)phenyl]pyrimidine-2 -yl}oxy)methyl (Compound No. 5 0 0) 1-[( { 5-[ 4-( { 〔 2 ·(Trifluoromethoxy))}amino)phenyl]pyrimidin-2-yl}oxy Methyl] complex number 501 ) 1-( { 〔 5-(4-{ 〔(2-chloro-4-fluorophenyl)amine}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropane Carboxy 502) 1-( { 〔 5-(4-{ 〔(2-chloro-4-fluorophenyl)amine}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopentanecarboxyl 5 03 ) 1 -( { 〔5-(4-{ 〔(2-Fluoro-5-methylphenyl))}phenyl) -2 -yloxy}methyl)cyclopentanyl)phenyl]aminomethyl]cyclopropanecarboxylic acid (phenyl]aminocarboxamidine cyclopropanecarboxylic acid (oxy)phenyl]amine methyl] ring Propanecarboxy)phenyl]amino]cyclopropanecarboxylic acid phenyl]aminopyridinium cyclopropanecarboxylic acid (formylmethylmercapto) amino acid (compound number methylmercapto) amino acid (compound number amine Amidinoyl carboxylic acid (Compound-252-200918053, 5 04 ) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amine }Phenyl)pyrimidin-2-yl]amino}methyl)cyclobutanecarboxylic acid (Compound No. 5 0 5 ) 1-( { 〔5-(4-{ 〔 (2 -chloro-4 - gas-based) Aminomethyl]amino}-2,5-difluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (Compound No. 5 4 8 ) 1-( { 〔5- (4-{ 〔(2-oxo-4-aerocarbyl)aminoglycolyl]amino}-3,5-difluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylate Acid (Compound No. 5 4 9 ) (Example 74) 1-( { 〔5-(4-{ 〔(4-Chloro-3-(phenyl)phenyl)amino}phenyl)pyridine_2-yl Oxygen}methyl) Manufacturing butane carboxylic acid sodium salt (compound No. 506) a square of the [9]

1-( { 〔5-(4-{ 〔(4-Chloro-3-fluorophenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid (compound) No. 3 23 ) (50.0 mg, O.llOmmol) in a mixture of tetrahydrofuran (1.8 ml) and methanol (0·0 9 m 1 ), a 6 Μ aqueous sodium hydroxide solution (0.019 ml) was added and stirred at room temperature. After 20 hours, the obtained solid was filtered to give 1-({[4-(4-{[(4-chloro-3-fluorophenyl)-253-200918053 carbonyl]amino}phenyl)pyridine as a colorless powder. -2 -yloxy}methyl)cyclobutanecarboxylic acid sodium salt (25 mg). (Example 75) According to the production method of Example 7-14, 1 _[( { 5 _[ 4 _ ( { [ 3-(propan-2-yl)phenyl]carbonyl)amino)phenyl]pyrimidine- 2_yl}oxy)methyl]cyclobutanecarboxylic acid (Compound No. 3 91 ), which gives 1-[({ 5-[4-({[[3-(propyl))phenyl)carbonyl]amino)phenyl) Sodium pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylate (Compound No. 5 0 7 ). (Example 76) 1-[({5-[4-({][4-chloro-2-(trifluoromethyl)phenyl]aminomethylhydrazinyl)amino)phenyl]pyridin-2-yl Manufacture of sodium oxy)methyl]cyclobutanecarboxylate (Compound No. 508) [Chemical Formula 1 1 〇]

1-[({5-[4.( { [4-Chloro-2-(trifluoromethyl)phenyl]aminocarbamoylamino)phenyl]pyridin-2-yl}oxy) A a mixed solution of tetrahydrofuran (4 ml) and methanol (2 m 1 ) of cyclobutanecarboxylic acid (〇·13 g, 〇.24 mmol), and 6 NaOH aqueous solution (0.042 ml, 〇.25 mmol) was added dropwise under ice cooling. The reaction solution was warmed to room temperature and then concentrated under reduced pressure. The obtained solid was suspended in diisopropyl ether and filtered to give a colorless-254-200918053 solid solid ([Μ-[4-( { 〔 4-Chloro-2-(trifluoromethyl)anilinylcarbenyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclocarboxylic acid sodium salt (〇. 1 2 3 g). (Example 77) According to the production method of Example VII, compound numbers 4 1 3 , 415 , 416 , 417 , 418 , 449 , 419 , 420 , 421 , 451 , 423 , 424 , 425 ' 426 , 427 , 428 ' 429 , 430 , 431 , 433 , 434 ' 452 , 453 , 454 , 455 , 456 , 457 , 458 , 460 , 461 ' 464 , 468 , 502 of the compound of the invention, substituted ({5-[4- ( { [4-Chloro-2-(trifluoromethyl)phenyl]aminomethyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid (No. 4 1 2 The following compounds of the invention are obtained. 1-( { 〔5-(4-{ 〔(4-Fluoro-3-methylphenyl)aminocarbamoyl}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Sodium salt (No. 5 0 9 ) 1-( { 〔5-(4-{ 〔(2-Bromo-5-methylphenyl)aminocarbamoyl}phenyl)pyridine-2·yl]oxy }Methyl) Cyclobutanecarboxylic acid sodium salt (No. 5 1 0 ) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluoro-5-methylphenyl)aminomethyl) Sodium amidinophenyl)pyridin-2-yloxy]methyl)cyclobutanecarboxylate Compound No. 5 1 1 ) 1-[ ( {5-[4-( { 〔3-(Trifluoromethyl)) Phenyl]amino]methyl}amino)phenyl]pyridine-2 _yloxy)methyl]cyclobutanecarboxylic acid sodium]butane 414 422 432 459 1-[indenyl] aminide] amination Mercapto salt (sulfonium salt (-255-200918053 compound number 5 1 2) 1-[({5-[4-( { 〔4-chloro-3-(trifluoromethyl)phenyl))aminocarbazide Amidino)phenyl]pyridin-2-yloxy)methyl]cyclobutanine sodium salt (Compound No. 5 1 3 ) 1-( { 〔5-(4-{ 〔 (2-Fluoro- 5-methylphenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}A Sodium cyclobutanecarboxylate (Compound No. 5 1 4 ) 1-( { 〔5-(4-{ 〔(3-methylphenyl)aminocarbamoyl)amino}phenyl)pyridine-2 Sodium-oxy}methyl)cyclobutanecarboxylic acid sodium salt (Compound No. 515) 1-[({5-[4-( { [2-chloro-4-(trifluoromethoxy)phenyl])amine Sodium hydrazide}amino)phenyl]pyridine·2·yl}oxy)methyl]cyclobutanecarboxylic acid sodium salt (Compound No. 5 1 6 ) 1-[(丨5-[4-( { 〔2 -Methyl 4-(trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyridine-2-yloxy)methyl]cyclobutanecarboxylic acid sodium salt (Compound No. 5 1 7 ) 1-[({5-[4-( { 〔2-Fluoro-5-(trifluoromethyl)phenyl)aminomethylindenyl}amino)phenyl]pyridine-2-yl}oxy Sodium methylcyclobutanecarboxylate (Compound No. 5 1 8 ) 1-({[5-(4-{[(2,5-Dichlorophenyl)aminomethylindolyl]amino}benzene Sodium pyridinyl-2-yloxy}methyl)cyclobutanecarboxylate (Compound No. 5 1 9 ) 1-( { 〔5-(4-{ 〔(3 -Chlorophenyl)aminocarbamidine Sodium]amino}phenyl)pyridine-2 yl]oxy}methyl)cyclobutanecarboxylic acid sodium salt Compound No. -256- 200918053 520 ) 1-({[5-(4-{[(3,5-Dichlorophenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy }Methyl)cyclobutanecarboxylic acid sodium salt (Compound No. 5 2 1 ) 1-( { 〔5-(4-{ 〔(3-Chloro-4-methoxyphenyl)aminomethylindenyl)amine Sodium phenyl)pyridin-2-yloxy-2-methylcyclobutanecarboxylate (Compound No. 5 2 2 ) 1-(丨[5-(4-{ 〔(4-Cyano-2-) Methylphenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium salt (Compound No. 5 2 3 ) 1-( { 〔5-( 4-{[(3-oxo-2-pureyl)aminoglycolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium salt (Compound No. 524) 1-( { 〔 5-(4-{ 〔(4-tert-butylphenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Sodium salt (Compound No. 5 2 5 ) 1-[({5-[4-( { [2-Methyl-5-(trifluoromethyl)phenyl]aminocarbamoyl)amino)phenyl] Sodium pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate (compound number 5%) 1-[ ( { 5-[4-( { 〔3-(propan-2-yl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid sodium salt (Compound No. 5 2 7 ) 丨(5-(4-{ 〔(4-chloro-3-methoxyphenyl)aminocarbamimidyl)amino}phenyl)pyridin-2-yl]oxy }Methyl)cyclobutanecarboxylic acid sodium salt (Chemical-257-200918053 Compound No. 5 2 8 ) 1-( {[ 5-(4- {[ (2,2 - -·Μ-1,3 - benzene) And - sodium keto-5-yl)aminomercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium salt (Compound No. 529) 1-[ ( { 5-[4-( { 〔4-methyl-3-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutane Sodium carboxylate (Compound No. 5 3 0 ) 1-[({5-[4-( { [2-Chloro-5-(trifluoromethyl)phenyl]aminomethylindenyl)amino)phenyl Sodium pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate (Compound No. 5 3 1 ) 1-[ ( {5-[4-( { [4-amino-3-(dimethyl) Phenyl]aminomethylmercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate (Compound No. 5 3 2 ) 1-[({5-[4-( { [4-fluoro-2-(trifluoromethyl)phenyl]aminocarbamoyl)amino)phenyl]pyridine-2 -Sodium oxy)methyl]cyclopropanecarboxylic acid sodium salt (Compound No. 5 3 3 ) 1-[ ( {5-[4-( { 〔4-Chloro-2-(dimethyl)phenyl)amine Sodium methylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid sodium salt (Compound No. 5 3 4 ) 1-[ ( {5-[4-( { 〔2- Chloro-4-(trifluoromethyl)phenyl]aminomethyl]amino)phenyl]pyrostra-2-yl}oxy)methyl]cyclopropane sodium citrate (Compound No. 5 3 5 1-[(丨5-[4-({[4-fluoro-3-(trifluoromethyl)phenyl]aminocarbamoyl)amino)phenyl]pyridin-2-yl}oxy)) Sodium Cyclopropanecarboxylate-258- 200918053 Salt (Compound No. 53 6 ) 1-[(丨5-[4-( { 〔2-(Trifluoromethoxy)phenyl]aminomethylindenyl)amine Sodium phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid sodium salt (Compound No. 53 7 ) 1-( { 〔5-(4-{ 〔 (3 - qi-4- phenyl) Aminomethyl]Synyl}phenyl)pyridin-2-yl]oxy}methyl) ring Sodium alkanoic acid salt (Compound No. 5 3 8 ) 1-[({5-[4-( { 〔2-Chloro-4-(trifluoromethoxy)phenyl]aminomethylindenyl)amino) Sodium phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylate (Compound No. 53 9 ) 1-[ ( {5-[4-( { 〔2-methyl-4-(trifluoromethyl) Sodium oxy)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylate (Compound No. 5 4 0 ) 1- [ ( { 5- [ 4-({[3-(Trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid sodium salt (Compound No. 541 1 - {[(5-{4-[(cyclohexylaminomethyl)amino)phenyl}pyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid sodium salt (Compound No. 5 4 2 1-({[5-(4-{[(2,4-dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridine-2-yloxy}methyl)cyclopentane Sodium carboxylate (Compound No. 5 4 3 ) 1-( { 〔5-(4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl)amino}phenyl)pyridine-2 - Sodium oxy)methyl)cyclohexanecarboxylic acid sodium salt (Compound No. 54 4) -259- 200918053 1-( { 〔5- (4-{ 〔(2-Chloro-4-phenylphenyl)aminoglycolyl)amino}phenyl)pyrimidin-2-yl]oxy}A Sodium Cyclopropanecarboxylate (Compound No. 545) The structures, NMR data, and MS data of the compounds obtained in the examples are shown in Tables 1-1 to 1-49. -260- 200918053 [Table 1-1] Compound No. Structural Formula NMR MS RA, RA RB 1 2-Me〇-5-Me-Ph H 1H NMR (300 MHz, DMS0-D6) 6 ppm 1.24 (s, 6 H 2.24 (s. 3 H) 3.85 (s, 3 H) 4.34 (s. 2 H) 6.72 - 6.79 (m. 1 H) 6.90 (d, J=8.4 Hz, 1 H) 7.54 - 7.61 (m. 2 H) 7.63 - 7.70 (m. 2 H) 7.97 - 8.01 (m, 1 H) 8.22 (s, 1 H) 8.89 (s. 2 H) 9.47 Cs, 1 H) 12.38 - 12.48 (br, 1 H) MS (ESI/APCI Dual): 451 (M+1), 449 {M-1) 2 2-Me〇-5-Me-Ph CH3 1H NMR (300 MHz, DMSO-D6) t5 ppm 1.27 (s, 6 H ) 2.24 (s, 3 H) 3.63 (s, 3 H) 3.85 (s, 3 H) 4.37 (s, 2 H) 6.72 - 6.79 (m. t H) 6.90 (d, J=8.4 Hz, 1 H) 7.54 - 7.61 (m. 2 H) 7.63 - 7.70 (m. 2 H) 7.97 -8.01 Cm, 1 H) 8.22 (s, 1 H) 8.88 (s, 2 H) 9.47 (s, 1 H) MS (ESI /APCI Dual): 465 (M+1), 463 (M-1) 3 2-Et-Ph CH3 1H NMR (300 MHz, DMS0-D6) δ ppm 1.19 (t, J=7.5 Hz. 3 H) 1.27 (sr 6 H) 2.62 (q, J=7.5 Hz, 2 H) 3.63 (s, 3 H) 4.37 (s, 2 H) 7.00 - 7.05 (m. 1 H) 7.12 - 7.23 (m, 2 H) 7.56 - 7.62 (m. 2 H) 7.63 - 7.70 (m. 2 H) 7.77 - 7.82 (m, 1 H) 7.98 (s. 1 H) 8.89 (s, 2 H) M S (ESI/APCI Dual): 449 (M+1), 447 (M-1) 4 2,3-diMeO-Ph CH3 1H NMR (300 MHz, CDCI3) δ ppm 1.37 Cs, 6 H) 3.71 (s, 3 H) 3.88 (s. 6 H) 4.45 (s. 2 H) 6.64 - 6.69 (m, 1 H) 6.93 (s, 1 H) 7.03 -7.11 (m. 1 H) 7.32 (s. 1 H) 7.44 - 7.59 (m. 4 H) 7.71 - 7.77 (m, 1 H) 8.68 (s. 2 H) MS (ESI/APCI Dual): 481 CM+1), 479 (M-1) 5 2-CI-Ph CH3 1H NMR (300 MHz, CDCI3) δ ppm 1.37 Cs. 6 H) 3.71 Cs, 3 H) 4.45 (s, 2 H) 6.99 - 7.06 (m, 1 H) 7.11 - 7.21 (br. 2 H) 7.27 - 7.32 (m. 1 H) 7.34 - 7.39 (m, 1 H) 7.42 - 7.57 (m. 4 H) 8.16 - 8.22 (m, 1 H) 8.67 (s. 2 H) MS (ESI/APCI Dual): 455 (M+1), 453 (M-1) 6 2-Et-Ph H 1H NMR (300 MHz, DMSO-D6) c5 ppm 1.19 (t, J = 7.5 Hz. 3 H) 1.24 (s, 6 H) 2.62 (q, J=7.5 Hz, 2 H) 4.34 (s, 2 H) 6.98 - 7.06 (m, 1 H) 7.12 - 7.23 (m, 2 H) 7.54 - 7.62 (m, 2 H) 7.63 - 7.70 ( m, 2 H) 7.76 - 7.83 Cm. 1 H) 7.99 Cs, 1 H) 8.89 (s, 2 H) 9.20 (s. 1 H) MS (ESI/APCI Dual): 435 (M+1). 433 ( M-1) 7 2,3-diMeO-Ph H 1H NMR ¢300 MHz, DMS0-D6) δ ppm 1.23 (s. 6 H) 3.78 (s, 3 H) 3.81 (s, 3 H) 4.33 (s. 2 H) 6.66 - 6.72 (m, 1 H) 6.95 - 7.03 (m, 1 H) 7.54 - 7.70 (m, 4 H) 7.79 - 7.85 (m, 1 H) 8.44 (s, 1 H) 8.88 (s. 2 H) 9.53 (s, 1 H) MS (ESI/APCI Dual): 467 (M+1), 465 (M-1) 8 2-CI-Ph H 1H NMR (300 MHz, DMS0-D6) δ ppm 1.24 Cs, 6 H) 4.34 (s, 2 H) 7.01 - 7.09 (m, 1 H) 7.28 - 7.35 (m, 1 H) 7.45 - 7.49 (m, 1 H) 7.56 - 7.72 (m, 4 H) 8.15 - 8.21 ( m, 1 H) 8.37 (s, 1 H) 8.89 (s, 2 H) 9.57 - 9.61 Cm. 1 H) 12.38 - 12.46 (br, 1 H) MS (ESI/APCI Dual): 441 (M+1) , 439 (M-1J °γ°&gt;Β RA RB 9 3,4~diMe-Ph CH3 1H NMR ¢300 MHz, DMSO-D6) ¢5 ppm 1.27 (s. 6 H) 2.31 (s. 3 H) 2.32 Cs. 3 H) 3.63 (s, 3 H) 4.38 (s, 2 H) 7.30 (d, J=8.1 Hz. 1 H) 7.70 - 7.79 (m. 4 H) 7.89 - 7.95 (m, 2 H) 8.92 (s, 2 H) 10.25 (s, 1 H) MS (ESI/APCI Dual): 434 (M+1), 432 (M-1) 10 3,4-diMe-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.24 (s. 6 H) 2.31 (s, 3 H) 2.32 (s. 3 H) 4.35 (s, 2 H) 7.28 - 7.33 (m, 1 H) 7.69 - 7.80 (m. 4 H) 7.88 - 7.95 (m, 2 H) 8.92 Cs. 2 H) 10.26 (s, 1 H) MS (ESI/APCI Dual): 420 (M+1). 418 (M-1) -261 - 20091 8053 [Table 1-2] 〇H〇RA RB 11 2,3-diMeO-Ph Et 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.14 (t, J=7.1 Hz, 3 H) 1.21 (s, 3 H) 3.56 - 3.67 (m. 2 H) 3.78 (s, 3 H) 3.81 (s, 3 H) 4.08 (q. J=7.1 Hz, 2 H) 4.36 - 4.51 (m. 2 H) 4.99 - 5.04 ( m, 1 H) 6.67 -6.71 (m, 1 H) 6.99 (t. J=8.3 Hz, 1 H) 7.55 - 7.61 (m. 2 H) 7.64 -7.70 (m, 2 H) 7.80 - 7.85 (m. 1 H) 8.42 (s. 1 H) 8.89 (s, 2 H) 9.50 Cs. 1 H) MS (ESI/APCI Dual): 511 (M+1), 509 (M-1) 12 2,3-diMeO -Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm U7 (s, 3 H) 3.53-3.65 (m, 2 H) 3.78 (s, 3 H) 3.81 (s. 3 H) 4.35 - 4.45 (m , 2 H) 6.66 -6.72 (m, 1 H) 6.99 (t. J=8.4 Hz, 1 H) 7.56 - 7.62 (mr 2 H) 7.64 -7.70 (m, 2 H) 7.80 - 7.85 (m, 1 H 8.46 (s, 1 H) 8.88 (s, 2 H) 9.62 (s. 1 H) MS (ESI/APCI Dual): 483CM+1), 481 (M-1) 丫'RB α7 n RA RB 13 3,4_diMe-Ph CH3 1H NMR (300 MHz, CDCI3) δ ppm 1.38 (s, 6 H) 2.26 (s, 3 H) 2.29 (s, 3 H) 3.72 (s, 3 H) 4.47 (s, 2 H 7.14 (d, J=8.2 Hz, 1 H) 7.34 - 7.40 (m, 1 H) 7.45 - 7.48 (m, 1 H) 7.61 - 7.67 (m, 2 H) 7.70 - 7.81 (br, 1 H) 7.96 - 8.01 (m, 2 H) 8.76 (s. 2 H) MS (ESI/APCI Dual): 434 (M+1J, 432 (M-1) 14 3,4-diMe -Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.25 (s, 6 H) 2.20 (s. 3 H) 2.23 (s, 3 H) 4.37 (s, 2 H) 7.11 (d, J=8.4 Hz, 1 H) 7.49 - 7.54 (m, 1 H) 7.56 - 7.60 (m. 1 H) 7.88 - 7.94 (m, 2 H) 8.05 - 8.11 (m, 2 H) 9.03 (s, 2 H) 10.16 ( s, 1 H) 12.39 - 12.49 (br. 1 H) MS (ESI/APCI Dual): 420 (M+1), 418 (M-1) h °γ%Β 9 CH, RA RB 15 2-Me〇 -5-Me-Ph H 1H NMR (300 MHz. DMSO-D6) 5 ppm U 3 (s, 6H) 2.24 (s, 3H) 3.56 (d, J = 6.0 Hz. 2H) 3.85 (s, 3H) 6.68 ~ 6.80 (m. 1H) 6.85 - 6.93 (m, 1H) 7.00 (t J=6.0 Hz. 1H) 7.51 (dt J=9.0 Hz. 2H) 7.55 (dt J=9.0 Hz, 2H) 7.99 (s, 1H 8.19 (s, 1H) 8.58 (sr 2H) 9.39 (s, 1H) 12.27 (s, 1H) MS (ESI): 450 (M+1), 448 (M-1) 16 2-CI-Ph H 1H NMR C300 MHz. DMSO-D6) 5 ppm 1.12 Cs, 6H) 3.45 - 3.55 (m, 2H) 6.87 - 7.08 (m, 2H) 7.20 - 7.36 (m, 1H) 7.40 - 7.65 (m, 5H) 8.07 - 8.20 (m, 1H) 8.33 (s, 1H) 8.57 (s, 2H) 9.51 (s, 1H) 12.07 - 12.42 (br, 1H) MS (ESI): 440CM+1), 438 (M-1) 17 2,3-diMe〇-Ph H 1H NMR (300 MHz. DMSO-D6) (5 ppm 1.12 (s, 6H) 3.54 (dt J=6.5 Hz. 2H) 3.76 (s, 3H) 3.79 (s. 3H) 6.67 (d. J=8.4 Hz. 1H) 6.97 (t. J=8.4 Hz, 1H) 7.00 (t, J=6.5 Hz, 1H) 7.50 (d, J=9.0 Hz, 2H) 7.55 (d, J=9.0 Hz, 2H) 7.81 (d, J=8.4 Hz, 〗 H) 8.38 (s. 1H) 8.57 (s, 2H) 9.41 (s, 1H) 12.15-12.40 (br, 1H) MSCESI): 466 ( M+1), 464(M-1) s Η H RA RB 18 2-Me〇-5-Me - Ph Et MSCESI): 465(M+1) 19 2-Et-Ph Et MS (ESI): 449CM +1), 447CM-1) 20 2-CI-Ph Et MSCESI): 455(M+1), 453CM-1) 21 2-MeO-5-Me-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.63 (s, 6H) 2.23 (s. 3H) 3.84 (s. 3H) 6.70 - 6.80 (m. 1H) 6.86 - 6.95 (m, 1H) 7.46 - 7.78 (m, 4H) 7.98 (s. 1H) 8.21 (s.彳H) 8.85 (s, 2H) 9.44 (s. 1H) MS (ESI): 437 (M+1), 435 (M-1) -262- 200918053 [Table 1-3] 22 2- Et-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.16 (t J=7.5 Hz. 3H) 1.63 (s, 6H) 2.63 (q. J=7.5 Hz, 2H) 6.92 - 7.05 (m, 1H) ) 7.08 - 7.24 (m, 2H) 7.32 - 7.65 Cbr, 4H) 7.68 - 7.80 Cm, 1H) 8.61 - 8,85 (br, 2H) MS(ESI): 42KM+1), 419CM-1) 23 2-CI-Ph H 1H NMR (300 MHz_DMSO-D6) 5 叩m 1.62 (s. 6H) 6.95 - 7.06 (m, 1H) 7.20 - 7.35 (m, 1H) 7.40 - 7.70 (m, 5H) 8.01 - 8.18 (m, 1H) 8.78 (s.2H) 8.37 - 9.04 (br.1H) 9.50 -10.29 (br,1H)l2.42-12.93 Cbr, 1H) MS(ESI): 427CM+1), 425CM-1 24 2,3-diMeO-Ph Et MS (ESI): 48KM+1), 479CM-1) 25 2,3-diMeO-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.62 Cs, 6H) 3.75 (s, 3H) 3.79 (s, 3H) 6.60 - 6.70 (d, J=8.7 Hz, 1H) 6.96 (dd, J=8,1 Hz, 8.7 Hz. 1H) 7.42 - 7.65 (m. 4H) 7.78 (dd, J=8.1 Hz. 1H) 8.73 Cs, 2H) MS(ESI): 453(M+1), 45UM-1) 0 H'° ch' RA RB 26 2 - MeO—5 - Me - Ph CH3 MS (ESI): 479 (M +1), 467 EMI-1) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; =7.5 Hz. 2H) 2.24 (s, 3H) 3.85 (s, 3H) 4.37 (t. J=7.5 Hz, 2H) 6.75 (dd, J=2.1 Hz, 8.1 Hz, 1H) 6.90 (dd. J=2.1 Hz, 8.1 Hz. 1H) 7.57 (d, J=8.6 Hz, 2H) 7.65 (d, J=8.6 Hz, 2H) 7.99 (d, J=2.1 Hz. 1H) 8.21 (s, 1H) 8.88 Cs, 2H 9.46 Cs, 1H) 12.27 (s, 1H) MS (ESI): 465 (M+1), 463CM-1) r^RB RA RB 28 2-Me〇-5-Me_Ph GH3 MS (ESI): 476 (M+t). 474 (M-1) 32 2-Me〇-5-Me-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.39 - 1.58 (m. 2H) 1.80 -1.93 (m, 2H) 2.22 (s. 3H) 2.40 - 2.60 (m. 1H) 3.00 - 3.15 (m, 2H) 3.82 (s, 3H) 4.45 - 4.60 (m. 2H) 6.68 - 6.78 (m, 1H) 6.81 - 6.90 (m, 1H) 7.50 (d. J=9.0 Hz, 2H) 7.54 (d. J=9.0 Hz, 2H) 7.97 (s, 1H) 8.17 (s. 1H) 8.64 (s, 2H) 9.38 (s, 1H) 12.24 Cs, 1H) MS (ESI): 462 (M+1) s 460 (M-1) RA RB 29 2-MeO-5-Me-Ph Et MS (ESI): 490 (M +1). 488CM-1) 33 2-Me〇-5-Me-Ph H 1HNMR (300 MHz.DMS〇-D6) t5ppmU5-1.60(m,2H)1.65-1.85 (m. 3H) 2.10 - 2.35 ( m, 4H) 2.95 - 3.15 (m. 1H) 3.83 (s. 3H) 4.50 - 4.70 (m. 1H) 5.30 - 5.40 (m, 1H) 6.65 - 6.80 (m. 1H) 6.83 -6.95 (m. 1H) 7.52 (d, J=9.0 Hz, 2H) 7.56 (d, J=9.0 Hz, 2H) 7.97 (s, 1H) 8.17 (s, 1H) 8.67 (s, 2H) 9.38 (s, 1H) MS (ESI) : 462(M+1) f^l R,B r^Y^Y0 〇,rV^ 0 RA RB 30 2=MeO&quot;5^Me-Ph Et MSCESI): 490(M+〇, 488CM-1) 34 2 -MeO-5-Me-Ph H 1HNMR (300 MHz.DMS〇-D6)fippm1.30-1.55 (m,1H)1.55-1.80 (m, 2H) 1.90 - 2.10 (m, 1H) 2.23 Cs, 3 H) 2.30 - 2.60 Cm, 1H) 2.95 - 3.22 (m. 2H) 3.83 (s, 3H) 4.40 - 4.56 (m, 1H) 4.62 - 4.80 (m, 1H) 6.67 - 6.80 (m. 1H) 6.82 - 6.95 (m, 1H) 7.51 (d. J=9.0 Hz, 2H) 7.56 (d. J=9.0 Hz. 2H) 7.98 (s. 1H) 8.17 (s. 1H) 8.66 (st 2H) 9.38 (s, 1H) 12.35 (s, 1H) MS (ESI): 462 (M+1), 460 (M-1) -263 - 200918053 [Table 1-4] ryY, 〇Η H RA RB 31 2-Me〇-5-Me -Ph Et 1H NMR ¢300 MHz, CDCI3) δ ppm 1.18- 1.37 (m, 2H) 1.27 (t, J=7.2 Hz. 3H) 1.75 - 1.90 (m, 2H) 2.®0 -2.20 (m, 1H 2.20 - 2.30 (m. 2H) 2.31 (s, 3H) 2.86 - 3.03 (m. 2H) 3.83 (s, 3H) 4.16 Cq, J=7.2 Hz, 2H) 4.73 - 4.85 (m, 2H) 6.62 (s 1H) 6.72 - 6.8B (m, 2H) 7.08 (s. 1H) 7.40 - 7.52 (m. 4H) 7.93 (s. iH) 8.52 Cs, 2H) MSCESI): 504(M+1) 35 2-MeO 5-Me-Ph H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.03 - t.22 (m. 2H) 1.68 -1.80 (m. 2H) 1.88 - 2.05 (m, 1H) 2.12 - 2.30 (m, 5H) 2.82 - 3.00 (m. 2H) 3.84 (s, 3H) 4.60 - 4.75 (m, 2H) 6.75 (dd, J=2.1Hz, 8.4 Hz, 1H) 6.90 (d, J=8.4 Hz. IH) 7.51 (d Hz_ 2H) 7,54 (d. J=3.0 Hz. 2H) 7.99 (d, J=2.0 Hz, 1H) 8.19 (s , 1H) 8.65 (s, 2H) 9.40 (s. 1H) 12.11 (s, 1H) MS (ESI); 476 (M+1), 474 (M-1) RA RB 36 2-MeO - 5-Me— Ph Et MSCESI): 506 (M+1), 504 (M-1) 37 2-Me〇-5~Me-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 2.00 - 2.25 Cm. 2H) 2.24 (s. 3H) 3.40 - 3.80 (m, 4H) 3.84 (s, 3H) 4.09 (s. 2H) 4.24 - 4.35 (br. IH) 6.70 - 6.80 (mt IH) 6.85 - 6.95 (m. 1H) 7.47 - 7.64 (m, 4H) 7.99 Cs, IH) 8.19 (ε, IH) 8.67 Cs, 2H) 9.41 (s. IH) MSCESI): 478CM+1), 476(M-1) 丫, r, /r^T RA RB 38 2-MeO - 5-Me - Ph CH3 iH NMR (300 MHz. CDCI3) 0 ppm 1.39 (s. bH) 2.29 (s, 3H) 2.33 (s. 3H) 3.73 (s. 3H) 3.86 (s , 3H) 4.46 (s. 2H) 6.75 - 6.90 (m, 2H) 7.07 - 7.19 (m, 2H) 7.23 - 7.35 (m. 2H) 7.44 (s, IH) 7.96 (s, IH) 8.48 (s, 2H MS(ESI): 479CM+1), 477CM-1) 39 2-Me〇-5~Me-Ph H 1H NMR (300 MHz, CDCI3) δ ppm 1.40 (s, 6H) 2.21 (s, 3H) 2.28 (s. 3H) 3.79 (s. 3H) 4.45 (s. 2H) 6.70 - 6.85 (m. 2H) 7.00 - 7.07 (m, 1H) 7.15 - 7.23 (m, 1H) 7.33 - 7.50 (m, 3H) 7.93 (s, 1H) 8.41 (s, 2H) MSCESI): 465CM+1). 463CM-1) Η H RA RB 40 2,3-diMe〇-Ph Et MS (ESI): 480 (M+1), 478 (M-1) 41 2_Me〇-5-Me-Ph Et MS (ESI): 464 (M+1), 462CM-1) 42 2-Me〇-5-CF3-Ph Et 1H NMR ¢300 MHz, DMSO-D6) 5 ppm 1.07 tt, J=7.2 Hz. 3H) 1.63 Cs, 6H) 3.99 (s, 3H) 4.08 (q, J=7.2 Hz, 2H) 6.88 (d, J=8.4 Hz. IH) 7.22 (d, J=8.4 Hz. IH) 7.33 (dd, J=2.7 Hz. J=8.4 Hz. 1H) 7.54 ( d. J=8.9 Hz. 2H) 7.60 id. J=8.9 Hz. 2H) 7 99 (dd J=2 4 H7 J=8 4 Hz 1H) 8.33 (d. J=2.7 Hz. 1H) 8.54 (s. 1H) 8.57 (d. J=2.4 Hz. 1H) 9.52 Cs. 1H) MSCESI): 518CM+1), 516(M-1) 43 2-C Bu 4-F-Ph Et 1H NMR ¢300 MHz. DMSO -D6) 5ppm ).07 (t J=7.2 Hz, 3H) 1.63 (s. 6H) 4.08 (q, J=7.2 Hz. 2H) 6.80 - 6.92 (mt 1 H) 7.18 - 7.28 (m. 1H) 7.46 - 7.52 (m, 1H) 7.54 (d. J=8.7 Hz. 2H) 7.61 (d. J=8.7 Hz, 2H) 7.95 - 8.04 (m, 1H) 8.08 - 8.17 (m, 1H) 8.30 - 8.37 (m 2H) 9.43 (s, 1H) MS (ESI): 472CM+1), 470 (M-1) 44 3,5-diMe-PhCH2 Et 1H NMR (300 MHz. DMSO-D6) δ ppm 1.06 Ct. J =7.2 Hz. 3H) 1.62 (s. 6H) 2.26 (s. 6H) 4.07 (q. J=7.2 Hz. 2H) 4.24 (d, J=5.7 Hz. 2H) 6.58 (t. J=5.7 Hz, 1H ) 6.80 - 6.97 (m. 4H) 7.48 (d. J=8.9 Hz. 2H) 7.53 (d. J=8.9 Hz. 2H) 7.92 - 8.01 (m. 1H) 8.27 - 8.33 (m, IH) 8.62 (s, 1H) MSCESI): 462CM +1), 460(M-1) -264- 200918053 [Table 1-5] 45 cycioHexyl Et 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.00 - 1.43 (m. 5H) 1.06 (t J = 7.2 Hz, 3H) 1.48 - 1.91 (m. 5H) 1.62 (s. 6H) 3.36 - 3.58 (m. 1H) 4.07 (q, J=7.2 Hz, 2H) 6.09 (d, J=7.5 Hz, 1H) 6.86 (d, J=8.7 Hz. 1H) 7.44 (d, J=8.9 Hz, 2H) 7.52 (d, J=8.9 Hz. 2H) 7.95 (dd. J=2.7 Hz. 8.7 Hz. 1H) 8.29 Cd, J=2.7 Ηζ · 1H) 8.39 (s, 1H) MS (ESI): 426CM+1), 424 (M-1) 46 2,4-diMe-Ph Et 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.07 (t J=7.2 Hz, 3H) 1.63 (s, 6H) 2.22 (s. 3H) 2.24 (s. 3H) 4.08 (q. J=7.2 Hz. 2H) 6.88 (d. J=8.7 Hz. 1H) 6.93 - 7.03 (m, 2H) 7.53 (d. J=8.9 Hz. 2H) 7.58 (d. J=8.9 Hz. 2H) 7.63 - 7.69 (m. 1H) 7.87 (s. 1H) 7.98 (dd. J=2.4 Hz 8.7 Hz, 1H) 8.32 (d, J=2.4 Hz, 1H) 9.02 (s. 1H) MS(ESI): 448(M+1), 446(M-1) 47 3,5-diMe-Ph Et 1H NMR (300 MHz, DMSO-D6) dppm 1.07 (t. J = 7.2 Hz, 3H) 1.63 (s, 6H) 2.25 (s, 6H) 4 08 (q, J=7.2 H2, 2H) 6 .63 (s. 1H) 6.88 (d, J=8.9 Hz, 1H) 7.08 (s, 2H) 7.53 (d, J=8.9 Hz. 2H) 7.58 (d, J=8.9 Hz, 2H) 7.98 (dd, J=2.4 Hz. 8.9 Hz, 1H) 8.32 (d, J=2.4 Hz, 1H) 8.53 (s, 1H) 8.73 (s, 1H) MS (ESI): 448 (M+1), 446 (M-1) ) 48 2-CI-5-Me〇-Ph Et 1H NMR (300 MHz, DMS0-D6) 5 ppm 1.07 (t, J=7.2 Hz. 3H) 1.63 (s, 6H) 3.76 (s, 3H) 4.08 ( q, J=7.2 Hz. 2H) 6.64 (dd, J=3.0 Hz. 8.9 Hz, 1H) 6.88 (d, J=8.7 Hz, 1H) 7.36 (d. J=8.9 Hz. 1H) 7.55 (d. J = 9.0 Hz, 2H) 7.61 (d, J=9.0 Hz, 2H) 7.89 (d, J=3.0 Hz, 1H) 7.99 (dd, J=2.9 Hz, 8.7 Hz, 1H) 8.30 (s, 1H) 8.33 ( d. J = 2.9 Hz. 1H) 9.57 (s, 1H) MS (ESI): 484 (M+ 〇, 482 (M-1) 49 3-C 2 2-Me-Ph Et 1H NMR C300 MHz, DMSO-D6 5ppm 1.07 (t. J=7.2 Hz, 3H) Ϊ.63 (s, 6H) 2.32 (s, 3H) 4.08 (q, J=7.2 Hz, 2H) 6.85 - 6.91 (m, 1H) 7.14 - 7.24 ( m, 2H) 7.54 (d, J=9.0 Hz, 2H) 7.60 (d. J=9.0 Hz. 2H) 7.73 - 7.8t (m, 1H) 7.95 - 8.02 Cm, 1H) 8.18 (s, 1H) 8.31 &gt 8.34 Cm, 1H) 9.13 (s, 1H) MS (ESI): 468 (M+1), 466 (M-1) 50 1-Adamantyl Et 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.06 ( t. J=7.2 Hz, 3H) 1.62 (s, 6H) 1.51 - 1.74 (br, 6H) 1.88 - 2.12 (m, 9H) 4.08 (q. J=7.2 Hz. 2H) 5.90 (s. 1H) 6.85 (d, J=8.9 Hz, 1H) 7.41 (d. J=8.7 Hz, 2H) 7.50 (d, J=8.7 Hz, 2H) 7.95 (dd, J=2.4 Hz. 8.9 Hz, 1H) 8.29 (d. J=2.4 Hz, 1H) 8.34 (s, 1H) MS (ESI): 478 (M+〇. 476(M-1) 51 2,3-diMeO-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.61 (s. 6H) 3.77 (s. 3H) 3.81 ( s, 3H) 6.57 - 6.76 (m. 1H) 6.76 - 6.91 (m. 1H) 6.91 - 7.08 (m, 1H) 7.54 (d. J=8.7 Hz. 2H) 7.59 (d. J=8.7 Hz, 2H) 7.72 -7.89 (m, 1H) 7.89 - 8.04 (m· 1H) 8.33 (s, 1H) 8.40 (s, 1H) 9.43 (s, 1H) 12.48 (s, 1H) MS (ESI): 452 (M+1) ), 450 (M-〇52 2 - Me〇-5-Me_Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.63 (s. 6H) 2.25 (s. 3H) 3.86 (s, 3H) 6.76 (dd J =2.1 Hz. 8.4 Hz. 1H) $.87 (d. J=8.7 Hz. 1H) 6.91 (d, J=8.4 Hz, 1H) 7.54 {d, J=8.9 Hz. 2H) 7.59 (d. J= 8.9 Hz. 2H) 7.97 (dd, J=2.4 Hz, 8.7 Hz. tH) 8.00 (d, J=2.t Hz. 1H) 8.20 (s. 1H) 8.34 (d, J=2.4 Hz, 1H) 9.41 (s. 1H) 12.48 (s. 1H) MS(ESI): 436ίΜ+0. 434(M-1) 53 2-MeO_5-CF3-Ph H 1H NMR &lt;300 MHz, DMSO-D6) i ppm 1.61 (s. 6H) 3.98 (s, 3H) 6.83 - 6.88 (m, 1H) 7.17 - 7.25 (m. 1H) 7.30 - 7.36 (m. 1H) 7.51 -7.63 (m. 4H) 7.93 - 8.00 (m. 1H) 8.32 - 8.35 (m. 1H) 8.51 - 8.58 (m, 2H) 9.51 (s. 1H) 12.45 (s. 1H) MS(ESI): 490 (M+ 1), 488CM-1) 54 2-Ch4-F-Ph H tH NMR (300 MHz, DMSO-D6) 5ppm 1.61 (s. 6H) 6.83 - 6.89 (m, 1H) 7.17 - 7.28 (m, 1H) 7.45 - 7.65 (m. 5H) 7.93 - 8.00 (m, 1H) 8.08 - 8.t6 (m. 1H) 8.30 - 8.37 (m, 2H) 9.42 (s, 1H) 12.45 (s. 1H) MS (ESI): 444CM+1), 442(M-1) 55 3,5-diMe-PhCH2 H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.61 (s. 6H) 2.25 (s. 6H) 4.23 (d, J= 6.0 Hz. 2H) 6.57 (t J=6.0 Hz. 1H) 6.84 (d. J=8.6 Hz, 1H) 6.88 (s, 1H) 6.91 (s. 2H) 7.48 (d. J=9.2 Hz, 2H) 7.52 (d J=9.2 Hz, 2H) 7.93 (dd. J=2.7 Hz. 8.6 Hz. 1H) 8.30 (d. J=2.7 Hz. 1H) 8.61 (s, IH) 12.43 (s, 1H) MS (ESI) : 434(M+I), 432(M-1) 56 cycioHexyl H 1H NMR (300 MHz. DMSO-D6) &lt;5 ppm 1.08 - 1.42 Cm, 5H) 1.48 -1.90 (m. 5H) 1.62 (s. 6H) 3.40 - 3.58 (m, IH) 6.11 (d. J=7.8 Hz, IH) 6.85 (d, J= 8.7 Hz. IH) 7.45 (d, J=8.9 Hz. 2H) 7.52 (d J=8.9 Hz. 2H) 7.94 (dd. J=2.4 Hz. 8.7 Hz. IH) 8.31 (d. J=2.4 Hz, IH 8.39 (s, IH) 12.45 (s· IH) MSCESI): 398 (M+1). 396 (M-1) 57 2,4-diMe-Ph H IH NMR (300 MHz, DMSO-D6) dppm 1 -63 (s, 6H) 2.22 (s. 3H) 2.25 (s. 3H) 6.86 (d, J=8.7 Hz, 1H) 6.97 (d, J=8.t Hz. IH) 7.00 (s. 1H) 7.54 (d. J=9.0 Hz. 2H) 7.58 (d. J=9.0 Hz. 2H) 7.66 (d. J~8.1 Hz, 1H) 7 89 (s. 1H) 7.96 (dd, J=2.6 Hz. 8.7 Hz , 1H) 8.34 (d. J=2.6 Hz, 1H) 9.04 (s, IH) 12.38 - 12.67 (br, IH) MS (ESI): 420CM+1), 418(M-1) 58 3,5-diMe -Ph H IH NMR (300 MHz, DMSO-D6) δ ppm 1.63 (s, 6H) 2.25 (s, 6H) 6.63 (s. IH) 6.86 (d. J=8.6 Hz. 1H) 7.09 (s. 2H) 7.53 (d. J=8.7 Hz, 2H) 7.58 (d, J=8.7 Hz. 2H) 7.97 (dd, J=2.7 Hz, 8.6 Hz. IH) 8.34 (d. J=:2.7 Hz, IH) 8.55 ( s. IH) 8.74 (s. 1H) 12.47 (s. IH) MS (ESI): 420 (M+1), 418 (M-1) -265- 200918053 [Table 1-6] 59 2-Ch5-Me 〇-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.63 (s, 6H) 3.77 (s, 3H) 6.60 - 6.69 (m, 1H) 6.83 - 6.91 (m, 1H) 7.32 - 7.41 (m, 1H) 7.51 -7.67 (m, 4H) ) 7.87 - 7.93 (m, 1H) 7.93 - 8.02 (m, 1H) 8.27 - 8.40 Cm. 2H) 9.57 (s, IH) 12.47 (s, 1H) MSCESI): 456(M+1), 454(M- 1) 60 3-CI-2-Me-Ph H 1H NMR (300 MHz, DMSO-D6) dppm 1.63 Cs, 6H) 2.32 Cs, 3H) 6.81 - 6.90 (m, IH) 7.12 - 7.25 (m, 2H) 7.50 - 7.65 (m, 4H) 7.72 - 7.81 (m, 1H) 7.92 - 8.01 (m, 1H) 8.17 - 8.28 (br, 1H) 8.31 - 8.38 (m, IH) 9.09 - 9.27 Cbr, 1H) 12.35 - 12.57 (br. IH) MS (ESI): 440 (M+1), 438 (M-1) 61 1-Alamantyl H IH NMR (300 MHz, DMSO-D6) dppm 1.53 - 1.72 (m. 12H) 1.88 -2.09 (mt 9H) 5.89 (s, IH) 6.83 (d, J=8.6 Hz. 1H) 7.41 (d, J=8.4 Hz. 2H) 7.50 (d, J=8.4 Hz, 2H) 7.93 (dd, J=2.6 Hz, 8.6 Hz, IH) 8.30 Cd, J=2.6 Hz, 1H) 8.33 (s, 1H) 12.44 (s, 1H) MS (ES〇: 450(M+1), 448CM-1) 62 2-CI- Ph Et MS (ESI): 454 (M+1), 452 (M-1) 63 2-Et-Ph Et MS (ESI): 448 (M+1), 446 (M-1) 64 2-CI- Ph H 1H NMR ¢300 MHz, DMSO-D6) fi ppm 1.61 (s, 6H) 6.75 - 6.95 (m, 1H) 6.95 - 7.12 (m, IH) 7.2 1 - 7.39 (m, 1H) 7.39 -7.72 (mt 5H) 7.88 - 8.04 (m, IH) 8.10 - 8.25 (m, IH) 8.35 (s, 2H) 9.52 (s. 1H) 12.49 (s. IH) MS (ESI): 426(M+1), 424 (M-〇65 2-Et-Ph H IH NMR (300 MHz, DMSO-D6) dppm 1.20 Ct J=7.5 Hz. 3H) 1.63 (s, 6H) 2.64 (q, J=7.5 Hz. 2H) 6.82 - 6.90 (m, 1H) 6.97 - 7.07 (m, IH) 7.11 - 7.25 (m, 2H) 7.55 (d. J=9.0 Hz, 2H) 7.60 (d, J = 9.0 Hz, 2H) 7.76 - 7.85 (m, IH) 7.92 - 8.03 (m, 2H) 8.30 - 8.39 (m. IH) 9.12 Cs, 1H) 12.47 Cs. 1H) MS(ESI): 420 (M+1) ), 418(M-1) 0 丫ΓτΜτ Η H RA RB 66 2,3-diMeO-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.14 (s, 6H) 3.52 (d, J=6.0 Hz) 2H) 3.77 (s. 3H) 3.81 (s. 3H) 6.45 (t, J=6.0 Hz. 1H) 6.61 - 6.74 (m, 2H) 6 92 - 7.05 (rr&gt;, IH) 7.49 (ε, 4H) 7.59 - 7.60 (rr,. IH) 7.78 -7.89 (m, IH) 8.20 - 8.30 (m. IH) 8.37 (s. IH) 9.36 (s, 1H) 12.09 -12.30 (br. 1H) MS (ESI): 465(M+1) 67 2-MeO - 5-Me-Ph H 1H NMR ¢300 MHz, DMSO-D6) 5 ppm 1.15 (s, 6H) 2.23 (s, 3H) 3.47 - 3.59 (m. 2H) 3.84 Cs, 3H) 6.38 - 6.51 (m. IH) 6.67 (d, J=9.0 Hz, IH) 6.74 (dd, J=3.0 Hz, 9.0 Hz, 1H) 6.90 (d, J=9.0 Hz, 1H) 7.48 (s, 4H) 7.65 (dd, J= 3.0 Hz, 9.0 Hz, 1H) 8.00 (d. J=3.0 Hz, 1H) 8.17 (s, IH) 8.25 (d, J=3.0 Hz, tH) 9.33 (s, IH) 12.01 - 12.25 (br, IH) MSCESI): 449(M+1), 447(M-1) 70 2,4 -diMe-Ph H 1H NMR ¢300 MHz, DMSO-D6) 5 ppm 1.14 (s, 6H) 2.23 (s. 3H) 2.24 (s, 3H) 3.46 (s, 2H) 6.40 - 6.57 (br, 1H) 6.60 - 6.69 (m, IH) 6.90 - 7.03 (m, 2H) 7.40 - 7.58 (m, 4H) 7.60 - 7.70 (m, 2H) 8.17 - 8.29 (m, 2H) 9.35 (s, IH) MS (ESI): 433(M+1), 431 (M-1) 71 2-CI-Ph H IH NMR C300 MHz, DMSO-D6) dppm 1.14 (s, 6H) 3.52 (d, J=6.2 Hz. 2H) 6.45 (t J=6.2 Hz, IH) 6.61 - 6.76 (m, IH) 6.97 - 7.12 (m. IH) 7.25 - 7.38 (m, 1H) 7.39 - 7.60 (m, 5H) 7.60 - 7.74 (m, 1H) 8.11 - 8.30 (m, 2H) 8.31 (s, IH) 9.45 (s. 1H) 12.12 - 12.33 (br. 1H) MS (ESI): 439 (M+1), 437 (M-1) H 丫, Η H RA RB 68 2,4-diMe-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 0.90 ~ 0.96 (m, 2H) 1.02 -1.07 (m, 2H) 2.21 (s. 3H) 2.23 (s. 3H) 3.53 - 3.60 (m, 2H) 6.55 -6.65 (m, 2H) 6.93 - 7.00 (m, 2H) 7.48 (s, 4H) 7.65 - 7 .70 (m, 2H) 7.84 (s, 1H) 8.23 (s, 1H) 8.96 (s. 1H) 12.30 - 12.39 (br, 1H) MS (ESI): 431CM+1) 72 2-GI-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 0.90 - 0.96 (m, 2H) 1.01 -1.09 (m, 2H) 3.53 - 3.63 (m. 2H) 6.56 - 6.65 (m, 2H) 7.04 (t, J=7.9 Hz, 1H) 7.31 (t J=7.9 Hz, 1H) 7.46 (d, J=7.9 Hz, 1H) 7.50 (s, 4H) 7.66 (dd. J=2.4 Hz, 8.7 Hz. 1H) 8.18 (d. J =7.9 Hz, IH) 8.24 (d. J=2.4 Hz, 1H) 8.31 (s, 1H) 9.44 (s, 1H) 12.10 - 12.50 (br, 1H) MS(ESI): 437CM+1) -266- 200918053 [Table 7] RA RB 69 2,4-diMe-Ph H 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.49 - 1.60 (m, 2H) 1.87 -2.00 (m_ 2H) 2.21 (s,3H) 2.23 (s,3H) 5 3.15-3.43(m.2H) 3.57 (d, J=6.2 Hz, 2H) 3.71 - 3.8t (m, 2H) 6.54 (t, J=6.2 Hz. tH) 6.60 -6.67 (m , 1H) 6.93 - 7.01 (m, 2H) 7.48 (s, 4H) 7.61 - 7.70 (m, 2H) 7.86 (s, 1H) 8.22 - 8.28 (m, 1H) 8.99 (s, 1H) 12.20 - 12.75 (br , 1H) MS(E$I): 475CM+1) 73 2-Cl-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.49 - 1.61 (m, 2H) 1.86 ~ 2.00 (m. 2H) 3.18 - 3.48 (m, 2H) 3.58 (d, J=6.4 Hz, 2H) 3.72 -3.81 (m, 2H) 6.55 Ct, J=6.4 Hz, 1H) 6.60 - 6.68 (m, 1H) 7.00 -7.06 (m, 1H) 7.26 - 7.36 (mt 1H) 7.43 - 7.49 (m, 1H) 7.51 (s, 4H) 7.62 - 7.68 (m, (H) 1 . RB 74 2-Me〇-5-Me~Ph ch3 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.25 (s, 6 H) 2.24 (s, 3 H) 3.62 (s, 3 H) 3.85 (s, 3 H) 4.31 (s, 2 H) 6.72 - 6.78 (m. 1 H) 6.83 -6.93 (m, 2 H) 7.51 - 7.62 (mt 4 H) 7.94 - 8.01 (m, 2 H) 8.20 (s, 1 H) 8.41 - 8.44 (m, 1 H) 9.42 (s, 1 H) MS (ESI/APCI Dual): 464 (M+1), 462 (M-1) 75 2,3-diMeO-Ph ch3 1H NMR (300 MHz, CDCI3) 5ppm 1.33 Cs. 6 H) 3.71 (s, 3 H) 3.86 (s, 3 H) 3.87 (s. 3 H) 4.37 (s, 2 H) 6.65 (dd, J=8.3. 1.2 Hz, 1 H) 6.80 (m, 1 H) 7.00 (s, 1 H) 7.06 (t. J=8.3 Hz. 1 H) 7.44 (s, 1 H) 7.48 (s. 4 H) 7.72 - 7.80 Cm. 2 H) 8.32 - 8.34 (m, 1 H) MS (ESI/APCI Dual): 480 (M+1), 478 (M-1) 76 2-CI-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.33 (s, 6 H) 3.71 (s, 3 H) 4.37 (s, 2 H) 6.78 - 6.83 (m, 2 H) 6.98 - 7.05 (m. 1 H) 7.12 ( s, 1 H) 7.24 - 7.32 (m, 1 H) 7.33 - 7.38 (m. 1 H) 7.44 - 7.53 (m, 4 H) 7.74 - 7.79 (m. 1 H) 8.18 - 8.22 (m. 1 H) 8.32 - 8.34 (m. 1 H) MS (ESI/APCI Dua〇:454 (M+1), 452 (M-1) 77 3-Et-Ph ch3 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.18 ( t J=7-5 Hz, 3 H) 1.25 (s, 6 H) 2.58 (q, J=7.5 Hz. 2 H) 3.62 (s, 3 H) 4.31 (s, 2 H) 6.81 - 6.89 (m. 2 H) 7.15 - 7.22 (m, 1 H) 7.23 - 7.29 (m. 1 H) 7.31 - 7.35 (m, 1 H) 7.51 - 7.62 (m. 4 H) 7.97 (dd. J=8.7, 2.6 Hz, 1 H) 8.42 (d. J=2.6 Hz, 1 H) 8.65 (s, 1 H) 8.77 (s, 1 H) MS (ESI/APCI Dual): 448(M+1) 78 3,5-diMe- Ph ch3 1H NMR ¢300 MHz, DMSO-D6) 5 ppm 1.25 (s, 6 H) 2.24 (s, 6 H) 3.62 (s, 3 H) 4.31 (s, 2 H) 6.60 - 6.64 (m. 1 H 6.83 - 6.89 (m, 1 H) 7.08 (s. 2 H) 7.51 - 7.61 (m, 4 H) 7.97 (dd. J=8.7, 2.6 Hz. 1 H) 8.41 - 8.44 (m. 1 H) 8.54 (s, 1 H) 8.75 (s. 1 H) MS (ESI/APCI Dual): 448 (M+1) 79 2,4-diMe-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.32 (s, 6 H) 2.26 (s, 3 H) 2.33 (s, 3 H) 3.70 (s, 3 H) 4.36 (s. 2 H) 6.29 (s. 1 H) 6.66 (s, 1 H) 6.73 -6.83 (m , 1 H) 7.00 - 7.11 (mt 2 H) 7.28 - 7.35 (m, 1 H) 7.40 (s, 4 H) 7.65 - 7.76 (m, 1 H) 8.24 - 8.33 (m, ί H) MS (ESI/APCI Dual): 448 (M +1) 80 2-Et-Ph ch3 1H NMR (300 MHz, CDCI3) 5ppm 1.23 (t, J=7.54 Hz, 3 H) 1.33 (s. 6 H) 2.68 (q, J=7.51 Hz, 2 H) 3.70 (s, 3 H) 4.36 (s, 2 H) 6.14 -6.16(m.1H)6.41-6.44(m,1H)6.77-6.81(m,1H)7.23-7.35 (m. 4 H) 7.41 - 7.48 (m, 4 H) 7.72 - 7.76 (m, 1 H) 8.30 -8.32 (m, 1 H) MS (ESI/APCI Dual): 448 (M+1) 81 cycloHexyl ch3 1H NMR (300 MHz, CDCI3) 0 'ppm 1.05 - 1.25 (m, 2 H) 1.24 -1.50 (m, 8 H) 1.49 - 1.62 (m. 2 H) 1.66 - 1.80 (m, 2 H) 1.91 -2.08 (m, 2 H) 3.51 - 3.77 (m, 4 H) 4.37 (s. 2 H) 4.53 (d, J=6.99 Hz, 1 H) 6.17 (s, 1 H) 6.75 - 6.85 (m. 1 H) 7.32 - 7.53 Cm. 4 H) 7.71 - 7.79 (m, 1 H) 8.30 - 8.35 (m, 1 H) MS (ESI/APCI Dual): 426 (M+1) 82 2_Me〇-5-Me_Ph H 1H NMR ¢300 MHz. DMSO-D6) 5 Ppm 1.23 (s, 6 H) 2.24 (s, 3 H) 3.85 (s, 3 H) 4.28 (s. 2 H) 6.72 - 6.79 (m, 1 H) 6.83 - 6.93 (m, 2 H) 7.50 - 7.62 (m, 4 H) 7.93 - 8.02 (m. 2 H) 8.20 (s, 1 H) 8.39 -8.45 Cm. 1 H) 9.42 Cs, 1 H) 12.28 - 12.43 Cbr. 1 H) MS (ESI/APCI Dual): 450 (M+1), 448 (M-1) -267- 200918053 [Table 1 - 8] 83 2,3-diMeO-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.23 (s, 6 H) 3.78 (s. 3 H) 3.81 (s, 3 H) 4.28 (st 2 H) 6.69 (dd, J=8.3, 1.3 Hz. 1 H) 6.84- 6.89 (m, 1 H) 6.99 (t, J=8.3 Hz. 1 H) 7.51 - 7.63 (m, 4 H) 7.80 - 7.85 (m. 1 H) 7.95- 8.00 (m, 1 H) 8.37 - 8.45 (m, 2 H) 9.44 (s, 1 H) 12.31 - 12.39 Cbr, 1 H) MS (ESI/APC1 Dual): 466 (M+l). 464 (M-1) 84 2-CI-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.23 (s, 6 H) 4.28 (s, 2 H) 6.87 (d. J = 8.7 Hz, 1 H) 7.00 - 7.08 (m, 1 H) 7.27 - 7.35 ( m, 1 H) 7.45 - 7.49 (m. 1 H) 7.53 - 7.64 (m. 4 H) 7.95 - 8.00 (m, 1 H) 8.16 - 8.21 (m, 1 H) 8.35 (s, 1 H) 8.41 - 8.45 (m, 1 H) 9.53 (s, 1 H) 12.32- 12.38 (br, 1 H) MS (ESI/APCI Dual): 440 (M+1). 438 (M-1) 85 3-Et-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm U8 Ct, J=7.5 Hz. 3 H) 1.23 (s, 6 H) 2.58 (q, J=7.5 Hz, 2 H) 4.28 (s, 2 H) 6.79 - 6.90 (m, 2 H) 7.19 (m, 1 H) 7.23 - 7.29 (m, 1 H) 7.30 - 7.36 (m, 1 H) 7.50 -7.62 (m, 4 H) 7.97 (dd, J=8.6 t 2.6 Hz, 1 H) 8.43 (m, 1 H) 8.65 (s, 1 H) 8.77 (s, 1 H) 12.31 - 12.39 (br, 1 H) MS (ESI/APCI Dual): 434 (M+t) 86 3t5-diMe-Ph H 1H NMR (300 MHz, DMSO-D6) &lt;5 ppm 1.23 (s, 6 H) 2.24 (s, 6 H) 4.28 (s, 2 H) 6.62 (s, 1 H) 6.83 - 6.89 (m. 1 H) 7.08 (s, 2 H) 7.51 - 7.61 (m. 4 H) 7.97 (dd, J=8.6. 2.6 Hz, 1 H) 8.41 - 8.44 (m, 1 H) 8.55 (s, 1 H) 8.76 (s, 1 H) 12.31 - 12.38 (br, 1 H) MS (ESI/APCI Dual): 434 (M+1) 87 2,4-diMe-Ph H 1H NMR (300 MHz, DMSO-D6) dppm 1.22 (s, 6 H) 2.21 Cs, 3 H) 2.23 (s, 3 H) 4.28 (s, 2 H) 6.86 (d. J=8.7 Hz. 1 H) 6.91 - 7.02 (rn. 2 H) 7.56 (d. J=2.2 Hz, 4 H) 7.66 (d , J=8.4 Hz, 1 H) 7.92 - 8.00 (m, 2 H) 8.41- 8.44 Cm, 1 H) 9.11 (s, 1 H) 12.28 - 12.41 (br, 1 H) MS CESI/APCI Dual): 434 (M+1), 432 (M-1) 88 2-Et-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.14 - 1.26 (m, 9 H) 2.62 (q, J=7.62 Hz, 2 H) 4.29 (s, 2 H) 6.84 - 6.89 (m, 1 H) 6.98 - 7.05 (m, 1 H) 7.12 - 7.22 (m, 2 H) 7.53 - 7.61 (m, 4 H) 7.78 - 7.82 (m , 1 H) 7.93 - 8.00 (m, 2 H) 8.41 - 8.44 (m, 1 H) 9.12 - 9.16 (m, 1 H) 12.31 - 12.37 (br. 1 H) MS (ESI/APCI Dual): 434 ( _) 89 cycloHexyl H 1H NMR (300 MHz, DMSO-D6) d ppm 1.07 - 1.40 (m. 5 H) 1.22 (s, 6 H) 1.48 - 1.60 (m, 1 H) 1.60 - 1.73 (m, 2 H) 1.74 - 1.87 (m, 2 H) 3.40 - 3.54 (m, 1 H) 4.27 (s, 2 H) 6.11 (d, J=7.93 Hz, 1 H) 6.81 - 6.88 (m, 1 H) 7.41 - 7.55 (m. 4 H) 7.94 Cdd. J=8.70. 2.64 Hz. 1 H) 8.35 - 8.45 (m, 2 H) MS (ESI/APCI Dual): 412 (M+ 1) 90 2,4-diMe-Ph Na 1H NMR (300 MHz. DMSO-D6) i5 ppm 1.15 (s, 6 HJ 2.23 Cs, 3 H) 2.25 (s, 3 H) 4.33 (s, 2 H) 6.65 (d, J=8.7 Hz, 1 H) 6.88 - 6.97 (m, 2 H) 7.13 - 7.20 (m, 2 H) 7.40 - 7.46 (m, 2 H) 7.46 - 7.52 (m. 1 H) 7.69 (dd , J=8.6, 2.6 Hz. 1 H) 8.32 (d, J=2.6 Hz, 1 H) 9.94 (s, 1 H) 11.08 (s. 1 H) MS (ESI/APCI Dual): 434 (M-Na +2) .丫%日rr0^7 RA RB 91 2,4-diMe-Ph H 1H NMR ¢300 MHz, DMSO-D6) 5ppm 0.95 - 1.18 (m, 2H) Ϊ.13 -1.25 (m, 2H) 2.23 (s, 3H) 2.24 (s, 3H) 4.40 (s, 2H) 6.85 - 6.92 (m, 1H) 6.92 - 7.03 (m, 2H) 7.52 - 7.60 (m. 4H) 7.63 - 7.70 (m. 1H) 7.92 - 8.07 ( m, 2H) 8.40 - 8.42 (m. 1H) 9.11 - 9.30 (br, 1H) 12.30 -12.49 (br, IH) MS (ESI): 432CM+1J, 430(M-1) 93 2-CH4-F- Ph H 1H NMR (300 MHz. DMSO-D6) ppm 0.98 - 1.07 (m, 2H) 1.15 -1.24 (m. 2H) 4.38 (s. 2H) 6.88 (d, J=8.4 Hz, 1H) 7.21 (dt, J=3.2 Hz, 9.0 Hz, 1H) 7.48 (dd, J=3.2 Hz, 8.6 Hz. 1H) 7.54 (d, J=8.9 Hz, 2H) 7.60 (d, J=8.9 Hz, 2H) 7.96 (dd, J=2.4 Hz, 8.4 Hz, 1H) 8.11 (dd, J=6.0 Hz, 9.0 Hz, 1H) 8.33 (s. IH) 8.41 (d, J=2.4 Hz, IH) 9.44 (s, 1H) 12.25 - 12.52 (br, 1H) MS (ESI): 456 (M+1), 454CM-1) 94 3,5-diMe-Ph H IH NMR (300 MHz, DMSO-D6) 5 ppm Γ00 - 1.10 (m. 2H) 1.15 1.25 (m, 2H) 2.24 (s, 6H) 4.38 (s, 2H) 6.62 (s, IH) 6.89 (d, J=8.7 Hz. 1H) 7.08 (s. 2H) 7.53 (d, J=9.0 Hz , 2H) 7.58 (d, J=9.0 Hz, 2H) 7.97 (dd, J=2.4 Hz. 8.7 Hz. IH) 8.41 (d, J=2.4 Hz, 1H) 8.54 (s, 1H) 8.74 (s, IH) 12.38 (s, IH) MS (ESI): 432CM+1), 430CM-1) 95 2-Me〇-5-CF3-Ph H 1HNMR( 300 MHz, DMS〇-D6)5ppm1.00-U)8(m,2H)U6-1.24 (m, 2H) 3.98 (s, 3H) 4.38 (s, 2H) 6.89 (d, J=8.9 Hz, 1H 7.21 (d, J=8.7 Hz, 1K) 7.33 (dd, J=2.4 Hz, 8.7 Hz, 1H) 7.55 (d, J=8.7 Hz, 2H) 7.60 (d, J=8.7 Hz, 2H) 7.97 ( Dd, J=2.6 Hz, 8.9 Hz. 1H) 8.42 (d, J=2.4 Hz, 1H) 8.54 (s, IH) 8.56 (d, J=2.6 Hz, 1H) 9.54 (s, 1H) 12.16 - 12.60 ( Br, 1H) MS(ESl): 502 (M+U 500CM-1) -268- 200918053 [Table 1-9] 96 2,3-diMeO-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.00 - 1.10 (m, 2H) 1.15 -1.25 (m. 2H) 3.77 (s, 3H) 3.81 (s, 3H) 4.39 (s, 2H) 6.69 (d, J=8.4 Hz, 1H) 6.89 (d. J= 8.7 Hz. 1H) 6.99 (dd, J=8.1 Hz, 8.7 Hz, 1H) 7.55 (d, J=9.0 Hz. 2H) 7.60 (d, J=9.0 Hz, 2H) 7.83 (d, J=8.1 Hz, 1H) 7.97 (dd, J 2.4 Hz, 8.7 Hz. 1H) 8.35 — 8.45 (m. 2H) 9.44 (s. 1H) 12.35 - 12.45 (br. 1H) MS (ESI): 464 (M+1), 462(M-1) 97 2-CI-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.10 - 1.06 Cm, 2H) 1.15 -1.23 (m. 2H) 4.38 (s, 2H) 6.89 (d, J=8.7 Hz, 1H) 7.03 (t, J=7.1 Hz, 1H) 7.30 (tT J=7.3 Hz, 1H) 7.46 (d, J=8.1 Hz, 1H) 7.55 (d. J=9.0 Hz, 2H) 7.60 (d , J=9.0 Hz, 2H) 7.96 (dd, J=9.0 Hz, 2.7 Hz, 1H) 8.17 (d, J=8.4 Hz. 1H) 8.33 (s, 1H) 8.41 (d. J=2.7 Hz, 1H) 9.51 (s, 1H) 12.26 - 12.40 (br, 1H) MS (ESI): 438 CM +1) 98 2-Et-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.00 - 1.06 (m, 2H) 1.15 -1.21 (m, 5H) 2.62 (q, J=7.8 Hz, 2H) 4.38 (s, 2H) 6.88 (d, J=8.7 Hz, 1H) 7.01 (t, J=6.9 Hz, 1H) 7.10 - 7.21 ( m, 2H) 7.54 (d. J=9.0 Hz, 2H) 7.59 (d, J=9.0 Hz, 2H) 7.79 (d, J=6.9 Hz, 1H) 7.90 - 7.99 (m, 2H) 8.40 (d, J =2.4 Hz, 1H) 9.12 (s. 1H) 12.30 - 12.50 (br. 1H) MS (ESI): 430CM+1) RA RB 92 2,4-diMe-Ph H 1H NMR ¢300 MHz. DMSO-D6) 5 ppm 1.81 - 2.10 Cm, 4H) 2.21 (s, 3H) 2.23 (s, 3H) 2.32 - 2.49 (m, 2H) 4.53 (s, 2H) 6.86 (d, J=8.7 Hz, 1H) 6.94 - 6.99 ( m, 2H) 7.54 (d, J=8.9 Hz, 2H) 7.59 (d, J=8.9 Hz. 2H) 7.63 - 7.70 (m, 1H) 7.89 (s, 1H) 7.97 (dd. J=2.4 Hz, 8.7 Hz, 1H) 8.44 Cd, J=2.4 Hz, 1H) 9.06 Cs, 1H) 12.35 - 12.41 (br, 1H) MS(ESI): 446(M+1 ), 444 (M-1), 丫. X· Η H RA RB 99 PhCH2 ch3 1H NMR (300 MHz, DMSO-D6) 5 ppm i.26 (s, 6 H) 3.63 (s. 3 H) 4.31 Cd, J=5.75 Hz, 2 H) 4.36 ( s. 2 H) 6.74 (t. 1 H) 7.19 - 7.40 (m, ί» H) 7.b0 - /.65 (m, 4 H) 8.78 - 8.82 (m, 1 H) 8.86 (s, 2 H MS CESI/APCI Dual): 435 (M+1), 433 (M-1) 100 cycloHexyl ch3 1H NMR (300 MHz, DMSO-D6) dppm 1.07 - 1.40 Cm. 11 H) 1.49 - 1.59 (m, 1 H) 1.60 - 1.73 (m. 2 H) 1.76 - 1.87 (mt 2 H) 3.40 - 3.54 (m, 1 H) 3.63 (s, 3 H) 4.36 (s, 2 H) 6.09 - 6.18 (m, 1 H 7.46 - 7.63 (m, 4 H) 8.46 - 8.50 (m. 1 H) 8.83 - 8.87 (m, 2 H) MS (ESI/APCI Dual): 427 (M+1) 101 PhCH2 H 1H NMR (300 MHz DMSO-D6) 5ppm 1.23 (s, 6 H) 4.16 - 4.41 (m, 4 H) 6.67 - 6.81 (m, 1 H) 7.18 - 7.40 (m, 5 H) 7.48 - 7.66 (m, 4 H) 8.76 - 8.82 (m, 1 H) 8.86 (s, 2 H) 12.24 - 12.55 (br, 1 H) MS (ESI/APCI Dual): 421 (M+1) 102 cycloHexyl H 1H NMR (200 MHz, DMSO-D6 5ppm 1.00- 1.90 Cm, 16 H) 3.40 - 3.58 (m, 1 H) 4.32 (s, 2 H) 6.09 - 6.21 (m, 1 H) 7.40 - 7.67 (m, 4 H) 8.51 (d. 1 H 8.85 (s, 2 H) 12.26 - 12.53 (br, 1 H) MS CESI/APCI Dual): 413 (M+1) °Y%B RA RB 103 2-Me〇-5-Me-Ph H 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.02 - 1.09 Cm, 2 H ) 1.18 -1.25 (m. 2 H) 2.24 (s, 3 H) 3.85 (s, 3 H) 4.44 (s. 2 H) 6.72 - 6.79 (m, 1 H) 6.90 (d. J=8.2 Hz. 1 H) 7.54 - 7.69 (m, 4 H) 7.97 - 8.01 (mT 1 H) 8.21 (s, 1 H) 8.88 (s, 2 H) 9.47 (s, 1 H) 12.36 - 12.53 (br, 1 H) MS (ESI/APCI Dual): 449 (M+1) -269- 200918053 [表bι〇] 〇ίγ°^Β rr°^3 RA RB 104 3-F-4-C 卜Ph ch3 1H NMR (300 MHz , CDCI3) δ ppm 1.90 - 2.21 (m, 4 H) 2.44 - 2.60 (m, 2 H) 3.73 (s, 3 H) 4.62 (s, 2 H) 6.78 - 6.86 (m, 1 H) 7.50 -7.65 ( m, 4 H) 7.66 - 7.75 (m, 3 H) 7.78 (dd. J=8.6. 2.6 Hz, 1 H) 7.83 (s, 1 H) 8.34 - 8.38 (m, 1 H) MS CESI/APCI Dual) : 469 (M+1), 467 (MM) 105 3,4-diEt-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.21 - 1.31 (m. 6 H) 1.89 -2.22 (m, 4 H) 2.44 *- 2.61 (m, 2 H) 2.67 - 2.78 (m, 4 H) 3.73 (s. 3 H) 4.62 (s, 2 H) 6.78 - 6.85 (m, 1 H) 7.26 - 7.30 (m, 1 H) 7.48 -7.56 (m, 2 H) 7.64 (dd, J=7.9, 2.0 Hz. 1 H) 7.69 - 7.82 (m , 4 H) 7.90 (s, 1 H) 8.34 - 8.39 (m, 1 H) MS (ESI/ΑΡΟΪ Dual): 473 (M+1), 471 (M-1) 106 3-Me-4-F- Ph ch3 MS (ESI): 449CM+1), 447CM-1) 107 3-F-4-Me-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.90 - 2.20 (m, 4H) 2.36 (s, 3H 2.47 - 2.60 (m, 2H) 3.73 (s, 3H) 4.63 (s, 2H) 6.82 (d, J=8.4 Hz, 1H) 7.32 (dd, J= 7.5 Hz, 7.8 Hz, 1H) 7.51 - 7.60 ( m. 4H) 7.72 (d, J=8.7 Hz. 2H) 7.76 - 7.82 Cm. 2H) 8.37 (d, J=3.0 Hz, 1H) MS (ES〇: 449 (M+1) 447 (M-1) 108 3-CF3-4-F-Ph ch3 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.83 - 2.20 (m. 4H) 2.35 -2.50 (m, 2H) 3.66 (s, 3H) 4.59 (s, 2H) 6.90 (d, J=9.2 Hz. 1H) 7.71 (d, J=8.6 Hz, 2H) 7.74 (t, J=9.7 Hz, 1H) 7.87 (d, J=8.9 Hz, 2H) 8.03 (dd. J =2.5 Hz, 8.5 Hz. 1H) 8.30 - 8.45 (m. 2H) 8.50 (d. J=3.0 Hz, 1H) 10.58 Cs, 1H) MS(ESI): 503(M+1), 50KM-1) 109 2-F-4-CF3-Ph ch3 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.83 - 2.20 (m, 4H) 2.34 -2.50 (m, 2H) 3.66 (s, 3H) 4.59 (s, 2H) 6.89 (d, J=8.6 Hz, 1H) 7.70 (d. J=8.3 Hz, 2H) 7.76 (d. J=7.7 Hz, 1H) 7.82 (d, J=8.6 Hz, 2H) 7.87 - 7.98 (m. 2H 8.02 (dd, J=2.7 Hz, 8.6 Hz, 1H) 8.49 (d. J=2.4 Hz, 1H) 10.72 (st 1H) MS(ESI): 503(M+1), 50HM-1) 110 3, 5-diF-Ph ch3 1 H NMR ¢300 MHz, DMSO-D6) 6 ppm 1.83 - 2.17 Cm, 4H) 2.35 -2.50 (m, 2H) 3.66 (s. 3H) 4.59 (s. 2H) 6.89 (d, J=8.6 Hz, 1H) 7.51 -7.62 (m, 1H) 7.66 - 7.77 (mt 2H) 7.70 (d, J=8.6 Hz, 2H) 7.88 (d, J=8.6 Hz. 2H) 8.03 (dd, J= 2.4 Hz, 8.6 Hz, 1H) 8.50 (d, J=2.4 Hz, 1H) 10.46 (s, 1H) MS (ESI): 453 (M+1), 45KM-1) 111 ch3 1HNMR (300 MHz.DMSO- D6) 5ppm1.83-2.17(m.4H)2-33-2.50 (m. 2H) 3.66 (s, 3H) 4.59 (s. 2H) 6.89 (d, J=8.6 Hz, 1H) 7.61 (d. J =8.6 Hz, 1H) 7.69 (d. J=8.3 Hz. 2H) 7.83 - 7.95 (m, 3H) 7.98 -8.07 (m, 2H) 8.49 (d, J=2.4 Hz, 1H) 10.39 (s, 1H) MSCESI): 497CM+1), 495CM-1) 112 2-F-3-CF3-Ph ch3 MS (ESI): 503CM+1) 50KM-1) 113 2,3-diF-Ph ch3 MS (ESI): 453CM+1) 45KM-1) 114 2-F-5-CF3-Ph ch3 MS (ESI): 503 (M+1) 50KM-1) 115 3-CF3〇-Ph ch3 1H NMR (300 MHz. CDCI3) (5 ppm 1.90 - 2.20 Cm, 4H) 2.44 -2 59 (m, 2H) 3.73 (s, 3H) 4.62 (s, 2H) 6.82 (d, J=8.3 Hz, 1H) 7.38 -7.45 (m, 1H) 7.50 - 7.58 (m, 3H) 7.67 - 7.82 (m. 5H) 7.85 - 7.91 Cm, 1H) 8.36 (d. J=3.0 Hz, 1H) MS (ESI): 501CM+1), 499(M-1) 116 2 -CI-4,5-diF-Ph ch3 MS (ESI): 487CM+1) 485CM-1; 117 3-CI-4-Me-Ph ch3 1H NMR ¢300 MHz, CDCI3) dppm 1.90 - 2.20 Cm, 4H ) 2.46 Cs, 3H) 2 46 - 2.60 (m. 2H) 3.73 (s, 3H) 4.62 (s, 2H) 6.81 (d. J=8.6 Hz, 1H) 7.36 (d, J=7.7 Hz, 1H) 7.49 - 7.56 (m, 2H) 7.64 - 7.73 (m, 3H) 7.75 - 7.85 (m. 2H) 7.87 (s, lH) S.36 (d. J=2.4 Hz. 1H) MS(ESI): 465CM+1 463CM-1) 118 3-F-Ph ch3 MS(ES!): 435CM+1) 433CM-1) 119 3-CF2HCF20-Ph ch3 1H NMR (300 MHz. CDCI3) δ ppm 1.90 - 2.20 (m, 4H) 2.46 - 2.60 (m. 2H) 3.73 (s. 3H) 4.62 (s, 2H) 5.96 (tt, J=2.8 Hz, 52.9 Hz, 1H) 6.82 (d, J=8.4 Hz, 1H) 7.40 - 7.46 (m, 1H) 7.51 - 7.58 (m. 3H) 7.69 - 7.83 (m. 5H) 7.86 - 7.94 (m. 1H) 8.37 (d. J=2.7 Hz, 1H) -270- 200918053 [Table 1 1] 120 3,4-diMeO-Ph ch3 1H NMR (300 MHz, DMSO-D6) &lt;5 ppm 1.85 - 2.16 (m, 4H) 2.35 - 2.50 (m. 2H) 3.66 (s, 3H) 3.86 (s, 3H) 3.87 (s. 3H) 4.59 (s, 2H) 6.89 (d. J= 8.6 Hz. 1H) 7.11 (d, J=8.6 Hz. 1H) 7.56 (s, 1H) 7.61 -7.71 (m, 1H) 7.68 (d, J=8.6 Hz, 2H) 7.88 (d. J=8.6 Hz, 2H) 8.02 (dd, J=2-8 hlz, 8.8 Hz, 1H) 8.49 (d, J=2.4 HZ, 1H) 10.18 (s, 1H) MS (ESI): 477 (M+U 475 (M-1) 121 3-Me-4-MeO-Ph ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.92 - 2.23 (m, 4H) 2.28 (s, 3H) 2.46 - 2.62 (m. 2H) 3.73 (s, 3H) 3.90 (s. 3H) 4.62 (s, 2H) 6.81 (d, J=8.9 Hz. 1H) 6.89 (d, J=8.3 Hz. 1H) 7.51 (d, J=8.6 Hz, 2H) 7.67 - 7.88 Cm. 6H) 8.36 (d. J=2A Hz, 1H) MS(ESI); 461 (M+l) 459 (M-1) F RA R巳122 3-CI-4-Me-Ph ch3 1H NMR ¢300 MHz , DMSO-D6) ¢5 ppm 1.83 - 2.17 Cm, 4H) 2.34 -2.47 (m. 2H) 2.44 (s. 3H) 3.66 (s, 3H) 4.60 (s, 2H) 6.91 (d, J=8.9 Hz. 1H) 7.51 - 7.59 (m, 2H) 7.62 - 7.73 (m, 2H) 7.89 (dd. J=1.8 Hz, 8.0 Hz, 1H) 8.06 (d, J=1.5 Hz, 1H) 8.09 (dd, J=2.4 Hz. 8.6 Hz, 1H) 8.56 Cd. J=2.1 Hz, 1H) 10.26 (s, 1H) 0 丫. , B RA RB 123 3-CF3-4-CI-Ph ch3 1H NMR ¢300 MHz, CDCI3) 6 ppm 1.03 - 1.12 (m. 2 H) 1.36 -1.44 (m, 2 H) 3.71 (s. 3 H) 4.51 (s, 2 H) 6.84 (d, J=8.4 Hz, 1 H) 7.55 (d, J=8.6 Hz, 2 H) 7.63 - 7.76 (m. 3 H) 7.75 - 7.90 (m, 2 H) 7.96 - 8.06 (m, 1 H) 8.18 - 8.25 Cm, 1 H) 8.32 - 8.40 Cm, 1 H) MS (ESI/APCI Dual): 505 (M+1), 503 (M-1) 124 3-CF30- Ph ch3 MS (ESI): 487CM+1) 485 (M-1) 125 3-Me~4-F-Ph ch3 1H NMR (300 MHz, CDCI3) &lt;5 ppm 1.07 (q, J=3.8 Hz, 2H) 1.39 (q. J=3.8 Hz, 2H) 2.36 (d. J=1.8 Hz, 3H>3.71 (s, 3H) 4.51 (s, 2H) 6.84 (d, J=8.4 Hz, ΊΗ) 7.1 i (dd, J=8.7 Hz, 9.0 Hz, IH) 7.53 (d, J=8.4 Hi 2H) 7.65 - 7.83 (m, 6H) 8.34 (d. J=2.7 Hz_ 1H) MS(ESI): 435 (M+1) 433 (M-1) 126 3—GI-4-Me-Ph ch3 1H NMR (300 MHz, CDCI3) 5ppm 1.07 - 1.14 (m. 2H) 1.21 - 1.27 (m, 2H) 2.42 (s. 3H) 3.62 (s. 3H) 4.42 (s. 2H) 6.91 (d. J=8.9 Hz, 1H) 7.53 (d, J=8.0 Hz, 1H) 7.66 (d, J=8.6 Hz, 2H) 7.83 - 7.90 Cm, 3H) 7.97 - 8.05 (m. 2H) 8.45 Cd, J=3.0 Hz, 1H) 10.36 (s. 1H) MS(ESI): 451CM+1), 449( M-1) 丫, B 七 H RA RB 127 S-CFs+ChPh ch3 1H NMR (300 MHz. CDCI3) &lt;5 ppm 1.33 (s. 6 Hi 3 71 (s. 3 H) 4.38 (s, 2 H) 6.82 (d. J=8.7 Hz, 1 H) 7.55 (d. J=8.6 Hz, 2 H) 7.62 -7.87 (m. 5 H) 7.97 - 8.05 (m. 1 H) 8.22 (d. J=2.3 Hz. 1 H) 8.36 (d, J=2.8 Hz. 1 H) MS (ESI/APCI Dual): 507 (M+1), 505 (M-1) 128 3-Cl-4-Me-Ph ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.34 (s, 6 H) 2.46 (s, 3 H) 3.71 (s 3 H) 4.38 (s. 2 H) 6.82 (d. J=8.6 Hz. 1 H) 7.37 (d, J=8.2 Hz. 1 H) 7.53 (d. J=8.6 Hz, 2 H) 7.62 - 7.76 (m. 3 H) 7.76 - 7.84 (m, 2 H) 7.88 (d. J-1.9 Hz, 1 H) 8.36 (d. J-2.5 Hz, 1 H) MS (ESI/APCI Dual): 453 (M +1), 451 (M-1) -271 - 200918053 [Table 12] 〇γ°&gt;Β H RA RB 129 3-CF3-4-C 卜 Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.96 - 2.13 (m. 2 H) 2.13 -2.27 (m. 2 H) 2.48 - 2.63 (m, 2 H) 3.74 (s. 3 H) 4.69 (s. 2 H) 7.55 (d J=8.6 Hz, 2 H 7.68 Cd, J=8.1 Hz, t H) 7.77 (d, J=8.6 Hz, 2 H) 7.87 - 7.95 Cm, 1 H) 7.99 - 8.07 (m. 1 H) 8.23 (d. J=2.0 Hz. 1 H) 8.72 (s, 2 H) MS CESI/APCI Dual): 520 (M+1), 518CM-1) 130 3-CF3〇-Ph ch3 MS(ESI): 502CM+1) 500(M-1 ) 131 3-Me- 4-F-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.96 - 2.2B (w, 4H) 2.35 (d. J=1.8 Hz. 3H) 2.48 &gt; 2.61 (m. 2H) 3.73 (s. 3H ) 4.68 (s, 2H) 7.10 (dd, J = 8.3 Hz. 8.9 Hz, 1H) 7.51 (d. J=8.9 Hz, 2H) 7.67 - 7.79 (m, 2H) 7.76 (d. J=8.9 Hz. 2H 7.95 (s, 1H) 8.70 (s, 2H) MSCESI): 450 (M+1) 448 (M-1) 132 3-CI-4-Me-Ph ch3 IN NMR (300 MHz, CDCI3) 5ppm 1.95 - 2.25 (m. 4H) 2.46 (s, 3H) 2.49 - 2.61 (m. 2H) 3.73 (s. 3H) 4.69 (s. 2H) 7.36 (d, J=8.3 Hz. 1H) 7.53 (d. J=8.3 Hz. 2H) 7.68 (dd, J=1.8 Hz. 7.7 Hz, 1H) 7.76 Cd. J=8.3 Hz, 2H) 7.84 - 7.90 (m, 2HJ 8.71 (s, 2H) MS(ESI): 466CM+1) 464CM-1) 〇ίγ°&gt;Β RA RB 133 3-CF3-4-Ci-Ph ch3 1H NMR (300 MHz. CDCI3) δ ppm 1.05 - 1.15 (m, 2 H) 1.38 -1.46 (m. 2 H) 3.70 (s. 3 H) 4.58 (s, 2 H) 7.55 Cd, J=8.6 Hz. 2 H) 7.68 (d. J=8.2 Hz. 1 H) 7.77 (d. J=8.6 Hz. 2 H 7.89 (s. 1 H) 8.02 (dd, J=8.6, 2.3 Hz, 1 H) 8.22 (d, J=2.3 Hz, 1 H) 8.71 (s. 2 H) MS CESI/APCI Dual): 506 ( M+1), 504 (M_t) 134 3-CF3〇-Ph ch3 MSCESI): 488(M+1) 486(M-1) 135 3-Me-4-F-Ph ch3 1H NMR C300 MHz. CDCI3) δ ppm 1.10 Cq. J=3.8 Hz, 2H) 1.41 (q. J=3.9 Hz. 2H) 2.36 (s. 3H) 3.70 (s. 3H) 4.57 (s. 2H) 7.11 Cdd. J=8.7 Hz, 8.7 Hz. 1H) 7.52 (d. J=8.4 Hz. 2H) 7.67 - 7.82 (m. 2H) 7.77 (d. J=8.4 Hz, 2H) 7.94 (s, 1H) 8.70 (s, 2H) MSCESI): 436 (M+1) 434 (M-1) 136 3-C Bu 4-Me-Ph ch3 1H NMR (300 MHz, CDCI3) (5 ppm 1.05 - 1.13 (m, 2H) 1.38 -1.45 (m. 2H) 2.46 (sT 3H) 3.70 (s, 3H) 4.57 (s. 2H) 7.36 (d, J=7.7 Hz. 1H) 7.52 (d. J=8.9 Hz. 2H) 7.65 - 7.71 (m, 1H) 7.76 (d. J=8.6 Hz, 2H) 7.83 - 7.91 (m, 2H) 8.70 (s, 2H) MS (ESI): 452CM+1), 450CM-1) H RA RB 137 3-CF3-4 -CI-Ph gh3 1H NMR (300 MHz. CDCI3) ¢5 ppm 1.37 (s, 6 H) 3.71 (s, 3 H) 4.45 (s, 2 H) 7.49 - 7.58 (m. 2 H) 7.67 (d, J=8.4 Hz, 1 H) 7.73 -7.81 (m. 2 H) 7.99 (s. 1 H) 8.03 (dd, J=8.2, 2.2 Hz. 1 H) 8.23 (d. J=2.0 Hz, 1 H) 8.71 (s, 2 H) MS CESI/APCI Dual): 508 (M+1), 506 (M-1) rr. ▽乜H RA RB 138 3,4-diMe-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.91 ~ 2.22 (m, 4 H) 2.28 -2.34 (m. 6 H) 2.46 - 2.62 (nn, 2 H ) 3.73 (s, 3 H) 4.62 (s, 2 H) 6.78 -6.86 Cm, 1 H) 7.49 ~ 7.90 (m, 9 H) 8.37 (d, J=2.5 Hz, 1 H) MS CESI/APCI Dual) : 445 (M+1), 443 (M-1) -272- 200918053 [表卜13] 139 4-F-PhCH2 ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.90 - 2.20 (m. 4 H) 2.45 -2.59 (m, 2 H) 3.72 (s. 3 H) 3.73 (s, 2 H) 4.61 Cs, 2 H) 6.79 (d, J=8.6 Hz, 1 H) 7.04 - 7.15 (m, 2 H) 7.17 (s, 1 H) 7.28 - 7.37 (m, 2 H) 7.41 - 7.55 (m, 4 H) 7.73 (dd, J=8.6, 2.5 Hz. 1 H) 8.32 (d. J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 449 (MM), 447 (M-1) 140 3,4-diCI-Ph ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.90 - 2.23 (m. 4 H) 2.44 -2.62 (m. 2 H) 3.73 (s. 3 H) 4.63 (s. 2 H) 6.75 - 6.87 (m, 1 H) 7.49 ~ 7.62 (m. 3 H) 7.67 - 7.86 (m, 5 H) 8.00 (d J=2.2 Hz. 1 H) 8.32 -8.41 Cm, 1 H) MS (ESI/APCI Dual): 485 (M+1), 483 (Mt) 141 2t3-diMe-Ph ch3 1H NMR ¢300 MHz, CDCI3 δ ppm 1.90 - 2.22 Cm, 4 H) 2.37 (s, 3 H) 2.44 - 2.63 (m. 5 H) 3.73 (s. 3 H) 4.62 (s. 2 H) 6.82 (d, J=8.7 Hz, 1 H) 7.03 - 7.13 (m, 2 H) 7.42 (d. J=7.6 Hz, 1 H) 7.47 - 7.56 (m, 3 H) 7.64 - 7.74 (m, 2 H) 7.78 (dd, J=8.6, 2.5 Hz, 1 H) 8.36 (d, J=2.3 Hz, 1 H) MS (ESI/APCI Dual ): 445 (M+1), 443 (M-1) 142 cycloHexyl ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.15 - 1.43 Cm, 3 H) 1.47 -2.34 (m, 12 H) 2.43 - 2.61 (m 2 H) 3.73 (s, 3 H) 4.61 (s, 2 H) 6.80 (d, J=8.6 Hz. 1 H) 7.19 (s. 1 H) 7.42 - 7.51 (m, 2 H) 7.56 - 7.65 ( m, 2 H) 7.76 (dd, J=8.6, 2.5 Hz, 1 H) 8.33 (d, J=2.5 1 H) MS (ESI/APCI Dual): 423 (M+1) 143 2-naphthyl ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.94 - 2.22 Cm, 4 H) 2.46 -2.61 (m, 2 H) 3.74 (s. 3 H) 4.63 (s. 2 H) 6.79 - 6.87 (m, 1 H) 7.52 - 7.67 (m, 4 H) 7.74 - 8.14 (m. 7 H) 8.36 - 8.46 (m, 2 H) 8.67 -8.72 (m. 1 H) MS (ESI/APCI Dual): 467 (M+1). 465 (M-1) 144 3-CI-4-F-Ph ch3 1H NMR (300 MHz, CDCI3) ¢5 ppm 1.93 - 2.22 Cm, 4 H) 2.46 -2.60 (m, 2 H) 3.73 (s. 3 H ) 4.63 (s. 2 H) 6.82 (d, J=8.6 Hz, 1 H) 7.23 - 7.32 (m, 1 H) 7.50 - 7.58 (m, 2 H) 7.65 - 7.84 (m, 5 H) 7.98 (dd, J=6.9. 2.3 Hz, 1 H) 8.37 (d, J=2.6 Hz, 1 H) MS (ESI/APCI Dual): 469 (M+1). 467 (M-1) 145 Ph ch3 1H NMR (300 MHz. CDCI3) 6 ppm 1.90 - 2.21 (m, 4 H) 2.46 -2.61 (m. 2 H) 3.73 (s. 3 H) 4.63 (s, 2 H) 6.78 - 6.86 (m, 1 H) 7.47 -7.62 Cm, 5 H) 7.69 - 7.94 (m, 6 H) 8.37 Cdd, J=2.6, 0.7Hz, 1 H) MS (ESI/APCI Dual): 417 (M +1), 415 (M-1) 146 4-Et-Ph ch3 1H NMR (300 MHz, CDC13) S ppm 1.28 (t, J=7.5 Hz, 3 H) 1.90 -2.22 (m. 4 H) 2.45 - 2.62 (m. 2 H) 2.74 (q, J=7.7 Hz. 2 H) 3.73 (s. 3 H) 4.63 (s, 2 H) 6.78 - 6.85 (m. 1 H) 7.30 - 7.37 (m, 2 H 7.49 -7.57 (m, 2 H) 7.68 - 7.87 (m, 6 H) 8.33 - 8.40 Cm. 1 H) MS (ESI/APCI Dual): 445 (M+1), 443 (M-1) 147 3 -CF3-4-Me-Ph ch3 1H NMR ¢300 MHz, CDCI3) 6 ppm 1.89 - 2.23 Cm. 4 H) 2.44 -2.64 (m, 5 H) 3.73 (s. 3 H) 4.63 (s. 2 H) 6.82 (d, J=8.6 Hz. 1 H) 7.44 (d. J=8.2 Hz. t H) 7.51 - 7.58 (m. 2 H) 7.69 - 7.76 (m. 2 H) 7.79 (dd. J=8.5, 2.6 Hz, 1 H) 7.89 (s, 1 H) 7.92 - 7.99 (m. 1 H) 8.11 - 8.16 (m. 1 H) 8.37 (d. J=2.2 Hz, 1 H) MS (ESI/APCI D Ual): 499 (M+1). 497 (M-1) 148 3-F-4-CFa-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.93 - 2.20 (m, 4H) 2.46 -2.59 (m 2H) 3.73 (s, 3H) 4.63 (s, 2H) 6.79 - 6.85 (dd, J=0.9 Hz, 8.4 Hz. 1H) 7.55 (d, J=8.7 Hz, 2H) 7.68 - 7.81 (m. 6H) 7.85 - 7.90 Cbr, 1H) 8.34 - 8.38 Cm, 1H) MSCESI): 503tM+1), 50KM-1) 149 3-CI-Ph ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.91-2.20 (m. 4H ) 2.48 - 2.60 (m. 2H) 3.73 (s. 3H) 4.63 (s, 2H) 6.82 (d, J=8.4 Hz. 1H) 7.45 (dd. J=7.5 Hz, 8.1 Hz, 1H) 7.51- 7.57 ( m. 3H) 7.72 (d, J=8.7 Hz, 2H) 7.75 - 7.82 (m, 2H) 7.84 (s, 1H) 7.87 - 7.90 (m. 1H) 8.37 (d, J=2.4 Hz, 1H) MSCESI) : 451 (M+1) 449 (M-1) 150 3-CF3-Ph ch3 1H NMR (300 MHz. CDCI3) 5 ppm 1.90 - 2.21 Cm, 4H) 2.45 - 2.60 (m, 2H) 3.73 (s, 3H 4.63 (s. 2H) 6.82 (d. J=8.7 Hz. 1H) 7.55 (d. J=8.4 Hz. 2H) 7.66 (t, J=7.5 Hz, 1H) 7.70 - 7.93 (m. 5H) 8.09 ( d, J-7.5 Hz. 1H) 8 16 (s. 1H) 8.38 (s. 1H) MS(ESI): 485CM+1), 483(M-1) 151 2-CF3-4-F-Ph ch3 1H NMR (300 MHz. CDCI3) 5ppm 1.90 - 2.20 Cm. 4H) 2.43 -2.59 (m, 2H) 3.73 (s, -3H) 4.62 (s. 2H) 6.82 (d, J=8.7 Hz. 1H) 7.31 -7.40 (m, 1H) 7.43 - 7.56 (m. 3H) 7.64 - 7.75 (m. 4H) 7.78 (dd, J=2.6 Hz, 8.9 Hz, 1H) 8.36 Cd, J=2.4 Hz. 1H) MSCESI): 503CM+1). 50ΗΜ-Ί) -273- 200918053 [表卜14] 152 3,5-diCI-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.90 - 2.20 Cm, 4H) 2.46 - 2.60 (m, 2H) 3.73 (s, 3H) 4.62 (s. 2H) 6.81 (d. J=8.3 Hz. 1H) 7.49 -7.57 (m, 3H) 7.69 (d, J =8.3 Hz. 2H) 7.75 (d, J=2.1 Hz, 2H) 7.78 Cd, J=2.4 Hz. 1H) 7.83 - 7.91 (br, 1H) 8.35 (d, J=2.4 Hz, 1H) 153 2,5 -diF-Ph ch3 1H NMR ¢300 MHz, CDCI3) (5 ppm 1.90 - 2.20 Cm. 4H) 2.47 -2.60 (m, 2H) 3.73 (s,3H) 4.62 (s. 2H) 6.82 (d. J=8.9 Hz. 1H) 7.13 -7.27 (m. 2H) 7.54 (d. J=8.6 Hz. 2H) 7.74 (d, J=8.6 Hz, 2H) 7.78 (dd. J=2.4 Hz. 8.3 Hz. 1H) 7.85 - 7.94 (m. 1H) 8.37 (dr J=2.4 Hz, 1H) 8.51 (d. J=15.8 Hz, 1H) MSCESI): 453(M+1), 451CM-1) 154 2,4-diF-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.91 - 2.20 (m, 4H) 2.48 -2.62 (m, 2H) 3.73 (sT 3H) 4.62 (sT 2H) 6.81 (d, J=8.6 Hz, 1H) 6.90 -7.00 (mt 1H) 7.03 - 7.11 (m, 1H) 7.53 (d, J=8.6 Hz, 2H) 7.73 (d. J=8.6 Hz, 2H) 7.78 (dd. J=2.4 Hz, 8.6 Hz. 1H) 8.23 (d, J=6.6 Hz, 8.9 Hz. 1H) 8.33 - 8.46 (m, 2H) MS (ESI): 453CM+1), 451CM-1) 155 3,4-diF-Ph ch3 1H NMR (300 MHz. DMSO-D6) 5ppm 1.83 - 2.17 Cm. 4H) 2.32 -2.50 (m. 2H) 3.66 ( s. 3H) 4.59 (s, 2H) 6.89 (d, J=8.3 Hz, 1H) 7.58 -7.74 (m, 1H) 7.69 (d, J=8.6 Hz. 2H) 7.82 - 7.94 (m. 1H) 7.87 ( d, J=8.3 Hz. 2H) 7.99 - 8.13 (m. 1H) 8.02 (dd, J=2.5 Hz, 8.5 Hz, 1H) 8.49 (d. J=2.4 Hz, 1H) 10.42 (s. 1H) MS ( ESI): 453CM+1), 45KM-1) 156 4-CF3〇-Ph ch3 1H NMR (300 MHz, CDCI3) 6ppm 1.90 - 2.20 (m, 4H) 2.49 -2.61 (m, 2H) 3.73 (s, 3H 4.62 (s, 2H) 6.81 (d. J=8.5 Hz. 1H) 7.33 (d. J=8.2 Hz. 2H) 7.53 (d. J=8.5 Hz, 2H) 7.71 (d, J=8.5 Hz, 2H 7.77 (dd, J=2.7 Hz. 8.5 Hz, 1H) 7.89 (s. 1H) 7.94 (d. J=8.8 Hz, 2H) 8.36 (d, J=2.4 Hz. 1H) MSCESI): 50KM+1) 499CM-1) 157 3-MeO - Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.92 - 2.20 Cm, 4H) 2.46 - 2.60 (m, 2H) 3.73 Cs. 3H) 3.89 (s. 3H) 4.62 Cs , 2H) 6.82 (d, J=8.7 Hz, 1H) 7.06 - 7.14 (m, 1H) 7.37 - 7.44 (m, 2H) 7.45 - 7.48 (m. 1H) 7.53 (d, J=8.5 Hz. 2H) 7.73 (d. J=8.8 Hz. 2H) 7.79 (dd. J=2.5 H MS(ESI): 447 (M+1) 445 ( M-1) 158 3-Me-Ph ch3 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.83 - 2.18 (m, 4H) 2.32 - 2.50 (m. 2H) 2.43 (s, 3H) 3.66 (s. 3H) 4.59 (s, 2H) 6.89 (d. J=8.6 Hz. 1H) 7.38 - 7.53 (m, 2H) 7.67 (d, J=8.6 Hz, 2H) 7.72 - 7.85 (m, 2H) 7.89 (d. J=8.3 Hz, 2H) 8.02 (dd. J=2.4 Hz, 8.6 Hz. 1H) 8.49 (d, J=2.4 Hz, 1H) 10.31 Cs, 1H) MStESI): 43KM+1). 429CM-1) H RA RB 159 3-CF3-Ph ch3 MS (ESI): 503 (M+1) 50KM-1).丫0, e F RA RB 160 3-CF3-Ph ch3 1H NMR (300 MH2. CDCI3) 5 叩阳1.91-2.21 (阳.4屮2.48-2.61 (m, 2H) 3.73 (s. 3H) 4.63 (s 2H) 6.83 (dr J=8.7 Hz. 1H) 7.28 -7.41 (m. 2H) 7.67 (t, J=8.0 Hz, 1H) 7.77 (dd. J=2.6 Hz, 8.9 Hz. 1H) 7.85 (d. J=7.8 Hz, 1H) 8.08 (d, J=4.8 Hz, 2H) 8.18 (s. 1H) 8.36 (d. J=3.0 Hz, 1H) 8.50 (t, J= 8.4 Hz, 1H) MS (ESI) : 503CM+1), 501CM-1) v°&gt;= XXT^ KA' -V - RA RB 161 3,4-diCI-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.01 - 1.12 Cm, 2 H ) 1.34 -1.44 (m. 2 H) 3.72 (s, 3 H) 4.51 (s. 2 H) 6.80 - 6.87 (m. 1 H) 7.49 -7.62 (m. 3 H) 7.66 - 7.85 (m. 5 H) 7.94 - 8.04 (m, 1 H) 8.28 -8.39 (m, 1 H) MS (ESI/APCI Dual): 471 (M+1). 469 (M-1) -274- 200918053 [表卜15] 162 3,4-diMe-Ph ch3 1H NMR (300 MHz. CDCI3) δ ppm 1.03 - 1.10 (m, 2 H) 1.35 -1.42 (m. 2 H) 2.34 (s, 3 H) 2.36 (s, 3 H) 3.72 (s, 3 H) 4.51 (s. 2 H) 6.84 (d, J=9.0 Hz, 1 H) 7.48 - 7.86 (m, 8 H) 8.34 (d, J=2.2 Hz, 1 H) MS (ESI /APCI Dual): 431 (M+1) 163 3-C!-4-F-Ph gh3 1H NMR ¢300 MHz, CDCI3) 6 Ppm 1.02 - U1 (m, 2 H) 1.35 -1.43 (m, 2 H) 3.72 (s, 3 H) 4.51 (s. 2 H) 6.84 (d, J=7.9 Hz, 1 H) 7.22 - 7.33 (m , 1 H) 7.54 (d, J=8.6 Hz, 2 H) 7.66 - 7.85 (m, 5 H) 7.95 - 8.02 Cm, 1 H) 8.30 - 8.37 (m. 1 H) MS (ESI/APCI Dual): 455 (M+1), 453 (M-1) 164 3-CF3-Ph ch3 1H NMR (300 MHz, CDCI3) fippm 1.07 (dd, J=4.2 Hz, 7.2 Hz. 2H) 1.39 (dd. J=4.2 Hz, 7.2 Hz, 2H) 3.72 (s. 3H) 4.51 (s, 2H) 6.84 (d, J=8.4 Hz, 1H) 7.55 (d, J=8.4 Hz, 2H) 7.62 - 7.85 (m. 5H) 7.91 Cs, 1H) 8.09 (d. J=8.1 Hz. 1H) 8.15 Cs, 1HJ 8.35 (d, J=2.4 Hz, 1H) MS(ESI): 471 (M+1), 469CM-1) °Y^&gt ; B JUT&quot; H RA RB 165 3-CF3 - Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.65 - 1.86 (m, 6H) 2.08 -2.26 (m, 2H) 3.72 (s. 3H) 4.44 (s. 2H) 6.82 (d, J=8.3 Hz, 1H) 7.55 (d. J=8.6 Hz. 2H) 7.67 (dd, J=7.5 Hz, 8.3 Hz, 1H) 7.74 (d, J=8.6 Hz, 2H) 7.79 (dd, J=2.4 Hz, 8.6 Hz. 1H) 7.84 (d, J=8.0 Hz, 1H) 7.89 (s, 1H) 8.10 (d, J=7.7 Hz. 1H) 8.16 (s, 1H) 8.36 (d , J=2.7 Hz. 1H) MS(ESI): 499 (M+1) 497 (M-1) °Y%B 0 ^XX - H RA RB 166 3,4-d iCI-Ph ch3 1H NMR (300 MHz, CDCI3) ¢5 ppm 1.34 (s. 6 H) 3.71 is. 3 H) 4.39 (s, 2 H) 6.84 (d, J=8.1 Hz, 1 H) 7.49 - 7.64 (m, 3 H) 7.66 -7.78 (m, 3 H) 7.78 - 7.86 (m, 2 H) 8.00 (d, J=2.0 Hz. 1 H) 8.36 (d. J=2.3 Hz. 1 H) MS ( ESI/APCI Dual): 473 (M+1). 471 (M-1) 167 3-CF3-Ph ch3 1H NMR ¢300 MHz, CDCI3) 5 ppm 1.34 (s, 6 H) 3.71 (s, 3 H) 4.39 (s, 2 H) 6.83 (d, J=8.6 Hz, 1 H) 7.49 - 7.95 (m, 8 H) 8.09 (d. J=7.6 Hz, 1 H) 8.16 (s, 1 H) 8.37 (d , J=2.6 Hz, 1 H) MS (ESI/APCI Dual): 473 (M+1), 471 (M-1) 168 3-CF3〇-Ph ch3 1H NMR ¢300 MHz, CDCI3) $ ppm 1.33 ( s, 6 H) 3.71 (s, 3 H) 4.38 (s, 2 H) 6.82 (d. J=8.6 Hz, 1 H) 7.39 - 7.47 (m. 1 H) 7.50 -7.61 (m, 3 H) 7.68 - 7.90 (m. 6 H) 8.36 (d. J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 489 (M+1), 487 (M-1) °^°&gt;B RA〆 v RA RB 169 3,4-diCI-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.97 - 2.13 (m, 2 H) 2.13 -2.29 (m, 2 H) 2.48 - 2.63 (m, 2 H) 3.74 (s, 3 H) 4.69 (s, 2 H) 7.50 -7.65 (m, 3 H) 7.68 - 7.83 (m, 4 H) 8.00 (d. J=2.〇Hz, 1 H) 8.72 Cs, 2 H) MS (ESI/APCI Dual): 486 (M+1), 484 (M-1) 170 3-CI-4-F-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.96 - 2.14 (m 2 H) 2.14 -2.28 (m, 2 H) 2.48 - 2.62 (m. 2 H) 3.74 (s, 3 H) 4.69 (s. 2 H) 7.24 -7.34 (Γη,1Η) 7.50 - 7.59 (Γη, 2Η)7.71-·7.89(〇ί.4Η)7.95-8.02 Cm, 1 H) 8.71 (ε, 2 H) MS (ESI/APCI Dual): 470 (M+1), 468 (M-1) 171 3 ,4-diMe-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.93 - 2.28 (m, 4 H) 2.34 (s, 3 H) 2.36 (s, 3 H) 2.45 - 2.64 (m, 2 H) 3.74 (s. 3 H) 4.69 (s. 2 H) 7.21 - 7.31 (m, 1 H) 7.48 - 7.58 (m, 2 H) 7.58 - 7.66 (m, 1 H) 7.66 - 7.73 (m, 1 H) 7.73 - 7.83 (m, 2 H) 7.88 (s. 1 H) 8.71 (s. 2 H) MS (ESI/APCI Dual): 446 (M+1), 444 (M-1) -275- 200918053 [Table 1 -16] 丫明r RA RB 172 3-CF3-Ph ch3 1H NMR ¢300 MHz, CDCI3) (5 ppm 1.95 ~ 2.29 (m, 4 H) 2.47 -2.63 (m, 2 H) 3.74 (s, 3 H ) 4.70 (s, 2 H) 7.30 - 7.45 (m, 2 H) 7.64 -7.75 (m, 1 H) 7.87 (d, J=7.9 Hz, 1 Η) B.05 - 8.16 (m, 2 H) 8.16 -8.23 (m, 1 H) 8.53 - 8.64 (m, 1 H) 8.72 (s, 2 H) MS CESI/APCI Dual): 504 (M+1), 502 (M-1) 〇ίγ°, Β λ^ν RA RB 173 3-CF3-Ph ch3 1H NMR (300 MHz, CDCI3) i5 ppm 1.96 - 2.33 Cm, 4H) 2.46 -2.61 (m, 2H) 3.73 (s , 3H) 4.69 (s. 2H) 7.54 (d, J=8.7 Hz, 2H) 7.66 (t, J=7.8 Hz, 1H) 7.79 (d, J=8.7 Hz, 2H) 7.84 (d, J=8.4 Hz , 1H) 8.05 - 8.18 (m, 3H) 8.71 (s, 2H) MS (ESI): 486CM+1J, 484 (M-1) 〇Y%BM RA RB 174 3,4-diCI-Ph ch3 1H NMR ( 300 MHz. CDCI3) δ ppm 1.07 - 1.13 Cm, 2 HJ 1.39 -1.45 (m, 2 H) 3.70 (s, 3 H) 4.57 (s, 2 H) 7.50 - 7.63 (m, 3 H) 7.70 -7.79 ( m. 3 H) 7.87 (s, 1 H) 8.00 (d, J=2.0 Hz, 1 H) 8.71 (st 2 H) MS (ESI/APCI Dual): 472 CM+1). 470 (M-1) 175 3-CI-4-F-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.05 - 1.13 Cm, 2 H) 1.38 -1.45 (m. 2 H) 3.70 (s. 3 H) 4.57 (s, 2 H) 7.24 - 7.32 (m. 1 H) 7.50 -7.57 (m, 2 H) 7.71 - 7.85 (m, 3 H) 7.89 (s. 1 H) 7.99 (dd, J=6.9, 2.3 Hz, 1 H) 8.70 (s, 2 H) MS CESI/APCI Dual): 456 (M+1), 454 (M-1) 176 3,4-diMe-Ph ch3 1H NMR (300 MHz, CDCt3) δ ppm 1.07 - 1.13 ( m, 2 H) 1.38 -1.45 (m, 2 H) 2.35 (s, 3 H) 2.36 (s, 3 H) 3.70 (s, 3 H) 4.57 (s, 2 H) 7.23 - 7.29 (m, 1 H) 7.49 - 7.56 (m, 2 H) 7.58 - 7.64 (m. 1 H) 7.66 - 7.70 (m, 1 H) 7.75 - 7.8T (m, 2 H) 7.87 (s, 1 H) 8.71 (s. 2 H) MS (ESI/APCI Dual): 432 CM+1). 430 CM~1) 177 3-CF3-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.10 (dd. J=4.2 Hz. 7.2 Hz. 2H) 1.42 (dd, J=4.2 Hz. 7.2 Hz. 2H) 3.70 (s, 3H) 4.57 (s, 2H) 7.55 (d. J=8.4 Hz, 2H) 7.67 (t, J=7.8 Hz, 1H) 7.79 (d. J=8.7 Hz. 2H) 7.84 (d, J=8.1 Hz, 1H) 8.00 (s. 1H) 8.10 (dt J = 7.5 Hz, 1H) 8.16 (s. 1H) 8.71 Cs, 2H) MSCESI): 472CM+1), 470(M-1) °Y°&gt;B 〇RA RB 178 3-CF3-Ph ch3 1H NMR C300 MHz, CDCI3) δ ppm 1.65 - 1.90 (m, 6H) 2.12 -2.24 (m, 2H) 3.71 (s, 3H) 4.51 (s, 2H) 7.55 (d, J=8.4 Hz, 2H) 7.67 (dd, J =7.5 Hz, 7.8 Hz, 1H) 7.79 (d, J=8.4 Hz, 2H) 7.85 (d, J=7.8 Hz, 1H) 7.91 (s, 1H) 8.10 (d, J=8.1 Hz, 1H) 8.16 ( s. 1H) 8.71 (s. 2H) MSCESI): 500 (M+1) 498 (M-1) 0 丫〇, e, CH' RA RB 179 3,4-diCI-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.37 (s, 6 H) 3.71 (s, 3 H) 4.45 (s, 2 H) 7.49 - 7.63 (m, 3 H) 7 .69 - 7.80 (m, 3 H) 7.89 (s. 1 H) 8.00 (d, J=2.2 Hz, 1 H) 8.70 (s, 2 H) MS (ESI/APCI Dual): 474 (M+1) , 472 (M-1) -276- 200918053 [Table 1-17] 180 3-CF3-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.37 (s, 6 H) 3.71 (s, 3 H) 4.45 ( s, 2 H) 7.50 - 7.57 (m, 2 H) 7.61 - 7.70 Cm, 1 H) 7.75 -* 7.86 (m, 3 H) 8.06 - 8.18 (m, 3 H) 8.70 (s. 2 H) MS CESI /APCI Dual): 474 (M+1). 472 (M-1) 181 3 - CF3〇-Ph ch3 1H NMR (300 MHz. CDCI3) d ppm 1.37 (s. 6 H) 3.71 (s, 3 H) 4.45 (s. 2 H) 7.39 - 7.60 (m. 4 H) 7.73 - 7.85 (m. 4 H) 7.94 (s. 1 H) 8.71 Cs, 2 H) MS (ESI/APCI Dual): 490 (M+ 1), 488 (M-1) H RA RB 182 3-MeS02-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.92 - 2.22 Cm, 4 H) 2.45 -2.60 (m, 2 H) 3.13 (s, (3. 8.10 - 8.16 (m. 1 H) 8.22 - 8.28 (m, 1 H) 8.36 - 8.39 (m, 1 H) 8.41 - 8.44 (m. 1 H) MS (ESI/APCI Dual): 495 (M+1) ), 493 (M-1) 183 2,4-diMe-Ph ch3 1H NMR C300 MHz, CDCI3) δ ppm 1.90 - 2.21 Cm, 4 H) 2.34 (s. 3 H) 2.40 (s, 3 H) 2.45 - 2.62 (m, 2 H) 3.73 (s, 3 H) 4.63 (s, 2 H) 6.82 (d, J=8.6 Hz, 1 H) 7.14 - 7.22 (mt 1 H) 7.23 - 7.37 (m, 1 H) 7.45 - 7.59 (m. 3 H) 7.66 - 7.83 (m, 3 H) 8.36 (d. J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 445 (M+1). 443 (M-1) 184 2,5-diMe-Ph ch3 ΊΗ NMR (300 MHz. CDCI3) δ ppm 1.S9 - 2.21 (m, 4 H) 2.37 (s, 3 H) 2.42 - 2.62 (m. 5 H) 3.73 (s, 3 H) 4.62 (s. 2 H) 6.82 (d, J=8.6 Hz, 1 H) 7.11 - 7.23 (m, 2 H) 7.29 - 7.36 (m, 1 H) 7.46 - 7.58 (m, 3 H) 7.65 - 7.75 (m, 2 H) 7.78 (dd. J=8.7. 2.5 Hz. 1 H) 8.36 (d, J=2.5 Hz) , 1 H) MS (ESI/APCI Dual): 445 (M+1), 443 (M-1) 185 3-Ph-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.89 - 2.23 (m. 4 H 2.43 -2.61 (m. 2 H) 3.73 (s, 3 H) 4.62 (s, 2 H) 6.82 (d, J=8.7 Hz, 1 H) 7.35 - 7.67 (m, 9 H) 7.70 - 7.88 (m , 4 H) 8.01 (s, 1 Η) 8.Π (t, J=1.7 Hz, 1 H) 8.37 (d, J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 493 (M+1 491 (M-1) 186 3,5-diMe-Ph ch3 1H NMR (300 MHz, CDCI3) (5 ppm 1.90 - 2.25 (m. 4 H) 2.41 (s, 6 H) 2.44 - 2.63 Cm, 2 H) 3.73 (s, 3 H) 4.62 (s, 2 H) 6.82 (d, J=9.0 Hz. 1 H) 7.20 (s. 1 H) 7.44 - 7.59 (m, 4 H) 7.68 - 7.89 (m. 4 H) 8.37 (d , J=2.6 Hz, 1 H) MS (ES1/AP01 Dual): 445 (M+1), 443 (M-1) 187 2,6-diMe—Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.92 - 2.21 Cm, 4 H) 2.41 (s, 6 H) 2.45 - 2.63 (mT 2 H) 3.73 (s, 3 H) 4.62 (s, 2 H) 6.82 (d, J=8.6 Hz, 1 H) 7.06 - 7.12 (m. 2 H) 7.19 - 7.24 (m, 1 H) 7.39 (s. 1 H) 7.50 - 7.57 (m, 2 H) 7.69 - 7.75 (m. 2 H) 7.78 (dd. J=8.6, 2.6 Hz. 1 H) 8.34 - 8.38 (m, 1 H) MS (ESI/APCI Dual): 445 (M+1), 443 (M-1) 188 3-F - 4-MeO-Ph ch3 1H NMR (300 MHz, CDCI3) &lt;5 ppm 1.89 - 2.21 (m, 4 H) 2.44 - 2.61 (mt 2 H) 3.73 (s. 3 H) 3.97 (s. 3 H) 4.62 (s, 2 H) 6.82 (d. J=8.7 Hz , 1 H) 7.05 (t. J=8.2 Hz, 1 H) 7.47 - 7.57 (m, 2 H) 7.61 - 7.75 Cm, 4 H) 7.74 - 7.82 (m. 2 H) 8.37 Cm, 1 H) MS ( ESI/APCI Dual): 465 (M+1). 463 (M-1) 189 3_MeO - 4-Me_Ph ch3 1H NMR (300 MHz. CDCI3) δ ppm 1.91 - 2.24 Cm, 4 H) 2.29 (s, 3 H ) 2.44 - 2.62 (m, 2 H) 3.74 (s, 3 H) 3.93 (s, 3 H) 4.74 (s, 2 H) 6.95 (d, J=8.7 Hz, 1 H) 7.16 - 7.36 (m, 2 H) 7.43 - 7.59 (m, 3 H) 7.73 - 7.82 (m. 2 H) 7.90 - 8.07 (m, 2 H) 8.40 (d, J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 461 (M+1), 459 (M-1) 190 3—C Bu 4-MeO-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.89 - 2.23 (m, 4 H) 2.45 -2.61 (m. 2 H 3 73 Cs. 3 H) 3.98 (s, 3 H) 4.67 (s. 2 H) 6.86 (d. J=8 6 Hz. 1 H) 6.98 - 7.07 (m, 1 H) 7.53 (d, J= 8.6 Hz 2 H) 7.73 (d, J=8.6 Hz. 2 H) 7.78 - 7.90 (m, 3 H) 7.94 (d, J-2.2 Hz, 1 H) 8.38 (d, J=2.2 Hz, 1 H) MS (ESI/APCI Dual): 481 (M+1). 479 (M-1) 191 3-Me-4-CI-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.89 - 2.22 (m, 4 H) 2.42 -2.61 (m, 5 H) 3.73 (s. 3 H) 4.63 (s, 2 H) 6.82 (d, J=9.0 Hz, 1 H) 7.43 - 7.84 (m, 9 H) 8.37 (d, J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 465 (M+1). 463 (M-1) -277- 200918053 [Table 1_18] 192 ca ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.78 - 1.90 (m, 4 H) 1.91 -2.21 (m. 4 H) 2.44 - 2.61 (m, 2 H) 2.78 - 2.90 (m, 4 H) 3.73 (s, 3 H) 4.63 (s, 2 H) 6.79 - 6.85 (m, 1 H) 7.16 - 7.22 (m, 1 H) 7.49 -7.63 (m, 4 H) 7.69 - 7.85 (m, 4 H) 8.35 - 8.39 (m, 1 H) MS (ESI/APC丨Dual): 471 (M+1) 193 3-AcO-Ph ch3 1H NMR ¢300 MHz. CDC13) δ ppm 1.91 - 2.21 (m. 4 H) 2.35 (s. 3 H) 2.46 - 2.60 (m, 2 H) 3.73 Cst 3 H) 4.63 (s, 2 H) 6.82 (dd, J=8.6, 0.7 Hz. 1 H) 7.28 -* 7.33 (m. 1 H) 7.48 - 7.57 (m. 3 H) 7.61 -7.65 (m, 1 H) 7.68 - 7.74 (m, 3 H) 7.79 (dd, J=8.6, 2.6 Hz. 1 H) 7.87 (s, 1 H) 8.35 - 8.39 (m, 1 H) MS (ESI/APC丨Dual): 475 (M+1), 473 (M-1) 194 3 - iPr—Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.29 (s, 3 H) 1.32 Cs, 3 H) 1.90 - 2.22 (mT 4 H) 2.46 - 2.61 (m, 2 H) 3.01 (m, 1 H) 3.73 (s, 3 H) 4.63 (s, 2 H) 6.79 - 6.86 (m, 1 H) 7.40 ~ 7.47 (m, 2 H) 7.50 -7.57 (m. 2 H) 7.62 - 7.82 (m, 5 H) 7.88 (s, 1 H) 8.35 - 8.39 ( Mt 1 H) MS (ESI/APCI Dual): 459 (M+1) 195 3-MeS-Ph ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.90 - 2.22 (m. 4 H) 2.45 -2.61 (m. 5 H) 3.73 (s, 3 H) 4.63 (s, 2 H) 6.82 (d, J=8.6 Hz, 1 H) 7.36 - 7.47 (m, 2 H) 7.50 - 7.63 (m, 3 H) 7.68 - 7.87 (m, 5 H) 8.37 (d, J=2.3 Hz, 1 H) MS (ESI/APCI Dual): 463 (M+1), 461 (Mt) 196 3-CF3-4-C 卜 Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.89 - 2.22 Cm, 4 H) 2.44 - 2.60 (m, 2 H) 3.73 (s. 3 H) 4.63 (s. 2 H) 6.79 - 6.86 (m, 1 H) 7.50 - 7.57 (m, 2 H) 7.62 - 7.75 (m. 3 H) 7.78 (dd, J=8.6. 2.6 Hz, 1 H) 7.95 (s, 1 H) 8.01 (dd, J=8.3. 2.3 Hz, 1 H 8.22 (d, J=2.2 Hz. 1 H) 8.35 - 8.38 (m, 1 H) MS (ESI/APCI Dual): 519 (M+1), 517 (M-1) 197 3-CN-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.89 - 2.22 (m, 4 H) 2.43 -2.62 (m, 2 H) 3.73 (s, 3 H) 4.63 (s. 2 H) 6.79 - 6.86 (m, 1 H 7.50 -7.59 (m, 2 H) 7.62 - 7.76 (m, 3 H) 7.79 (dd. J=8.6. 2.5 Hz, 1 H) 7.83 - 7.89 (m. 1 H) 7.92 (s. 1 H) 8.11 - 8.18 (m, 1 H) 8.18 - 8.23 (m, 1 H) 8.34 - 8.39 (m, 1 H) MS (ESI/APCI Dual): 442 (M+1 ), 440 (M-1) 丫, RB RA RB 198 3,5-diMe-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.04 - 1.10 (m, 2 H) 1.35 -1.42 (m, 2 H) 2.40 (s 6 H) 3.71 (s. 3 H) 4.51 (s. 2 H) 6.81 - 6.86 (m, 1 H) 7.17 - 7.21 (m, 1 H) 7.47 - 7.56 (m. 4 H) 7.70 - 7.76 (m , 2 H) 7.79 (dd, J=8.6, 2.5 Hz, 1 H) 7.84 (s, 1 H) 8.33 - 8.35 (m, 1 H) MS (ESI/APCI Dual): 431 (M+1), 429 (M-1) 199 oo* ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.03 - 1.10 Cm, 2 H) 1.35 -1.42 (m. 2 H) 1.75 - 1.91 (m. 4 H) 2.71 - 2.93 (m 4 H) 3.71 (s, 3 H) 4.51 (s, 2 H) 6.83 (d, J=8.6 Hz, 1 H) 7.18 (d, J=7.6 Hz, 1 H) 7.44 - 7.65 (m, 4 H 7.67 - 7.89 Cm, 4 H) 8.26 - 8.43 (m. 1 H) MS (ESI/APCI Dual): 457 (M+1). 455 (M-1) 200 3HPr-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.04 - 1.10 (m, 2 H) 1.29 (s, 3 H) 1.32 (s, 3 H) 1.36 - 1.42 (m. 2 H) 3.01 (m, 1 H) 3.72 (s, 3 H) 4.51 (s. 2 H) 6.84 (d. J=8.6 Hz, 1 H) 7.41 - 7.46 (m, 2 H) 7.50 -7.57 Cm, 2 H) 7.63 - 7.89 Cm, 6 H) 8.33 - 8.36 (m. 1 H) MS (ESI/APCI Dual): 445 (M+1), 443 (M-1) 201 3-CI - 4-MeO-Ph Ch3 1H NMR C300 MHz, CDC!3) δ ppm 0.99 - 1.13 (m, 2 H) 1.35 ~ 1.44 (m, 2 H) 3.72 (s. 3 H) 3.99 (s. 3 H) 4.54 (s. 2 H 6.87 (d, J=8.7 Hz, 1 H) 7.03 (d. J=8.6 Hz, 1 H) 7.49 - 7.59 (m, 2 H) 7.67 -7.79 (m, 3 H) 7.83 (dd, J=8.6 , 2.0 Hz, 2 H) 7.91 - 7.96 (m, 1 H) 8.36 (d, J=2.3 Hz. 1 H) MS (ESI/APCI Dual): 467 (M+1), 465 (M-1) 丫, H RA RB 202 3,5-diMe-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.95 - 2.28 (m, 4 H) 2.41 (s. 6 H) 2.46 - 2.64 (m, 2 H) 3.74 ( s, 3 H) 4.69 (s, 2 H) 7.17 - 7.24 (m. 1 H) 7.44 - 7.58 (m, 4 H) 7.73 - 7.83 (m, 2 H) 7.88 (s, 1 H) 8.71 Cs, 2 H) MS (ESI/APCI Dual): 446 (M+1), 444 (M-1) -278- 200918053 [Table 19] 203 οα ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.76 - 1.91 (m , 4 H) 1.93 -2.27 (m, 4 H) 2.47 - 2.62 (m, 2 H) 2.77 - 2.90 (m, 4 H) 3.74 (s. 3 H) 4.69 (s, 2 H) 7.18 (d. J =7.8 Hz, 1 H) 7.48 - 7.56 (m, 2 H) 7.56 -7.64 (m, 2 H) 7.74 - 7.83 (m, 2 H) 191 ( s. 1 H) 8.71 Cs, 2 H) MS (ESI/APCI Dual): 472 CM+1X 470 (Ml) 204 3HPr-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.29 (s, 3 H) 1.32 (s, 3 H) 1.93 - 2.29 (m, 4 H) 2.47 - 2.63 (m, 2 H) 2.92 - 3.10 (m. 1 H) 3.74 (s. 3 H) 4.69 (s, 2 H) 7.39 - 7.48 (m, 2 H) 7.49 - 7.57 (m, 2 H) 7.62 - 7.72 (m, 1 H) 7.74 - 7.84 (m, 3 H) 7.94 (s, 1 H) 8.72 (s, 2 H) MS (ESI /APCI Dual): 460 (Μ+Ί), 458 (Ml) 205 3—Cl - 4-MeO—Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.99 - 2.13 Cm. 2 H) 2.13 -2.31 (mt 2 H) 2.45 - 2.64 (m, 2 H) 3.74 (s. 3 H) 3.98 (s, 3 H) 4.72 (s, 2 H) 7.03 (d. J=7.8 Hz. 1 H) 7.46 - 7.59 (m 2 H) 7.73 - 8.14 (m, 5 H) 8.74 (s. 2 H) MS (ESI/APCI Dual): 482 (M+1), 480 (M-1) RA RB 206 3-C Bu 4- Me-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.95 - 2.28 Cm, 4 H) 2.44 -2.63 (m, 5 H) 3.74 (s. 3 H) 4.70 (s. 2 H) 7.29 - 7.43 (m , 3 H) 7.69 (dd. J=7.9, 1.87 Hz, 1 H) 7.91 (d, J=1.71 Hz, 1 H) 8.01 - 8.07 (m, 1 H) 8.62 - 8.56 (m, 1 H) 8.71 ( s, 2 H) MS (ESI/APCI Dual): 484 (M+1), 482 (M-1) 〇4γ^〇, Η RA RB 207 3,5_diMe-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.05 - 1.14 (m, 2 H) 1.35 -1.47 (m, 2 H) 2.41 (s, 6 H) 3.71 (s. 3 H) 4.58 (s, 2 H) 7.21 (s. 1 H) 7.45 - 7.58 (m. 4 H) 7.73 - 7.82 (m, 2 H) 7.85 (s, 1 H) 8.71 (s, 2 H) MS ( ESI/APCI Dual): 432 (M+1). 430 (M-1) 208 CO ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.05 - 1.14 (m, 2 H) 1.37 -1.46 (mt 2 H) 1.79 - 1.89 (m, 4 H) 2.77 - 2.90 (m, 4 H) 3.70 (s, 3 H) 4.58 (s, 2 H) 7.19 (d. J=7.8 Hz, 1 H) 7.48 - 7.64 (m. 4 H) 7.72 -7.83 (m, 2 H) 7.88 (s, 1 H) 8.71 Cs, 1 H) MS (ESI/APCI Dual); 458 (M+1), 456 (M-1) 209 3'iPr- Ph ch3 1H NMR C300 MHz. CDCf3) δ ppm 1.06 - 1.13 (m, 2 H) 1.30 (s, 3 H) 1.32 (s, 3 H) 1.38 - 1.45 (m. 2 H) 3.01 (m, 1 H) 3.70 (s, 3 H) 4.57 (s, 2 H) 7.41 - 7.47 (m, 2 H) 7.50 - 7.57 (m, 2 H) 7.64 - 7.70 Cm, 1 H) 7.75 - 7.82 (m. 3 H) 7.91 (s, 1 H) 8.71 Cs, 2 H) MS (ESI/APCI Dual): 446 (M+1), 444 (M-1) 210 3~CI-4-Me〇-Ph ch3 1H NMR ¢300 MHz , CDCI3) δ ppm 1.05 - 1.16 (m, 2 H) 1.38 -1.47 (m, 2 H) 3.70 (s. 3 H) 3.99 (s, 3 H) 4.60 (s. 2 H) 7.03 (d, J=8.7 Hz, 1 H) 7.53 (d, J=8.6 Hz, 2 H) 7.72 - 7.88 (m, 4 H) 7.94 Cd. J=2.3 Hz , 1 H) 8.74 (s. 2 H) MS (ESI/APCI Dual): 468 (M+1), 466 (M-1) 〇丫0'RB RA RB 211 3-CI-4-Me-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.37 (s. 6 H) 2.46 (s, 3 H) 3.72 (s. 3 H) 4.46 (s, 2 H) 7.37 (d, J=8.1 Hz. 1 H) 7.50 - 7.58 (m, 2 H) 7.66 - 7.72 (m, 1 H) 7.73 - 7 80 (m, 2 H) 7 8Z - 7.91 (m. 2 H) 8.72 (s, 2 H) MS (ESI/APCI) Dual): 454 (M+1), 452 (M-1) -279- 200918053 [Table 20] 丫, β Η Η RA RB 212 3-CI-Ph ch3 ΊΗ NMR ¢ 300 MHz, CDCI3) 5 ppm 1.95 - 2.25 (m, 4H) 2.48- 2.65 (m, 2H) 3.74 (ε, 3H) 4.69 (s, 2H) 6.95 - 7.50 (m. 10H) 8.54 - 8.66 (m, 2H) MSCES1): 467 (M+ 1), 465(M-1) Ming F RA RB 213 2-CI-4-F-Ph ch3 1H NMR (300 MHz, DMS〇-d6) 5ppm 1.79 - 2.17 (m, 4 H) 2.33 -2.50 (m , 2 H) 3.65 (s, 3 H) 4.63 (s, 2 H) 7.18 - 7.28 (m, 1 H) 7.50 (dd. J=8.6, 2.8 Hz, 1 H) 7.54 - 7.61 (m. 1 H) 7.75 (dd, J=13.1, 1.9 Hz. 1 H) 8.11 (dd. J=9.4, 5.8 Hz, 1 H) 8.28 (t, J=8 .8 Hz, 1 H) 8.78 - 8.90 (br, 1 H) 8.95 (s, 2 H) 9.36 - 9.49 (br, 1 H) MS (ESI/APCI Dual): 503 (M+1), 501 (ΜΊ 214 2-C 卜 5-F-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.96 - 2.25 (m. 4 H) 2.48 -2.62 (m, 2 H) 3.74 (s, 3 H) 4.69 (s 2 H) 6.74 (ddd, J=8.9, 7.5, 3.0 Hz. 1 H) 7.21 (dd, J=11.8, 2.0 Hz, 1 H) 7.26 - 7.35 (m. 3 H) 7.38 -7.44 (br, 1 H) 8.13 (dd, J=11.0, 3.0 Hz. 1 H) 8.26 (t. J=8.4 Hz, 1 H) 8.65 (s, 2 H) MS (ESI/APCI Dual): 503 (M+1), 501 (M-1) 215 2-F-5 - CF3 - Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.96 - 2.26 (m, 4 H) 2.48 -2.63 (m, 2 H) 3.77 (s. 3 H) 4.70 (s, 2 H) 7.08 - 7.34 (m, 4 H) 7.39 -7.45 (m. 1 H) 7.49 - 7.57 (m. 1 H) 8.29 (t. J=8.4 Hz, 1 H) 8.60 ( s, 2 H) 8.58 - 8.66 (m, 1 H) MS (ESI/APCI Dual): 537 (M+1). 535 (M-1) 216 2-F-5-Me-Ph ch3 1H NMR (300 MHz, CDCI3) &lt;5 ppm 1.95 - 2-25 (m, 4 H) 2.32 (s, 3 H) 2.48 - 2.62 (m, 2 H) 3.75 (s. 3 H) 4.69 (s. 2 H) 6.77 - 6.86 (m 1 H) 6.95 (dd, J=10.7, 8.2 Hz, 1 H) 7.15 (dd. J=11.8, 2.0 Hz. 1 H) 7.22 - 7.30 (m, 2 H) 7 35 - 7 41 (m, 1 H) 7.89 - 7.96 (m, 1 H) 8.30 (t, J 8.5 hU· 1 H) 8 62 (s. 2 H) MS (ESI/APCI Dual): 483 (M+1). 481 (M- 1) 〇Y〇&gt;8 Hirose. 4 Η M RA RB 217 2-CI-4-F-5-Me-Ph ch3 MSCESI). 499CM+1), 497(M-1) 218 2_C Bu 4-F-Ph ch3 MS(ESI): 485( M+1), 483(M-1) 219 3-CI-4-F-Ph ch3 MS(ESl): 485(M+1), 483(M-1) 220 2-F-5-Me-Ph Ch3 MS (ESI): 465 (M+1), 463 (M-1) 221 2-F-3-C mp Ph Ch3 MS (ESI): 485 (M+1), 483 (M-1) 222 3 -CF3-4-Me-Ph ch3 MS (ESI): 515 (M+1), 513 (M-1) 223 3-CF3-4-F-Ph ch3 MS (ESI): 519 (M+1), 517CM-1) 224 3-Me〇-4-CI-Ph ch3 MS (ESI): 497 (M+1), 495 (M-1) 225 3-CI-4-MeO-Ph ch3 MS (ESI): 497CM+1), 495(M-1) 226 3-iPr - Ph gh3 MS(ESI): 475CM+1), 473(M-1) 227 2-CF3-4-F-Ph ch3 MS (ESI): 519(M+1), 517(M-1) 228 2-F-5-CF3-Ph ch3 MS(ESI): 519(M-t1), 517(M-1) 229 2-Me-5*CF3 -Ph ch3 MS (ESI): 515 (M+1), 513 (M-1) 230 2-C bis 5-F-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.98 - 2.29 (m, 4H) 2.50 -2.65 (m, 2H) 3.76 (s, 3H) 4.70 (s. 2H) 6.70 - 6.80 (m. 1H) 6.74 (s, 1H) 7.27 - 7.34 (m. 2H) 7.49 - 7.59 (m, 4H) 8.15 (dd, J=3.0 Hz, 11.0 Hz, 1H) 8.71 (sT 2H) MS (ESI): 485 (M+1). 483 (M-1) -280- 200918053 [表卜21] 丫RA RB 231 3-MeO-4-CI-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.04 - 1.15 (m, 2 H) 1.34 -1.47 (m, 2 H) 3.69 (s, 3 H) 3.86 ( s, 3 H) 4.56 (s. 2 H) 6.67 (dd. J=8.6, 2.3 Hz, 1 H) 7.06 - 7.54 (m, 6 H) 8.61 ts, 2 H) MS (ESI/APCI Dual): 483 (M+1), 481 (M-1) 232 3-CI-Ph ch3 1H NMR ¢300 MHz, CDCI3) 6 ppm 1.07 - 1.12 (m, 2 H) 1.36 -1.42 (m, 2 H) 3.69 (s , 3 H) 4.56 (s. 2 H) 6.96 (ddd, J=7.9, 1.9. 0.9 Hz, 1 H) 7.18 (t, J=8.1 Hz, 1 H) 7.37 - 7.46 (m, 3 H) 7.54 ( t, J=2.0 Hz, 1 H) 7.57 - 7.66 (m, 2 H) 8.55 (s. 1 H) 8.62 (s, 1 H) 8.64 (s, 2 H) MS (ESI/APCI Dual); 451 ( M-1) 233 3-CI-4-Me〇-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.06 - 1.12 (m, 2 H) 1.37 -1.44 (m, 2 H) 3.69 (s, 3 H ) 3.84 (s. 3 H) 4.56 (s, 2 H) 6.83 (d, J=8.7 Hz, 1 H) 7.34 - 7.43 (m. 4 H) 7.50 - 7.57 (m, 2 H) 8.04 (s, 1 H) 8.13 (s, 1 H) 8.63 (s. 2 H) MS (ESI/APCI Dual): 483 (M+1). 481 (M-1) 234 3-CI-4-F-Ph ch3 1H NMR (300 MHz, CDCI3) &lt;5 ppm 1.07 - 1.13 Cm, 2 H) 1.37 -1.46 (m. 2 H) 3.69 (s, 3 H) 4.57 (s, 2 H) 7.05 Ct. J=8.7 Hz, 1 H) 7.20 - 7.26 ( m, 1 H) 7.31 (s, 2 H) 7.35 - 7.53 (m. 5 H) 8.61 (s, 2 H) MS (ESI/APCI Dual): 471 (M+1), 469 (M-1) 235 2-F-5-Me-Ph ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.06 - 1.13 (m, 2 H) 1.39 -1.46 (m. 2 H) 2.32 (s, 3 H) 3.70 (s, 3 H) 4.56 (s, 2 H) 6.77 - 6.84 (m, t H) 6.90 - 7.04 (m, 2 H) 7.22 (s. 1 H) 7.36 - 7.43 (m, 2 H) 7.45 - 7.52 Cm, 2 H 7.90 - 7.97 (m, 1 H) 8.62 Cs, 2 H) MS (ESI/APCI Dual): 451 (M+1), 449 (Μ~1) 236 3-CF3_4-F-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.01 - 1.17 Cm, 2 H) 1.35 -1.49 (m, 2 H) 3.69 (s, 3 H) 4.57 (s, 2 H) 7.04 - 7.17 (m, 1 H) 7.34 -7.68 Cm , 7 H) 7.74 (s, 1 H) 8.60 Cs, 2 H) MS (ESI/APCI Dual): 505 (M+1). 503 (M-1) 237 2-CF3-4-F-Ph ch3 1H NMR (300 MHz. CDCI3) 6 ppm 1.03 - 1.16 (m, 2 H) 1.34 -1.46 (m. 2 H) 3.69 (s, 3 H) 4.57 (s. 2 H) 6.98 - 7.66 (m, 7 H) 8.64 (s, 2 H) MS (ESI/APCI Dual): 505 (M+1), 503 (MD 238 2-F-5-CF3-Ph ch3 1H NMR ¢300 MHz, CDCI3) β Ppm 1.05 - 1.14 (m, 2 H) 1.40 -1.48 (m. 2 Η) 3.7Ϊ (s, 3 H) 4.57 (s, 2 H) 6.91 - 7.35 (m, 4 H) 7.42 -7.56 (m, 4 H) 8.55 - 8.70 (m, 3 H) MS (ESI/APCI Dual): 505 (M+1), 503 (M-1) 0 丫. , RA RB 240 3_Me-4-F—Ph ch3 1H NMR (300 MHz, CDCI3) &lt;5 ppm VS6 - 2 22 (m, 7 H) 2.45 - 2.60 (m, 2 H) 3.73 (s, 3 H) 4.61 (s, 2 H) 6.74 (d, J=8.6 Hz, 1 H) 6.80 - 6.89 (m, 1 H) 6.94 - 7.04 (m, 1 H) 7.08 (dd, J=6.8, 2.6 Hz, 1 H) 7.24 - 7.35 (m, 5 H) 7.38 (s. 1 H) 7.61 (dd , J=8.6, 2.6 Hz, 1 H) 8.23 (dd, J=2.5, 0.6 Hz. 1 H) MS (ESI/APCI Dual): 464 (M+1). 462(M-1) 241 2-Br ~5-Me-Ph ch3 1H NMR (300 MHz, CDCI3) 6 ppm 1.88 - 2-21 (m, 4 H) 2 30 (s, 3 H) 2.45 - 2.61 (m, 2 H) 3.74 (s. 3 H) 4.62 (s. 2 H) 6.76 (dd. J=8.0, 1.6 Hz, 1 H) 6.80 (d. J=8.6 Hz, 1 H) 7.10 (d. J=4.7 Hz, 2 H) 7.37 (d , J=8.1 Hz, 1 H) 7.46 (s, 4 H) 7.74 (dd, J=8.6, 2.6 Hz, 1 H) 7.97 Cd, J=1 7 Hz, 1 H) 8 33 Cd. J=1.9 Hz , 1 H) 242 2-CI-4-F-5-Me-Ph ch3 1H NMR ¢300 MHz, CDCI3) (5 ppm 1.91 - 2.21 (m, 4 H) 2.24 (d, J=2.0 Hz. 3 H ) 2.44 - 2.61 (m. 2 H) 3.74 (s. 3 H) 4.62 (s. 2 H) 6.80 (d. J=8.7 Hz, 1 H) 6.98 (d. J=4.4 Hz, 2 H) 7.04 ( d, J=8.9 Hz, 1 H) 7.40 - 7.51 (m, 4 H) 7.74 (dd, J=8.6, 2.6 Hz, 1 H) 7.97 (d, J=7.5 Hr. 1 H) 8.32 (d, J =2.0 Hz. 1 H) MS (ESI/APCI Dual): 498 (M+1), 496CM- 1) -281 - 200918053 [表卜22] 243 3-CF3-Ph ch3 1H NMR (300 MHz. CDC13) 6ppm 1.89 - 2.23 (m, 4 H) 2.40 -2.62 (m, 2 H) 3.75 (s. 3 H) 4.63 (s, 2 H) 6.77 (d, J=8.6 Hz, 1 H) 6.95 (s, 1 H) 7.13 (s, 1 H) 7.28 - 7.34 (m, 1 H) 7.34 - 7.47 (m, 5 H) 7.60 (d, J=7.9 Hz, 1 H) 7.63 - 7.78 (m, 2 H) 8.28 (d, J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 500 (M+1) , 498CM-1) 244 3-CF3-4-CI-Ph ch3 1H NMR (300 MHz, CDCI3) &lt;5 ppm 1.92 - 2.23 Cm, 4 H) 2.47-2.61 (m, 2 H) 3.77 (s. 3 H) 4.64 (s, 2 H) 6.75 (d, J=8.6 Hz, 1 H) 7.08 (s 1 H) 7.29 - 7.42 (m, 6 H) 7.56 - 7.61 (m. 1 H) 7.62 ~ 7.71 Cm, 2 H) 8.24 (d, J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 534 (M+1), 532CM-1) 245 2 - F-5-Me-Ph ch3 1H NMR ¢300 MHz, CDCI3) (5 ppm 1.92 - 2.23 (m, 4 H) 2.33 (s, 3 H) 2.45 - 2.62 (m, 2 H) 3.74 (s, 3 H) 4.63 (s, 2 H) 6.78 - 6.91 (m, 4 H) 6.96 (dd, J=10.8. 8.3 Nz. 1 H) 7.46 (s, 4 H) 7.76 (dd, J=8.7, 2.5 Hz, 1 H) 7.92 Cdd, J=7.2, 1.6 Hz, 1 H) 8.33 (d, J=2.5 Hz, 1 H) MS (ESI/APCI Dual): 464 (M+1), 462CM-1) 246 2-CF3-4-CI-Ph ch3 MSCESI): 534CM+1), 532CM-1) 247 3 - Me-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.96 - 2.21 (m, 4 H) 2.29 (s, 3 H) 2.46 - 2.61 (m, 2 H) 3.74 (s, 3 H) 4.62 (s, 2 H) 6.77 (d, J=8.6 Hz, 1 H 6.91 (d, J=7.5 Hz, 1 H) 7.04 (s, 1 H) 7.08 - 7.23 (m, 4 H) 7.34 - 7.44 (m, 4 H) 7.67 (dd, J=8.6, 2.5 Hz, 1 H) 8.22 - 8.34 (m. 1 H) MS (ESI/APCI Dual): 446 (M+1), 444CM-1) 248 3-CF3〇-Ph ch3 1H NMR (300 MHz, CDCI3) 6 Ppm 1.92 - 2.21 (m, 4 H) 2.47 - 2.60 (m. 2 H) 3.75 (s. 3 H) 4.63 (st 2 H) 6.77 (d, J=8.6 Hz. 1 H) 6.88 - 6.99 (m, 2 H) 7.04 - 7.14 (m. 1 H) 7.28 - 7.33 (m, 1 H) 7.34 - 7.49 (m, 5 H) 7.66 - 7.74 (m, 1 H) 8.29 Cs, 1 H) MS (ESI/APCI Dual): 516 (M+l), 514 (M-1) 249 2-CI-4-CF30-Ph ch3 1H NMR ¢300 MHz, DMSO-D6) 5ppm 1.79 - 2.13 Cm. 4H) 2.30 -2.45 (m , 2H) 3.63 (s, 3H) 4.56 (s, 2H) 6.85 (d. J=8.7 Hz, 1H) 7.38 (d, J=9.3 Hz, 1H) 7.55 (d. J=9.0 Hz, 2H) 7.57 - 7.64 (m, 3H) 7.97 (dd, J=2.6 Hz, 8.9 Hz, 1H) 8.28 (d, J=9.0 Hz, 1H) 8.43 (d. J=2.4 Hz. 1H) 8.45 - 8.47 (br. 1H) 9.54 - 9.57 (br. 1H) MSCESI): 550CM+1), 548(M-1) 250 2-Me-4-CF30-Ph ch3 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.80 - 2.14 (m (4.) (3. 7.23 (s, 1H) 7.56 (d. J=9.0 Hz, 2H) 7.61 (d. J=8.7 Hz. 2H) 7.98 (dd, J=2.0 Hz, 8.9 Hz. 2H) 8.08 (s. 1H) 8 44 fd. J=? 4 H7. 1H) 9 ?Π U, 1M) MS(ESI): 530 (M+1) 528 (M-1) 251 2_F-5-CF3-Ph ch3 MSCESI): 518 (M+1), 516(M-1) 252 3-CI-Ph ch3 1H NMR (300 MHz, CDCI3) &lt;5 ppm 1.92 - 2.20 Cm. 4H) 2.45 - 2.60 (m, 2H) 3.75 (st 3H) 4.62 (s, 2H) 6.75 (d, J=8.6 Hz, 1H) 7.01 (d, J=7.4 Hz, 1H) 7.06 - 7.25 (m. 4H) 7.30 - 7.42 (m, 3H) 7.34 (d. J=8.6 Hz. 2H) 7.63 - 7.68 (m, 1H) 8.26 (d, J=2-4 Hz, 1H) MSCESI): 466(M+1), 464(M-1) 253 3,5-diCI-Ph ch3 1H NMR ¢300 MHz, DMSO-D6) 5 ppm 1.80 - 2.13 (m, 4H) 2.23 -2.45 (m , (2,3H) 8.41 - 8.45 Cm. 1H) 8.98 - 9.04 (br, 1H) 9.06 - 9.12 (br, 1H) MSCESI): 500(M+1). 498(M-1) 254 3-C Bu 4-MeO-Ph ch3 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.82 * 2.45 (m, 6H) 3.63 (s, 3H) 3.80 (s, 3H) 4.55 (s, 2H) 6.85 (d, J=8.3 Hz, 1H) 7.08 (d, J=8.9 Hz, 1H) 7.27 (d, J=8.6 Hz, 1H) 7.53 (d, J=8.3 Hz, 2H) 7.58 (d, J=8.6 Hz, 2H) 7.64 - 7.67 (m, 1H) 7.96 (d, J=8.6 Hz, 1H) 8.43 (s, 1H) 8.67 (s. 1H) 8.79 (s, 1H) MSCESI): 496(M+1). 494(M-1) 255 2- Me-4-CN-Ph ch3 MS (ESI): 47HM+1), 469 (M-1) 256 2-F-3-CI-Ph ch3 MS (ESI): 484 (M+1) 482CM-1) 257 4 a t A Bu-Ph ch3 1H NMR ¢ 300 MHz. DMSO-D6) 6 ppm 1.27 (s. 9H) 1.80 - 2.15 Cm, 4H) 2.25 - 2.60 (m. 2H) 3.64 (s, 3H) 4.57 (s, 2H) 6.86 (d, J=8.4 Hz, 1H) 7.30 (d, J=9.0 Hz. 2H) 7.38 (d, J=8.7 Hz. 2H) 7.54 (d, J=8.7 Hz, 2H) 7.59 (d, J= 8.7 Hz, 2H) 7.97 (dd, J=2.3 Hz, 8.6 Hz, 1H) 8.41 (d, J=2.7 Hz, 1H) 8.61 (s, 1H) 8.74 (s, 1H) MS(ESI): 488 (M +1) 486 (M-1) 258 2-Me-5-CF3-Ph ch3 MSCESI): 514CM+1), 512(M-1) 259 3-iPr-Ph ch3 MSCESI): 474 (M+1) 472 (M-1) -282- 200918053 [Table 1-23] 260 3-MeO-4-CI-Ph ch3 1H NMR (300 MHz, DMSO-D6) δ ppm 1.80-2.14 (m, 4H) 2.32 -2.47 (m, 2H) 3.64 (s, 3H) 3.83 (s, 3H) 4.56 (s, 2H) 6.86 (d, J=8.6 Hz, 1H) 6.96 (dd, J=2.4 Hz. 8.6 Hz, 1H) 7.29 ( d, J=8.6 Hz, 1H) 7.42 (d. J=2.1 Hz. 1H) 7.54 (d. J=8.9 Hz, 2H) 7.59 (d, J=9.2 Hz, 2H) 7.96 (dd, J=2.4 Hz , 8.6 Hz, 1H) 8.43 (d, J=2.7 Hz, 1H) 8.82 (s, 1H) 8.87 (s, 1H) MS(ESI): 496 (M+1) 494 (M-1) 261 χ:: Ch ch3 1H NMR (300 MHz, DMSO-D6) 5ppm 1.80 - 2.20 Cm. 4H) 2.30 -2.50 (m, 2H) 3.66 (s. 3H) 4.58 (s, 2H) 6.88 (d, J=8.6 H z, 1H) 7.12 (dd. J=2.1 Hz, 8.6 Hz, 1H) 7.34 (d, J=8.9 Hz, 1H) 7.55 (d, J=8.9 Hz, 2H) 7.61 (d, J=8.6 Hz. 2H 7.69 (d, J=1.8 Hz. 1H) 7.98 (dd, J=2.4 Hz, 8.6 Hz, 1H) 8.45 (d, 2.4 Hz, 1H) 8.87 (s, 1H) 8.95 (s, 1H) MS (ESI ): 512(M+1), 510CM-1) 262 3-CF3-4-Me-Ph ch3 1H NMR ¢300 MHz, CDCI3) «5ppm 1.90 - 2.20 Cm, 4H) 2.36 (s. 3H) 2.45 - 2.60 (m. 2H) 3.75 (s, 3H) 4.62 (s, 2H) 6.74 (d. J=8.4 Hz, 1H) 7.13 (d. J=7.8 Hz, 1H) 7.25 - 7.49 (m. 8H) 7.61 (dd , J=2.6 Hz, 8.6 Hz, 1H) 8.23 (d, J=2.4 Hz, 1H) MS(ESI): 514(M+1), 512CM-1) 263 2-G Bu 5-CF3-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.90 - 2.21 Cm, 4H) 2.46 - 2.62 (m, 2H) 3.76 (s, 3H) 4.63 (s, 2H) 6.77 (d, J=8.4 Hz, 1H) 7.22 (d , J=8.4 Hz. 1H) 7.37 - 7.55 (m. 7H) 7.71 (dd, J=2.6 Hz. 8.6 Hz. 1H) 8.29 (d, J=2.4 Hz, 1H) 8.64 (s, 1H) MSCESI): 534(M+1), 532CM-1) 264 3-CF3-4-CN-Ph ch3 MS(ESI): 525 (M+1) 523 (M-1) 265 2-Ci-4-F-Ph ch3 1H NMR ¢300 MHz, CDCI3) (5 ppm 1.90 - 2.20 Cm, 4H) 2.46 - 2.60 (m. 2H) 3.74 (s, 3H) 4.62 (s, 2H) 6.73 - 6.83 (m, 1H) 6.80 ( d, J=8.6 Hz, 1H) 6.95 - 7.05 (m, 2H) 7.12 (dd, J=2.9 Hz, 8.3 Hz, 1H) 7.44 (d, J=8.7 Hz. 2H) 7.49 (d, J=9.0 Hz 2H) 7.75 (dd, J=2.7 Hz, 8.7 Hz, 1H) 8.13 Cdd, J=5.6 Hz, 9.2 Hz. 1H) 8.33 (d, J=2.4 Hz, 1H) MS(ESI): 484 (M+ 1), 482(M-1) 〇MH Γ RA RB 266 2-C 卜 4-F-Ph ch3 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.81 - 2.14 (m. 4H) 2.32 -2.47 ( m, 2H) 3.64 (s, 3H) 4.57 (s, 2H) 6.87 (d, J=8.7 Hz, 1H) 7.22 (td. J=2.9 Hz. 8.7 Hz. 1H) 7.49 (dd, J=2.7 Hz, 8 7 Hz, 2H) 7.63 (d, J=U.0Hz. Sichuan) 8.02 (dd, J=2.7 Hi, 8.7 Hz. 1H) 8.11 (dd, J—6.1 Hz, 9.5 Hz, 1H) 8.23 (t. J=8.6 Hz. 1H) 8.49 (d, J=3.0 Hz. 1H) 8.80 (s, 1H) 9.36 (s. 1H) MSCESI): 502(M+1), 500{M-1) °γ%Β 1 f^Y ^T] 〇Η H RA RB 267 2-CI-4-F-Ph ch3 1H NMR (300 MHz, CDCI3) (5 ppm 1.91 - 2.22 Cm. 4H) 2.44 -2.62 (m. 2H) 3.74 (s. 3H) 4.62 (s, 2H) 6.78 - 6.85 (m, 2H) 6.92 (s. 1H) 6.99 - 7.08 (m, 1H) 7.12 - 7.18 (m. 2H) 7.33 (t, J=8.5 Hz, 1H) 7.39 - 7.47 (m. 1H) 7.72 - 7.78 (m, 1H) 8.12 (dd, J=5.7 Hz, 9.2 Hz, 1H) 8.30 (s. 1H) MS (ESI ): 502CM+1) 500(M-1) 〇γ%Β Η M RA RB 268 2-CI-4-F-Ph ch3 MS(ESI): 518CM+1) 516(M-1) r,pn Η H RA RB 269 2-CI-4-F-Ph ch3 1H NMR ¢300 MHz, CDGI3) 5 ppm 1.90 - 2.20 (m, 4H) 2.25 (s, 3H) 2.47 - 2.62 (m, 2H) 3.74 (s, 3H) 4.62 (s, 2H) 6.79 (d, J=8.3 Hz, 1H) 6.85 (s, 1H) 6.96 - 7.18 (m, 4H) 7.19 - 7.28 (m, 1H) 7.30 -7.36 (m, 1H) 7.51 (dd, J=2.4 Hz, 8.3 Hz, 1H) 8.07 (d, J=2.4 Hz, 1H) 8.14 (dd, J=5.4 Hz, 9.2 Hz, 1H) MS (ESI): 498 (M+1), 496(M-1) -283- 200918053 [Table 1-24] RA RB 270 2-F-5-C 卜 Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.90 - 2.20 (m, 4H) 2.45 -2.65 (m, 2H) 3.76 (s. 3H) 4.63 (s, 2H) 6.78 (d, J=8.7 Hz, 1H) 6.90 -7.15 (m, 4H) 7.43 (s, 4H) 7.72 (dd. J=2.4 Hz , 8.7 Hz, 1H) 8.25 -8.35 (m. 2H) MSCESI): 484CM+1), 482CM-1) 271 2-C!-5-F-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.90 - 2.20 (m, 4H) 2.45 -2.65 (m, 2H) 3.75 (s, 3H) 4.63 (s, 2H) 6.68 - 6.75 (m, 1H) 6.81 (d, J=8.4 Hz, 1H) 6.96 (s, 1H) 7.25 - 7.35 (m, 2H) 7.45 - 7.55 (m, 4H) 7.76 (dd, J=3.0 Hz. 8.7 H z, IH) 8.15 (dd, J=3.0 Hz, 11.0 Hz, 1H) 8.33 (d, J=2.7 Hz, 1H) MS (ESI): 484CM+1), 482 (M-1).丫, rr&quot;^u F RA RB 272 2-C!-5-F-Ph ch3 1H NMR ¢300 MHz, CDCI3) 6 ppm 1.90 - 2.20 (m, 4H) 2.45 -2.60 (m, 2H) 3.75 (s , 3H) 4.62 (s, 2H) 6.73 (ddd, J=2.9 Hz, 7.3 Hz, 8.9 Hz. IH) 6.80 (d, J=8.4 Hz, 1H) 7.14 (d, J=2.7 Hz, IH) 7.18 - 7.38 (m, 4H) 7.73 (dd, J=2.7 Hz, 8.7 Hz. IH) 8.08 - 8.19 (m, 2H) 8.31 (d, J=2.7 Hz 1H) MS(ESI): 502 (M+1), 500 (M-1) 273 2-F-5-CF3-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.92 - 2.21 (m, 4H) 2.46 -2.61 (m, 2H) 3.76 (s. 3H) 4.62 (s, 2H) 6.77 (d, J=8.7 Hz, 1H) 7.10 -7.34 (m. 5H) 7.37 (d, J=3.3 Hz, 1H) 7.79 (dd, J=2.7 Hz. 8.7 Hz, 1H) 8.18 (dd, J=8.1 Hz. 8.4 Hz, 1H) 8.28 (d, J=2.4 Hz 1H) 8.62 (dd, J=1.8 Hz. 7.5 Hz, ΊΗ) MS(ESl): 536 (M+1), 534 (M-1) 274 2-F-5-Me-Ph ch3 1H NMR (300 MHz, CDCI3) 5 ppm 1.90 - 2.19 (m, 4H) 2.33 (s. 3H) 2.46 - 2.59 (m. 2H) 3.74 ( s, 3H) 4.62 (s. 2H) 6.79 (d, J=8.6 Hz, 1H) 6.78 - 6.86 (m, 1H) 6.88 - 7.01 (m, 3H) 7.21 (dd, J=1.9 Hz, 12.1 Hz. 1H 7.24 - 7.31 (m, 1H) 7.71 (dd, J=2.8 Hz, 8.5 Hz. 1H) 7.87 - 7.94 (m. IH) 8.19 (t, J=8 5 Hz. 1H) 8.30 (d. J=?.1 Hz 1H) MS(ESI): 482 (M+1), 480 (M-1) °^°&gt;B f fY°^J Η H RA RB 275 2-C Bu 5-F-Ph ch3 MS (ESI): 502 (M 10 1), 500 (M-1) 276 2-F-5-CF3-Ph ch3 IH NMR (300 MHz, CDCI3 6 ppm 1.92 - 2.22 (m, 4H) 2.48 -2.61 (m, 2H) 3.76 (s, 3H) 4.63 (s, 2H) 6.78 (d. J=8.9 Hz, 1H) 7.09 (dd, J=1.9 Hz) , 8.5 Hz, IH) 7.13 - 7.34 (m, 5H) 7.43 (dd. J=2.2 Hz, 12.4 Hz, IH) 7.71 (td. J=2.1 Hz, 8.9 Hz, 1H) 8.25 (s. 1H) 8.61 ( Dd, J=1.8 Hz. 7.1 Hz. 1H) MS(ESI): 536 (M+1), 534 (M-1) °Y°&gt;B 〇RA RB 277 2-C Bu 5-F-Ph ch3 MS (ESI): 518 (M+1). 516 (M-1) 278 2-F-5-CF3-Ph ch3 MSCESI): 552 (M+1), 550 (M-1) -284- 200918053 Table 1-25] °丫0'RB Μ Μ RA RB 279 2-CF3-4-F-Ph Et 1H NMR ¢300 MHz, DMSO-D6) dppm 1.06 - 1.14 Cm, 2H) 1.14 (t, J=7.1 Hz, 3H) 1.20 - 1.29 (m. 2H) 4.08 (q, J=7.3 Hz, 2H) 4.43 (s, 2H) 6.90 (d, J=8.6 Hz, 1H) 7.55 (d, J=8.3 Hz, 2H 7.50 - 7.65 (m, 2H) 7.62 (d, J=8.6 Hz, 2H) 7.92 (dd. J=5.1 Hz, 9.2 Hz, 1H) 7.98 (dd, J=2.7 Hz. 8 6 Hz, 1H) 8.14 (s, 1H) 8.43 (d, J=2.7 Hz. 1H) 9.40 (s, 1H) MSCES1): 518CM+1), 516(M-1) 280 2-CF3-4-C Ph Et 1H NMR (300 MHz. DMSO-D6) 6 ppm 1.07 - 1.13 (m, 2H) 1.14 (t, J=7.1 Hz, 3H) 1.21 - 1.28 (m, 2H) 4.08 (q, J=6.9 Hz, 2H) 4.43 ( s, 2H) 6.90 (d, J=8.0 Hz, 1H) 7.56 (d, J=8.6 Hz, 2H) 7.62 (d. J=8.6 Hz, 2H) 7.70 ^ 7.78 (m. 2H) 7.99 (dd. J =2.7 Hz. 8.6 Hz. 1H) 8.04 (d, J=8.9 Hz, 1H) 8.20 (s, 1H) 8.44 (s, 1H) 9.53 (s. 1H) MS(ESI): 534(M+1), 532(M-1) 281 2-Cl-4 - CF3-Ph Et 1H NMR (300 MHz. DMSO-D6) 5ppm 1.07 - 1.15 Cm, 2H) 1.15 (t, J=7.1 Hz, 3H) 1.22 - 1.28 ( m, 2H) 4.08 (q, J=7.1 Hz, 2H) 4.44 (s, 2H) 6.91 (d, J=8.6 Hz. 1H) 7.58 (d, J=8.9 Hz, 2H) 7.64 (d. J=8.6 Hz. 2H) 7.67 - 7.75 (m, 1H) 7.87 - 7.92 (m, 1H) 7.95 - 8.03 (m, 1H) 8.42 - 8.46 (m, 1H) 8.50 (d, J=8.9 Hz, 1H) 8.67 (s , 1H) 9.73 (s, 1H) MS (ESI): 534CM+1), 532 (M-1) 282 3-CF3-4-F-Ph Et 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.07 - 1.16 (m, 2H) 1.14 (t, J=7.1 Hz, 3H) 1.21 - 1.28 (m, 2H) 4.08 (q, J=7.0 Hz, 2H) 4.43 (s, 2H) 6.90 (d, J= 8.3 Hz, 1H 7.40 - 7.51 (m, 1H) 7.56 (d, J=8.9 Hz, 2H) 7.61 (d. J=9.2 Hz. 2H) 7.60 - 7.70 (m, 1H) 7.94 - 8.05 (m. 2H) 8.43 (d , J=2.7 Hz, 1H) 8.94 Cs. 1H) 9.08 (s, 1H) MSCES1): 518CM+1), 516(M-1) 283 2-CF30-Ph Et 1H NMR (300 MHz, DMSO-D6) δ ppm 0.90 - 1.34 Cm, 7H) 4.07 (q, J=7.0 Hz. 2H) 4.43 (s, 2H) 6.89 (d. J=8.6 Hz, 1H) 7.10 (dd. J=7.4 Hz. 7.4 Hz, 1H 7.20 - 7.45 (m, 2H) 7.57 (d, J=8.3 Hz. 2H) 7.62 (d, J=8.3 Hz, 2H) 7.97 (d, J=8.6 Hz, 1H) 8.29 (d. J=8.6 Hz) , 1H) 8.43 (s. 1H) 8.15 Cs, 1H) 9.40 (s, 1H) MS (ESI): 516 (_) 514 (M-1) 284 3-CI-4-F-Ph Et 1H NMR (300 MHz. DMSO-D6) 6 ppm 1.00 - 1.30 Cm. 7H) 4.07 (q, J=6.9 Hz. 2H&gt; 4.42 (s, 2H) 6.89 (d, J=8.9 Hz, 1H) 7.26 - 7.39 (m, 2H 7.53 (d, J=8.6 Hz, 2H) 7.59 (d, J=9.2 Hz, 2H) 7.81 (d. J=6.8 Hz. 1H) 7.96 (dd. J= 2.7 Hz. 8.9 Hz, 1H) 8.41 ( d. J=2.1 Hz, 1H) 8.88 (s, 1H) 8.91 (s, 1H) MS (ESI): 484 (M+1) 482 (M-1) 285 2-CI-4-CF30-Ph Et 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.02 - 1.27 (m, 4H) 1.13 (t, J = 7.0 Hz, 3H) 4.07 (q, J = 7.1 Hz, 2H) 4.42 (s. 2H) 6.89 (d, J=8.6 Hz, 1H) 7.32 - 7.43 (m, 1H) 7.47 Cm, 1H) 7.55 (d, J=8.6 Hz. 2H) 7.61 (d, J=8.6 Hz. 2H) 7.97 (dd, J =2.7 Hz, 8.6 Hz, 1H) 8.28 (d, J=9.2 Hz, tH) 8.42 (d, J=2.4 Hz. 1H) 8.48 (s, 1H) 9.56 Cs. 1H) MS(ESI): 550CM+1 ), 548(M-1) 286 2-Me-4-CF3〇-Ph Et 1H NMR (300 MHz, CDCI3) δ ppm 1.05 (q, J=3.8 Hz, 2H) 1.22 (t, J=6.9 Hz, 3H) 1.38 (q. J=3.8 Hz, 2H) 2.29 (s, 3H) 4.16 (q, J=7.1 Hz. 2H) 4.50 (s. 2H) 6.34 (s, 1H) 6.62 (s, 1H) 6.82 ( d, J=8.7 Hz, 1H) 7.06 - 7.16 (m, 2H) 7.43 (d, J=8.9 Hz, 2H) 7.48 (d, J=8.9 Hz, 2H) 7.63 (d. J=9.5 Hz. 1H) 7.74 (dd. J=2.7 Hz. 8.6 Hz. 1H) 8.30 (d, J=2.1 Hz. 1H) MS(ESI): 530(M+1), 528(M-1) 287 3-CF30-Ph Et 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.07 - 1.26 (m, 4H) 1.13 (t. J = 7.1 Hz, 3H) 4.07 (q, J = 7.2 Hz, 2H) 4.42 (s. 2H) 6.89 (d, J=8.3 Hz, 1H) 6.95 (d, J=7.7 Hz, 1H) 7.30 (d. J=8.9 Hz, 1H) 7.40 (t. J=8.3 Hz, 1H) 7.54 (d. J=8.6 Hz. 2H) 7.60 (d, J=8.9 Ηζτ 2H) 7.70 (s, 1H) 7.97 (dd, J=2.5 Hz. 8.5 Hz, 1H) 8.42 (d, J=2.4 Hz, 1H) 8.89 fSi 1H) 9 04(s, 1H) MS(ESI): 516 (M+1) 288 cycloHexyl Et 1H NMR (300 MHz, DMSO-D6) δ ppm 1.04 - 1.39 (m, 12H) 1.48 - 1.60 (m. 1H) 1.60 - 1.73 (m, 2H) 1.76 - 1.86 (m, 2H) 3.37 -3.55 (m, 1H) 4.07 (q, J=7.0 Hz. 2H) 4.41 (s, 2H) 6.10 (d, J=8.1 Hz, 1H) 6.87 (d, J=8.7 Hz, 1H) 7.45 (d, J=8.7 Hz, 2H) 7.52 (d, J=8.7 Hz, 2H) 7.94 (dd. J=2.6 Hz, 8.6 Hz, 1H) 8.39 (d, J=2.4 Hz. 1H) 8.41 (s, 1H) MS (ESI): 438 (M+l) 436 (M-1) 289 2-F-5-CF3-Ph ch3 MS (ESI): 504 (M+1), 502 (M-1) cu /T. Seven RA RB 290 2-C Bu 4-F-Ph ch3 1H NMR ¢300 MHz, CDCI3) δ ppm 1.65 - 1.86 Cm, 6H) 2.10 -2.24 (m, 2H) 3.72 (s, 3H) 4.43 (s, 2H 6.80 (d, J=8.6 Hz, 1H) 6.85 (s, 1H) 6.97 - 7.07 (τη, 2H) 7 13 (dd, J=3.0 Hz, 8.0 Hz, 1H) 7.42 -7.53 (m, 4H) 7.75 (dd. J=2.7 Hz, 8.6 Hz, 1H) 8.14 (dd, J=5.4 Hz, 9.2 Hz, 1H) 8.33 (d, J-2A Hz, 1H) MS(ESI): 498 (M-^0 496 (M-1) -285- 200918053 [Table 1 - 2 6] 291 2-F-5-Me - Ph ch3 1H NMR (300 MHz, CDCI3) ¢5 ppm 1.64- 1.84 (m, 6H) 2.06-2.24 ( m, 2H) 2.31 (s, 3H) 3.72 (s, 3H) 4.42 (s, 2H) 6.77 (d, J=8.6 Hz, 1H) 6.77 - 6.83 (m. 1H) 6.87 - 6.99 (m, 3H) 7.40 - 7.45 (m, 4H) 7.72 (dd, J=2.5 Hz, 8.2 Hz, 1H) 7.92 (d, J=8.6 Ηζ·1H) 8.29 (d. J=2.4Hz, 1H) MS(ESI): 478 ( M+1) 476 (Ml) 0 ΗH RA RB 292 2,4-diMe-Ph Et 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.10 (t J=7.2 Hz, 3H) 1.21 -1.64 ( m. 8H) 1.96-2.10 (m. 2H) 2.20 (s. 3H) 2.22 (s, 3H) 4.07 (qr J=7.1 Hz, 2H) 4.32 (s, 2H) 6.81 (dt J=8.3 Hz, 1H) 6.95 (d, J=8.3 Ηζ·1H) 6.98 (s. 1H) 7.52 (d. J=9.0 Hz, 2H) 7.57 (d, J=9.0 Hz, 2H) 7.65 (d, J=7.8 Hz. 1H) 7.86 (s, 1H) 7.95 (dd, J=2.7 Hz, 8.6 Hz, 1H) 8.40 (d. J= 2.7 Hz. 1H) 9.04 (s, 1H) MSCESI): 502 (M+1) 293 2-CI-4-F-Ph Et 1H NMR ¢ 300 MHz, DMSO-D6) 5 ppm 1.10 (t J = 7.2 Hz, 3H) 1.20 -1.64 (m. 8H) 1.98 - 2.09 (m. 2H) 4.07 (q, J=7.3 Hz. 2H) 4.32 (s, 2H) 6.81 (d, J=8.7 Hz, 1H) 7.21 (td, J=2.8 Hz, 8.7 Hz, 1H) 7.4S (dd, J=3.0 Hz. 8.7 Hz. 1H) 7.53 (d, J=9.0 Hz. 2H) 7.59 (d, J=8.7 Hz, 2H) 7.95 (dd J=2.5 Hz. 8.5 Hz. 1H) 8.11 (dd, J=5.8 Hz, 9.4 Hz, 1H) 8.32 (s, 1H) 8.40 (d. J=2.1 Hz, 1H) 9.44 (s, 1H) MStESi) : 526(M-*-l), 524(M-1) °V0&quot;® 〇Η H RA RB 294 3-CF30-Ph ch3 1H NMR (300 MHz, CDC13) δ ppm 1.96 - 2.25 Cm. 4 H) 2.49 -2.61 (m, 2 H) 3.75 (s, 3 H) 4.69 (s, 2 H) 6.90 - 6.99 (m. 2 H) 7.01 -7.09 (m, 1 H) 7.28 - 7.36 (m, 2 H) 7.37 - 7.49 (m, 5 H) 8.63 (s, 2 H) MS (ESI/APCI Dual): 517 CM+1), 515 CM-1) 丫'«Β ,丫4 RA RB 295 3-CF30-Ph Et 1H NMR ¢300 MHz. CDCI3) &lt;5 ppm 1.10 (q. J=3.8 H2, 2H) 1.22 (t, J=7.2 Hz. 3H) 1.43 (q, J=3.9 Hz, 2H) 4.15 (q, J=7.0 Hz, 2H) 4.57 ( s. 2H) 6.90 - 6.96 (m, 1H) 7.12 (s, 1H) 7.19 (s. 1H) 7.27 - 7.35 Cm, 2H) 7.35 - 7.43 (m, 3H) 7.44 (d. J=8.7 Hz. 2H) 8.59 (s, 2H) MS (ESI): 517CM+1), 515 (M-1) 296 2-Me-4-CF3 〇-Ph Et 1H NMR (300 MHz, CDCI3) (5 ppm 1.08 (q, J =3.9 Hz, 2H) 1.21 (t, J=7.1 Hz. 3H) 1.40 (q, J=3.9 Hz. 2H) 2.31 (s. 3H) 4.14 (q. J=7.1 Hz, 2H) 4.57 (s. 2H 6.32 (s, 1H) 6.68 (s, 1H) 7.08 - 7.15 (m, 2H) 7.45 (d. J=8.9 Hz. 2H) 7.50 (d, J=8.9 Hz. 2H) 7.62 (d. J=9.5 Hz, 1H) 8.66 (s. 2H) MS (ESI): 531CM+1), 529CM-1) 297 2-CI-4-CF30-Ph Et 1H NMR ¢300 MHz, CDCI3) &lt;5 ppm 1.06 - M2 (m, 2H) 1.22 (t, J = 7.1 Hz, 3H) 1.38 - 1.45 (m, 2H) 4.16 (q, J = 7.2 Hz, 2H) 4.57 (s, 2H) 7.14 - 7.32 (m. 3H) 7.40 - 7.54 (m. 5H) 8.30 Cd, J=9 2 Hz, 1H) 8.64 Cs, 2H) MS (ESI): 551CM+1) 298 2-CF30-Ph Et 1H NMR (300 MHz , CDCI3) δ ppm 1.09 (q, J=3.8 Hz. 2H) 1.22 (t. J=7.2 Hz, 3H) 1.41 (q, J=3,8 Hz, 2H) 4.15 (q, J=7.1 Hz, 2H 4.58 (s, 2H) 7.01 - 7.11 (m, 3H) 7.22 - 7.34 (m. 2H) 7.47 (d, J=8.6 Hz, 2H) 7.52 (d. J=8.9 Hz. 2H) 8.27 (dd, J = 8.1 Hz, 1.5 Hz. 1H) 8.66 Cs, 2H) MS (ESI): 517 (M+1), 515CM-1) 299 2-CI_4-F-Ph Et 1H NMR (300 MHz, CDC!3) 6 Ppm 1.09 (q, J=3.9 Hz, 2H) 1.22 (t J=7.1 Hz, 3H) 1.42 (q, J=3.9 Hz. 2H) 4.15 (q. J=7.1 Hz, 2H) 4.57 (s. 2H) 6.96 - 7.10 (m, 3H) 7.13 (dd, J=2.8 Hz, 8.2 Hz, 1H) 7.44 (d, J=8.9 Hz, 2H) 7.50 (d, J=8.9 Hz. 2H) 8.13 (dd, J- ^5.5 Hz. 9.1 Hz. 1H) 8.64 (Si 2H) MS (ESI): 485CM+1). 483(M-1) -286- 200918053 [Table 1-27] Η Η RA RB 300 2-CI - 4 -F - Ph ch3 1H NMR ¢300 MHz, CDCI3) 6 ppm 1.60 - 1.88 (m, 6H) 2.07 -2.26 (m, 2H) 3.71 (s, 3H) 4 .49 (s, 2H) 6.94 - 7.04 (m, 1H) 7.10 (dd, J=2.8 Hz, 7.9 Hz, 1H) 7.17 (s, 1H) 7.33 - 7.54 (m, 5H) 8.12 (dd. J=5.7 Hz, 8.9 Hz, 1H) 8.62 (s, 2H) MS(ESI): 499 (M+1) 497 (M-1) 301 2-F-5-Me-Ph ch3 1H MMR t3〇〇MHz, CDCI3) 6 ppm 1.68 - 1.88 (m, 6H) 2.12 -2.26 (m, 2H) 2.31 (s, 3H) 3.72 (st 3H) 4.49 (s. 2H) 6.76 - 6.84 (m. 1H) 6.94 (dd, J=8.5 Hz, 10.9 Hz, 1H) .7.03 (s, 1H) 7.21 (s, 1H) 7.38 (d. J=8.6 Hz, 2H) 7.47 (d. J=8.6 Hz, 2H) 7.93 (dd, J=1.6 Hz , 7.9 Hz, 1H) 8.61 (s, 2H) MS (ESI): 479 (M+1) 477 (M-1) 〇丫%B \3 Η H RA RB 302 2,5-diCI-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.90 - 2.25 (m. 4H) 2.45 - 2.60 (m, 2H) 3.75 (s, 3H) 4.63 (s, 2H) 6.79 (d, J=8.6 Hz, 1H) 6.90 -7.00 (m. 1H) 7.17 (s, 1H) 7.23 (s, 1H), 7.25 - 7.35 (m. 1H) 7.45 (s, 4H) 7.65 - 7.80 (m, 1H) 8.31 (s. 1H) 8.36 (d, J=2.6 Hz, 1H) MSCESI): 500 (M+1) 498 (M-1) 0 丫, ,^r°^ 0 Η H RA RB 303 4-CF30-Ph Et 1H NMR ¢300 MHz, DMSO- D6) δ ppm 1.00 - 1.29 (m, 7H) 4.07 (q. J=7.1 Hz. 2H) 4.42 (s, 2H) 6.89 (d, J=8 .9 Hz, 1H) 7.29 (d, J=BO Hz, 2H) 7 46 - 7 68 (m, 6H) 7.97 (d, J=8.6 Hz, 1H) 8.42 (s, 1H) 3.85 (3⁄4. 1H) 8.32 (s, 1H) MS (ESI): 516 (M+1) 514 (M-1) 〇丫%B RA RB 239 4 - CF3〇-Ph Et ΊΗ NMR (300 MHz, CDCI3) t5ppm 1.05 - 1.11 ( m, 2H) 1.21 (t, J=6.8 Hz. 3H) 1.37 - 1.44 (m. 2H) 4.14 (q, J=7.1 Hz, 2H) 4.57 (s, 2H) 7.14 (d. J=8.0 Hz, 2H 7.25 - 7.50 (m, 8H) 8.57 (s, 2H) MS (ESIJ: 517 (M+1), 515CM-1) 〇Ύ^°, β RA RB 304 4-F - PhCH2 H 1H NMR (300 MHz , DMSO-D6) δ ppm 1.76 - 2.12 (m, 4 H) 2.29 -2.47 (m, 2 H) 3.66 (s. 2 H) 4.53 (s, 2 H) 6.86 (d. J=8.7 Hz, 1 H 7.09 - 7.23 (m, 2 H) 7.30 - 7.44 (m, 2 H) 7.54 - 7.75 (m, 4 H) 7.97 (dd, J=8.7, 2.6 Hz, 1 H) 8.37 - 8.49 (m, 1 H) 10.27 (s. 1 H) 12.29 - 12.47 (br, 1 H) MS (ES1/APCI Dua丨): 435 (M+1), 433 (M-1) 305 3-Me - 4-F-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.83 - 2.15 (m, 4H) 2.32 - 2.50 (m, 2H) 2.35 (s, 3H) 4.55 (s. 2H) 6.89 (d. J = 8.6 Hz. 1H) 7.32 (t J=9.1 Hz, 1H) 7.68 (d, -J=8.6 Hz, 2H) 7.82 - 7.91 (m, 3H) 7.94 (d. J =7.7 Hz. 1H) 8.02 (dd, J=2.4 Hz. 8.6 Hz, 1H) 8.49 (d. J=2.7 Hz, 1H) 10.32 (s, 1H) 12.40 (s, 1H) MS(ESI): 435CM+ 1), 433CM-1) 306 3—F - 4-Me - Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.83 ~ 2.15 (m, 4H) 2.30 -2.45 (m, 2H) 2.33 (s, 3H) 4.54 (s, 2H) 6.88 (d. J=8.6 Hz, 1H) 7.47 (dd. J=7 7 Hz. 7.7 Hz. 1H) 7.67 (d. J=8.3 Hz, 2H) 7.76 (d, J =9.2 Hz, 2H) 7.87 (d, J=8.6 Hz, 2H) 8.00 (dd, J=2.5 Hz, 8.5 Hz. 1H) 8.48 (d, J=2.7 Hz, 1H) 10.32 (s. 1H) 12.30 - 12.53 (br, 1H) MS (ESI): 435 (M+1) 433 (M-1) -287 - 200918053 [Table 1-28] 307 3-CF3-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.82 - 2.15 Cm, 4H) 2.31 -2.48 (m, 2H) 4.56 (s, 2H) 6.90 (d, J=8.6 Hz. 1H) 7.65 - 7.80 (m. 3H) 7.87 (d, J =8.6 Hz, 2H) 8.03 (dd, J=3.0 Hz. 8.6 Hz, 1H) 8.33 -8.42 Cm. 2H) 8.50 Cd, J=2.4 Hz, 1H) 10.58 (s, 1H) 12.40 (s, 1H) MS (ESI): 489(M+1), 487CM-1) 308 2-MeO-4-CF3-Ph H 1H NMR (300 MHz. DMSO-D6) &lt;5 ppm 1.82 - 2.13 (m, 4H) 2.31 -2.47 (m, 2H) 3.97 (s, 3H) 4.55 (s, 2H) 6.90 (d, J=8.9 Hz. 1H) 7.44 (d, J=8.3 Hz, 1H) 7.48 (s, 1H) 7.67 (d, J=8.6 Hz, 2H) 7.77 (d, J=7.7 Hz, 1H) 7.82 (d, J=8.3 Hz, 2H) 8.01 (dd, J=2.7 Hz. 8.6 Hz. 1H) 8.49 (d. J=2.7 Hz. 1H) 10.39 (s, 1H) 12.39 Cs. 1H) MSCESI): 501CM+1), 499(M-1) 309 3f5-diF-Ph H 1H NMR (300 MHz, DMSO-D6) (5ppm 1.82 - 2.15 (m, 4H) 2.32 -2.48 (m. 2H) 4.55 (s. 2H) 6.90 (d. J=8.6 Hz.丨H) 7.50 - 7.62 ( m, 1H) 7.65 - 7.78 (m, 4H) 7.88 (d, J=8.6 Hz, 2H) 8.03 (dd, J=2.4 Hz, 8.6 Hz, 1H) 8.50 (d, J=2.4 Hz. 1H) 10.46 ( s. 1H) 12.40 (s, 1H) MSCESI): 439CM+1), 437 (M-1) 310 H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.81-2.15 (m, 4H) 2.3l-2.50 ( m, 2H) 4.55 (s, 2H) 6.90 (d, J=8.6 Hz, 1H) 7.61 (d, J=8.3 Hz, 1H) 7.69 (d, J=8.6 Hz, 2H) 7.87 (d, J=8.6 Hz, 2H) 7.91 (dd. J=1.6 Hz. 8.5 Hz, 1H) 7.99 - 8.10 (m, 2H) 8.50 (d, J=2.7 Hz. 1H) 10.39 (s, 1H) 12.27 - 12.52 (br. 1H) MSCESI): 483CM+1), 48KM-1) 311 2-MeO-3-CF3-Ph H 1H NMR ¢300 MHz, DMSO-D6) 6 ppm 1.83 - 2.10 (m, 4 H) 2.30 -2.44 (m, 2H) 3.84 (s, 3H) 4.53 (s, 2H) 6.88 (d. J=8.7 Hz, 1H) 7.40 (dd, J=7.8 Hz, 7.8 Hz. 1H) 7.67 (d J=8.7 Hz, 2H) 7.78 - 7.87 (m, 4H) 7.99 (dd, J=2.6 Hz. 8.6 Hz, 1H) 8.47 (d, J=2.4 Hz, 1H) 10.63 (s, 1H) 12.32 - 12.45 (br, 1H) MS (ESI): 501 (M+1) 499 (M-1) 312 2,3-diF-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.80 - 2.12 (m, 4H) 2.30 -2.45 (m. 2H) 4.54 (s, 2H) 6.89 (d, J=8.7 Hz, 1H) 7.30 - 7.41 (m, 1H) 7.46 - 7.56 (m, 1H) 7.56 - 7.72 (m, 1H) 7.68 (d, J=8.6 Hz, 2H) 7.81 (d, J=8.7 Hz, 2H) 8.01 (dd. J=2.4 Hz, 8.4 Hz, 1H) 8.48 (d, J=2.4 Hz, 1H) 10.65 ( s, 1H) 12.38 (s. 1H&gt; MSCESI): 439CM+1) 437(M-1) 313 2-Me〇-5-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.82 - 2.10 Cm, 4H) 2-30 -2.45 (m, 2H) 3.96 (s. 3H) 4.53 (s, 2H) 6.87 (d, J=8.4 Hz, 1H) 7.38 (d, J=8.1 Hz, 1H) 7.66 ( d, J=8.7 Hz, 2H) 7.81 (d, J=8.7 Hz, 2H) 7.84 - 7.91 (m. 2H) 8.00 (dd, J=2.7 Hz, 8.7 Hz, 1H) 8.47 (d, J=2.7 Hz , 1H) 10.34 (s, 1H) 12.31 - 12.43 Cbr, 1H) MS (ESI): 501 (M+1) 499 (M-1) 314 3-CF30-Ph H 1H NMR (3UU MHz, DMSO-D6) 0'ppm 1.80 - 2.09 (m, 4H) 2.28 -2.45 (m, 2H) 4.53 (s, 2H) 6.87 (d, J=8.3 Hz, 1H) 7.58 - 7.72 (m, 4H) 7.86 ( d, J=8.6 Hz, 2H) 7.91 (s, 1H) 7.98 - 8.05 (m, 2H) 8.47 (d. J=2.4 Hz, 1H) 10.46 (s. 1H) 12.20 - 12.53 (br, 1H) MSCESI) ; 487CM+1), 485(M-1) 315 2-CI-4,5-diF-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.80-2.21 Cm. 4H) 2.28 -2.46 (m 2H) 4.54 (s, 2H) 6.89 (d. J=8.3 Hz, 1H) 7.68 Cd, J=8.6 Hz, 2H) 7.79 (d, J=8.4 Hz, 2H) 7.85 - 7.96 (m, 2H) 8.00 (dd, J=2.5 Hz, 8.8 Hz, 1H) 8.48 Cd, J=2.4 Hz. 1H) 10.66 (s, 1H) 12.38 (s, 1H) MS(ESI): 473CM+1) 47KM-1) 316 3 -C 卜 4-Me-Ph H 1H NMRC300 MHz, DMSO-D6) 5ppm 1.80 - 2.10 (m, 4H) 2.31 -2.43 (m, 2H) 2.41 (s, 3H) 4.53 (s, 2H) 6.87 (d, J=8.9 Hz. 1H) 7.52 (d, J=8.3 Hz, 1H) 7.66 (d. J=8.6 Hz, 2H) 7.86 (d, J=8.3 Hz, 3H) 8.00 (dd, J=2.4 Hz, 8.6 Hz, 1H) 8.02 (d, J=1.8 Kz, 1H) 8.47 (d. J=2.4 Hz, 1H) 10.36 (s, 1H) 12.10 - 12.60 (br, 1H) MSCESl): 451 (M+1), 449(M-1) 317 3-F-Ph H 1H NMR ¢300 MHz, DMSO-D6) dppm 1.80 - 2.15 (m, 4H) 2-30 -2.45 (m, 2H) 4.5 4 (s. 2H) 6.89 (d, J=8.3 Hz. 1H) 7.47 (td, J=2.6 Hz, 8.6 Hz, 1H) 7.53 - 7.73 (m, 1H) 7.68 (d, J=8.6 Hz. 2H) 7.75 -7.93 (m, 2H) 7.88 (d. J=8.9 Hz. 2H) 8.02 (dd, J=2.5 Hz. 8.5 Hz, 1H) 8.49 (d, J=2.4 Hz, 1H) 10.41 (s, 1H) 12.38 (s, 1H) MS (ESI): 421CM+1) 419 (M-1) 318 3-CF2HCF20-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.80 - 2.10 (m. 4H) 2.30 - 2.44 (m, 2H) 4.53 (s. 2H) 6.66 - 7.05 (m, 2H) 7.53 (d, J=8.0 Hz, 1H) 7.62 - 7.71 (m. 1H) 7.67 (d, J=B.3 Hz. 2H) 7.86 (d, J=8.6 Hz, 3H) 7.96 - 8 03 (m, 2H) 8.47 (d. J=2.4 Hz. 1H) 10.46 (s, 1H) 12.25 -12.48 (br, 1H) MSCESI): 519CM+1), 517(M-1) 319 3,4-diMeO-Ph H 1H NMR ¢300 MHz, DMSO-D6) 5ppm 1.80 - 2.15 Cm, 4H) 2.32 - 2.47 (m, 2H) 3.86 (s, 3H) 3.87 (s, 3H) 4.55 (s, 2H) 6.89 (d. J=8.3 Hz. 1H) 7.11 (d, J=8.3 Hz, 1H) 7.56 (d, J=2.1 Hz, 1H) 7.62 - 7.72 (m. ΊΗ) 7.68 (d, J=8.0 Hz. 2H) 7.88 (d, J=8.9 Hz, 2H) 8.02 (dd, J=2.5 Hz, 8.5 Hz. 1H) 8.50 (d, J=2.4 Hz, 1H) 10.18 (s, 1H) 12.33 - 12.47 (br, 1H) 320 3__Me - 4 -MeO-Ph H 1H NMR (300 MHz, DMSO-D6) δ pp m 1.83 - 2.12 (m, 4H) 2.32 -2 45 (m. 2H) 2.41 (s, 3H) 3.88 (s, 3H) 4.54 (s, 2H) 6.88 (d, J=8.4 Hz, 1H) 7.08 (d , J=8.7 Hz, 1H) 7.66 (d, J=8.7 Hz, 2H) 7.80 - 7.92 (m. 2H) 7.88 (d, J=8.7 Hz, 2H) 8.01 (dd, J=2.4 Hz. 8.7 Hz, 1H) 8.48 (d, J=2.7 Hz, 1H) 10.15 (ε, 1H) 12.40 (s, 1H) MSCESI): 447 (M+1) 445 (M-1) -288- 200918053 [Table 1-29] RA RB 321 3-CI-4-Me-Ph H 1H NMR ¢300 MHz, DMS0-D6) δ ppm 1.82 - 2.15 (m, 4H) 2.35 -2.47 (m, 2H) 2.44 (s. 3H) 4.56 (s , 2H) 6.91 (d, J=8.6 Hz, 1H) 7.52 - 7.59 (m. 2H) 7.64 - 7.74 (m. 2H) 7.89 (d. J=8.3 Hz. 1H) 8.06 (s. 1H) 8.09 (dd J=2.5 Hz. 8.8 Hz, 1H) 8.57 (s, 1H) 10.25 (s, 1H) 12.32 - 12.48 (br. 1H) MS(ESI): 469 (M+1), 467 (M-1) rr0 -^ JUC^ H RA RB 322 3,4-diEt-Ph H 1H NMR (300 MHz, DMS0-D6) 5 ppm 1.16 - 1.27 Cm, 6 H) 1.77 -2.13 (m. 4 H) 2.22 - 2.44 (m , 2 H) 2.64 - 2.76 (m. 4 H) 4.54 (s, 2 H) 6.80 - 6.94 (m. 1 H) 7.32 (d, J=7.8 Hz, 1 H) 7.58 - 7.72 (m, 2 H) 7.72 - 7.81 (m, 2 H) 7.83 - 7.94 (m, 2 H) 8.01 (dd, J=8.7t 2.6 Hz, 1 H) 8.41 - 8.54 (m, 1 H) 10.22 (s, 1 H) 12.17 - 12.60 (br, 1 H) MS (ESI/APCI Dual): 457 (M-1) 323 3-F-4-C 卜 Ph H 1H NMR ( 300 MHz, DMS0-D6) 6 ppm 1.75 - 2.14 (m, 4 H) 2.30 -2.45 (m. 2 H) 4.54 (s, 2 H) 6.89 (d, J=8.7 Hz, 1 H) 7.61 - 7.75 ( m, 2 H) 7.75 - 7.93 (m, 4 H) 7.95 - 8.08 (m, 2 H) 8.49 (d, J=2.6 Hz, 1 H) 10.46 (s, 1 H) 12.26 - 12.51 (br, 1 H) MS (ESI/APCI Dual): 453 (M-1) 324 3-F-4-CF3~Ph H 1H NMR (300 MHz, DMS0-D6) (5 ppm 1.80 - 2.09 (m, 4H) 2.31 -2 ,44 (m, 2H) 4.53 (s, 2H) 6.87 (d, J=8.6 Hz. 1H) 7.69 (d, J=8.6 Hz, 2H) 7.86 (d, J=8.6 Hz. 2H) 7.95 - 8.09 ( m. 4H) 8.48 (d, J=2.1 Hz, 1H) 10.58 (s. 1H) 12.27 - 12.46 (br. 1H) MSCESO: 489CM+T), 487(M-1) 325 3-a-Ph H 1H NMR (300 MHz, DMS0-D6) ppm 1.85 - 2.13 (m, 4H) 2.30 -2.45 (m, 2H) 4.54 (s. 2H) 6.88 (d, J=9.2 Hz, 1H) 7.58 (dd, J=7.7 Hz, 8.3 Hz, 1H) 7.67 (d. J=8.6 Hz, 3H) 7.87 (d, J=8.6 Hz, 2H) 7.93 (d. J=7.2 Hz, 1H) 7.98 - 8.07 (m. 2H) 8.48 ( d. J=2.4 Hz, 1H) 10.44 (s. 1H) 12.38 (s, 1H) MS (ESI): 437 (M+1) 435 (M-1) 326 3 - GF3_Ph H 1H NMR (300 MHz, DMS0-D6) fi ppm 1.80 - 2.10 (m, 4H) 2.31 -2.45 (m, 2H) 4.53 (s, 2H) 6.87 (d, J=8.9 Hz. 1H) 7.68 (d, J=8.6 Hz, 2H) 7.79 (t J=8.0 Hz, 1H) 7.87 (d, J=8.6 Hz, 2H) 7.97 (d. J=8.0 Hz, 1H) 8.00 (dd, J=2.4 Hz, 8.9 Hz, 1H) 8.24 - 8.32 (m. 2H) 8.48 (d, J=2.7 Hz, 1H) 10.56 (s, 1H) 12.10 - 12.61 (br, 1H) MS (ESI): 47KM+1). 469CM-1) 327 2-CF3- 4-F-Ph H 1 H NMR ¢300 MHz, DMS0-D6) (5 ppm 1.79 - 2.10 (m, 4H) 2.30 -2.44 (m, 2H) 4.53 (s, 2H) 6.87 (d. J=8.3 Hz 1H) 7.61 - 7.85 (m, 7H) 7.98 (dd, J=2.7 Hz. 8.6 Hz, 1H) 8.45 (d, J=2.4 Hz. 1H) 10.66 (s. 1H) 12.10 - 12.60 (br. 1H) MSCESO: 489CM+1), 487CM-1) 328 3,5-diCKPh H 1H NMR (300 MHz, DMS0-D6) 5ppm 1.80 - 2.12 (m, 4H) 2.27 -2.48 (m, 2H) 4.54 (s, 2H 6.89 (d. J=8.3 Hz. 1H) 7.69 (dt J=8.9 Hz, 2H) 7.82 - 7.94 (m, 3H) 7.96 - 8.06 (m, 3H) 8.49 (d. J=2'7 Hz, 1H 10.52 (s, 1H) 12-38 (s, 1H) MS (ESI): 47ΚΜ+Ί) 469(H) 329 2,5-diF-Ph H 1H NMR (300 MHz, DMS0-D6) 5ppm 1.78 - 2.15 (m. 4H) 2.30 -2.44 (m, 2H) 4.53 (s, 2H) 6.87 (d, J=8.6 Hz, 1H) 7.40 - 7.50 (m. 2H) 7.50 - 7.60 (m, 1H) 7.66 (d, J=8.3 Hz, 2H) 7.79 (d, J=8.6 Hz, 2H) 7.99 (dd, J=2.5 Hz, 8.5 Hz, 1H) 8.46 (d. J=2.4 Hz, 1H) 10.58 (s, 1H) 12.00 - 12.75 (br, 1H) MSCESO: 439(M+1), 437CM-1) 330 2_MeO-4-F-Ph H 1H NMR (300 MHz, DMS0-D6) $ ppm 1.85 - 2.15 (m, 4H) 2.30 -2.47 2H) 3.94 (&, 3H) 4 55 U 2H) 6 89 (d. J=8 6 Hz, 1H) 6.85 - 7.00 ( m. \H) 7.12 (d, J=11.6 Hz. 1H) 7.66 (d, J=8.6 Hz, 2H) 7.72 (dd, J=7.4 Hz, 8 0 Hz, 1H) 7 83 (d, J=8.6 Hz, 2H) 8.01 (dd, J=2.7 Hz, 8.6 Hz, 1H) 8.48 (d. J=2.4 Hz, 1H) 10.16 (s, 1H) 12.39 (s, 1H) MS(ESI): 451 (M+ 1) 449 (M-1J 331 3,4-diF-Ph H 1H NMR (300 MHz, DMS0-D6) δ ppm 1.83 - 2.10 (m, 4H) 2.32 -2.45 (m, 2H) 4.54 (s. 2H) 6.89 (d, J=8.7 Hz. 1H) 7.58 - 7.73 (m. 1H) 7.69 (d, J=9.0 Hz, 2H) 7.83 - 7.93 (m, 1H) 7.86 (d, J=9.0 Hz, 2H) 8.02 (dd. J=2.7 Hz, 8.7 Hz. 1H) 8.02 - 8.10 (m. 1H) 8.49 (d, J=2.1 Hz, 1H) 10.42 (s, 1H) 12.40 (s, 1H) MS(ESi): 439 (M+1) 437 (M-1) -289- 200918053 [Table 1 - 3 0] 332 4-CF30-Ph H 1H NMR ¢300 MHz, DMSO-D6) (5ppm 1.80 - 2.09 (m, 4H) 2.30 - 2.45 (m, 2H) 4.53 (s. 2H) 6.88 (d, J=8.4 Hz, 1H) 7.54 (d, J=8.7 Hz. 2H) 7.67 (d, J=8.7 Hz , 2H) 7.86 (d, J=8.1 Hz. 2H) 8.00 (dd, J=2.0 Hz, 8.6 Hz. 1H) 8.09 (d. J=8.4 Hz, 2H) 8.48 (d. J=2.4 Hz. 1H) 10.45 (s. 1H) 12.30 - 12.45 Cbr. 1H) MS (ESI): 487 (M+1), 485 (M-1) 333 3-MeO-Ph H 1H NMR (300 MHz, DMSO-D6) &lt;5 ppm 1.85 - 2.10 Cm, 4H) 2.30 -2.45 (m, 2H) 3.85 (s, 3H) 4.54 (s. 2H) 6.89 (d, J=8.4 Hz, 1H) 7.17 (dd, J=2.7 Hz , 8.1 Hz, tH) 7.46 (dd, J=7.8 Hz, 8.1 Hz, 1K) 7.49 - 7.52 (m, 1H) 7.56 (d, J=7.8 Hz. 1H) 7.67 (d, J=8.4 Hz. 2H) 7.89 (d, J=9.0 Hz. 2H) 8.02 (dd. J=2.7 Hz, 9.0 Hz, 1H) 8.49 (d, J=2.7 Hz, 1H) 10.32 (s. 1H) 12.40 (s, 1H) MSCESI) : 433 (M+1) 431 (M-1) 334 3-Me-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.82 - 2.10 Cm, 4H) 2.23 (s. 3H) 2.25 - 2.50 (m , 2H) 4.54 (s, 2H) 6.89 (d. J=8.7 Hz, 1H) 7.38 - 7.47 (m. 2H) 7.67 (d. J=8.7 Hz, 2H) 7.72 - 7.82 (m, 2H) 7.89 (d J=8.7 Hz, 2H) 8.01 (dd, J=2.6 Hz. 8.6 Hz, 1H) 8.49 (d, J=2.7 Hz, 1H) 10.32 (s, 1H) 12.40 (s, 1H) MS(ESl): 417 (M+1) 415 (M-1) 0 丫, Η RA RB 335 3-CF3-Ph H 1H NMR (300 MHz, DMSOO6) (5ppm 1.80 - 2.14 (m, 4H) 2.30 -2.45 (m, 2H 4.55 (s, 2H) 6.92 (d, J=8.3 Hz. 1H) 7.59 (t J=8.6 Hz, 1H) 7.68 (dd, J=2.1 Hz, 8.3 Hz, 1H) 7.77 - 7.96 (m. 3H) 8.01 Cd. J=8.0 Hz. 1H) 8.25 - 8.42 Cm, 3H) 10.74 (s, 1H) 12.40 (s, 1H) MSCESI): 489CM+1) 487 (M-1J.丫〇, "B f RA RB 336 3-CF3-Ph H 1H NMR ¢ 300 MHz, DMSO-D6) δ ppm 1.81 - 2.11 Cm, 4H) 2.32 -2.45 (m, 2H) 4.56 (s, 2H) 6.91 ( d, J=8.7 Hz, 1H) 7.57 (d, J=8.4 Hz, 1H) 7.62 - 7.75 (m, 2H) 7.80 (t. J=7.8 Hz, 1H) 8.00 (d, J=7.8 Hz, 1H) 8.08 (dd. J=2.6 Hz. 8.9 Hz, 1H) 8.29 (d. J=7.7 Hz, 1H) 8.33 (s, 1H) 8.b6 (d, J=2A Hz. 1HJ 10.48 (s, 1H) 11.90 - 13.00 (br. 1H) MS (ESI): 489CM+1). 487CM-1) rr°^ H RA RB 337 3,4-diC 卜 Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.72 - 2.13 (m, 4 H) 2.24 -2.47 (m, 2 H) 4.54 (s, 2 H) 6.81 - 6.94 (m. 1 H) 7.61 - 7.75 (m, 2 H) 7.79 7.92 (m, 3 H) 7.92 - 8.06 (m, 2 H) 8_24 (d, J=2.0 Hz. 1 H) 8.44 - 8.53 (m, 1 H) 10.49 (s. 1 H) 12.24 - 12.56 (br, 1 H) MS (ESI/APCI Dual): 469 (M-1) 338 2,3-diMe-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.01 - 1.53 Cm, 5 H) 1.54 -2.12 (m, 9 H) 2.22 - 2.45 (m, 3 H) 4.53 (s, 2 H) 6.79 - 6.91 (m. 1 H) 7.49 - 7.64 (m. 2 H) 7.64 - 7.76 (m, 2 H) 7.96 (dd, J=8.6t 2.6 Hz , 1 H) 8.37 - 8.49 Cm, 1 H) 9.89 (s, 1 H) 12.23 - 12.57 (b r, 1 H) MS (ESI/APCI Dual): 429 (M-1) 339 cycloHexyl H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.01 - 1.53 Cm. 5 H) 1.54 -2.12 (m. 9 H 2.22 - 2.45 (m. 3 H) 4.53 (s. 2 H) 6.79 - 6.91 (m, 1 H) 7.49 - 7.64 (m. 2 H) 7.64 - 7.76 (m. 2 H) 7.96 (dd, J= 8.6, 2.6 Hz_ 1 H) 8.37 - 8.49 (m. 1 H) 9.89 (s, 彳H) 12.23 - 12.57 (br, 1 H) MS (ESI/APCI Dual): 407 (M-1) 340 2 - naphthyl H 1H NMR ¢ 300 MHz. DMSO-D6) 6 ppm 1.79 - 2.13 Cm, 4 H) 2.32 -2.43 (m, 2 H) 4.54 (s, 2 H) 6.89 (dt J=8.6 Hz, 1 H) 7.62 - 7.74 (mt 4 H) 7.95 (d, J=6.8 Hz, 2 H) 7.99 - 8.17 (m, 5 H) 8.50 (d, J=2.3 Hz, ί H) 8.61 (s, 1 H) 10.54 (s, 2 H) MS (ESI/APCI Dual): 453 (M+1) 341 3-CI-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.79 - 2.12 Cm, 4 H) 2.32 - 2.44 (m. 2 H) 4.54 (s. 2 H) 6.89 (d, J=9.0 Hz, 1 H) 7.56 - 7.73 (m. 3 H) 7.87 (d. J=8.7 Hz, 2 H) 7.96 - 8.08 (m. 2 H) 8.23 (dd. J=7.0, 2.3 Hz, 1 H) 8.49 (d, J=2.3 Hz, \ H) (0.45 (s, 1 H) MS (ESI/APCI Dual): 455 ( M+1). 453 (M-1) -290- 200918053 [Table 1-31] 342 3,4-diMe-Ph H 1H NMR (300 MH z, DMSO-D6) ¢5 ppm 1.80 - 2.13 (m, 4 H) 2.26 -2.35 (m, 6 H) 2.35 ^ 2.44 (m, 2 H) 4.54 (s, 2 H) 6.88 (d, J=8.6 Hz, 1 H) 7.30 (d. J=7.9 Hz, 1 H) 7.61 - 7.81 (m. 4 H) 7.84 - 7.94 (m, 2 H) 8.01 (dd, J=8.7, 2.6 Hz, 1 H) 8.48 (d. J=2.6 Hz, 1 H) 10.22 Cs, 1 H) MS (ESI/APCI Dual): 431 (M+1), 429 CM-1) 343 Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.81 - 2.12 Cm, 4 H) 2.34 ' 2.44 Cm, 2 H) 4.54 (s, 2 H) 6.88 (d, J=9.0 Hz. 1 H) 7.50 - 7.63 (m.3H)7.67(d,J =8.7 Hz, 2H) 7.89 (d, J = 8.7 Hz. 2H) 7.94 - 8.05 (m, 3 H) 8.49 (d, J = 2.5 Hz, H) 10.35 (s. 1 H) 12.34 - 12.43 (br, 1 H) MS (ESI/APCI Dual): 403 (M+1). 401 CM-1) 344 4-Et-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.22 (t, J=7.6 Hz , 3 H) 1.82 - 2.11 (m. 4 H) 2.31 - 2.44 (m, 2 H) 2.70 (q, J=7.9 Hz, 2 H) 4.54 (s, 2 H) 6.88 (d, J=8.7 Hz. 1 H) 7.38 (d, J=8.2 Hz, 2 H) 7.66 (d, J=8.9 Hz. 2 H) 7.85 - 7.94 (m. 4 H) 8.01 (dd, J=8.6, 2.6 Hz, 1 H) 8.48 (d, J=2.6 Hz· 1 H) 10.26 (s. 1 H) MS (ESI/APCI Dual): 431 (M+1), 429 (M-1) 345 3-CF3-4-Me-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.71 - 2.16 Cm, 4 H) 2.22 -2.47 (m, 2 H) 2.49 - 2.62 (m. 3 H) 4.55 (s. 2 H) 6.89 (d. J=8.7 Hz, 1 H) 7.55 - 7.76 (m. 3 H) 7.82 - 7.95 (m. 2 H) 8.02 (dd, J=8.6. 2.6 Hz. 1 H) 8.11 - 8.23 (m, 1 H) 8.23 - 8.31 (m. 1 H) 8.49 (d J=2.6 Hz, 1 H) 10.50 Cs, 1 H) 12.22 - Ί2.56 (br, 1 H) MS CESI/APCI Dual): 485 CM+1). 483 CM-1) 346 2,4-diMe -Ph H 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.81 - 2.12 Cm, 4 H) 2.27 -2.46 (m, 2 H) 2.33 (s, 3 H) 2.37 (s, 3 H) 4.54 (s. 2 H) 6.84 - 6.91 (m, 1 H) 7.07 - 7.16 (m, 2 H) 7.38 (d, J = 7.5 Hz, 1 H) 7.59 - 7.69 (m, 2 H) 7.78 - 7.88 (m, 2 H 7.99 (dd, J=8.6, 2.6 Hz, 1 H) 8.45 -8.49 (m, 1 H) 10.30 Cs, 1 H) 12.24 - 12.53 (br, 1 H) MS CESI/APCI Dual): 429 CM-1 347 2,5-diMe-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.79 - 2.14 (m, 4 H) 2.23 -2.46 (m, 8 H) 4.54 (s. 2 H) 6.84 - 6.92 (m, 1 H) 7.15 - 7.25 Cm, 2 H) 7.29 (s, 1 H) 7.58 - 7.69 (m. 2 H) 7.77 - 7.89 (m, 2 H) 8.00 (dd. J=8.7. 2.6 Hz, 1 H) 8.43 - 8.51 (m, 1 H) 10.36 (s. 1 H) 12.27 -12.52 Cbr, 1 H) MS (ESI/APCI Dual): 429 (M-1) 348 3-Ph-Ph H 1H NMR (300 MHz. DMSO-D6) &lt;5 ppm 1.75 - 2.12 Cm, 4 H) 2.26 -2.47 (m, 2 H) 4.55 (s. 2 H) 6.89 (dt J=8.7 Hz. 1 H) 7.38 - 7.48 (m, 1 H) 7.48 - 7.58 (m. 2 H) 7.60 - 7.74 (m, 3 H) 7.74 - 7.83 (m, 2 H) 7.86 - 8.00 (m. 4 H) 8.03 (dd, J=8.6, 2.6 Hz, 1 H) 8.21 - 8.27 (m, 1 H) 8.50 (d. J=2.5 Hz. 1 H) 10.45 (s. 1 H) 12.12 - 12.63 (br, 1 H) MS (ESI/APCI Dual): 477 (M-1) 349 3f5-diMe~Ph H 1H NMR ¢300 MHz, DMSO-D6) d ppm 1.83 - 2.10 Cm, 4 H) 2.32 -2.45 (m, 8 H) 4.54 (s, 2 H) 6.88 (d, J=9.0 Hz 1 H) 7.23 (s, 1 H) 7.58 (s, 2 H) 7.66 (d, J=8.7 Hz. 2 H) 7.88 (d. J=8.7 Hz. 2 H) 8.01 (dd. J=8.6. 2.6 Hz. 1 H) 8.48 (d, J=3.1 Hz, 1 H) 10.26 (s. 1 H) 12.32 - 12.47 (br, 1 H) MS (ESI/APCI Dual): 431 CM+1). 429 ( M-1) 350 2,6-diMe-Ph H 1H NMR ¢300 MHz. DMSO-D6) 6 ppm 1.82 - 2.11 Cm, 4 H) 2.29 (s, 6 H) 2.32 - 2.45 (m, 2 H) 4.54 (s. 2 H) 6.85 - 6.92 (m, 1 H) 7.09 - 7.16 (m. 2 H) 7.19 - 7.29 (m. 1 H) 7.60 - 7.68 (m, 2 H) 7.79 - 7.88 (m· 2 H) ) 7.99 (dd, J=8.7. 2.6 Hz, 1 H) 8_43 - 8.49 (m, 1 Η) Ϊ0.47 (s, 1 H) 12.31 - 12.46 (br, 1 H) M S CESI/APCI Dua!): 431 (M+1), 429 CM-1) 351 3 - MeS02_Ph H 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.82 - 2.12 Cm, 4 H) 2.31 -2.44 (m 2 H) 3.31 (s. 3 H) 4.55 (s, 2 H) 6.89 (d, J=8.6 Hz. 1 H) 7.66 - 7.75 (m. 2 H) 7.80 - 7.92 (m. 3 H) 8.03 ( Dd. J=8.6, 2.6 Hz. 1 H) 8.12 - 8.19 (m, 1 H) 8.29 - 8.35 (m. 1 H) 8.45 - 8.55 (m, 2 H) 10.63 (s. 1 H) 12.33 ~ 12.46 ( Br. 1 H) MS (ESE/APCI Dual): 481 (M+1), 479 (M-1) 352 3-F-4-Me〇-Ph H 1H NMR ¢300 MHz, DMSO-D6) 6 ppm 1,81 - 2.12 Cm, 4 H) 2.31 -2.45 (mt 2 H) 3.94 (s, 3 H) 4.54 (s. 2 H) 6.85 - 6.91 (m. 1 H) 7.33 (t, J=8.6 Hz, 1 H) 7.62 - 7.71 (m, 2 H) 7.82 - 7.91 (m, 4 H) 8.01 (dd. J=8.6. 2.6 Hz. 1 H) 8.45 - 8.51 (m, 1 H) 10.24 (s. 1 H 12.31 - 12.46 (br, 1 H) MS CESI/APCI Dual): 451 (M+1). 449(M-1) 353 3-Me〇-4-Me-Ph H 1H NMR ¢300 MHz, DMSO- D6) δ ppm 1.80 * 2.13 (m, 4 H) 2.23 (s, 3 H) 2.31 - 2.44 (m, 2 H) 3.90 (s, 3 H) 4.54 (s, 2 H) 6.88 (d. J=8.4 Hz, 1 H) 7.31 (d, J 7.8 Hz, 1 H) 7.46 - 7.57 (m, 2 H) 7.67 (d. J=8.7 Hz. 2 H) 7.88 (d, J=8.7 Hz. 2 H) 8.0 2 (dd, J=8.6, 2.6 Hz, 1 H) 8.49 Cd, J=2.6 Hz. 1 H) 10.24 (s, 1 H) 12.38 (s, 1 H) MS (ESI/APCI Dual): 447 (MM ), 445 (M-1; 354 3-CI-4-MeO-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.79 - 2.12 (m, 4 H) 2.25 -2.45 (m. 2 H) 3.96 Cs, 3 H) 4.54 (s, 2 H) 6.88 (d. J=8.4 Hz. 1 H) 7.31 (d. J=8.9 Hz, 1 H) 7.67 (d, J=8.7 Hz, 2 H) 7.87 ( d. J=8.7 Hz, 2 H) 7.96 - 8.05 (m. 2 H) 8.11 (d. J=2.3 Hz, 1 H) 8.48 (d. J=2.3 Hz. 1 H) 10.28 (s, 1 H) 12.33 - 12.44 (br. 1 H) MS (ESI/APCI Dual): 467 (M+1), 465 (M-1) 355 3-Me-4-C 卜 Ph H 1H NMR (300 MHz, DMSO-D6 Fi ppm 1.81 - 2.12 (m, 4 H) 2.30 -2.47 (m, 5 H) 4.54 (s, 2 H) 6.88 (d. J=8.7 Hz, 1 H) 7.60 (d. J=8.4 Hz, 1 H) 7.67 (d, J=8.7 Hz, 2 H) 7.78 - 7.91 (m. 3 H) 7.97 (d. J=1.9 Hz, 1 H) 8.01 (dd, J=8.6, 2.6 Hz. 1 H) 8.48 (dt J=2.6 Hz. 1 H) 10.37 (s. 1 H) 12.31 - 12.44 (br, 1 H) MS (ESI/APCI Dual): 451 (M+1). 449 (M-1) -291 - 200918053 [表卜32] 356 00* H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.69 - 2.11 (m, 8 H) 2.29 -2.46 (m, 2 H) 2.72 - 2.87 (m, 4 H) 4.54 (s, 2 H) 6.88 (d, J=8.6 Hz, 1 H) 7.21 (d. J=8.6 Hz, 1 H) 7.61 - 7.74 (m, 4 H) 7.84 - 7.93 (m, 2 H) 8.01 (dd. J =8.7. 2.6 Hz, 1 H) 8.48 (d, J=2.5 Hz, 1 H) 10.21 (s. 1 H) 12.21 - 12.57 (br, 1 H) MS CES1/APCI Dual): 455 (MM) 357 3 -OH-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.77 - 2.14 Cm, 4 H) 2.29 -2.47 (m, 2 H) 4.54 (s, 2 H) 6.82 - 6.92 (m, 1 H) 6.98 (ddd, J=7.9. 2.4, 1.2 Hz. 1 H) 7.27 - 7.44 (m. 3 H) 7.59 - 7.72 (m. 2 H) 7.81 -7.92 (m, 2 H) 8.01 (dd, J=8.6 , 2.6 Hz, 1 H) 8.42 - 8.51 (m. 1 H) 9.76 (s, 1 H) 10.26 (s, 1 H) 12.38 (s, 1 H) MS CESI/APCI Dual): 417 (M-1) 358 3HPr - Ph H 1H NMR ¢300 MHz. DMSO-D6) 6 ppm 1.26 (s, 3 H) 1.28 (s, 3 H) 1.74 - 2.17 (m, 4 H) 2.23 - 2.48 (m. 2 H) 3.00 (m, 1 H) 4.55 (s, 2 H) 6.89 (d. J = 8.7 Hz, 1 H) 7.35 - 7.57 (m. 2 H) 7.58 - 7.73 (m, 2 H) 7.73 - 7.95 (m, 4 H) 8.02 (dd. J=8.6, 2.6 Hz, 1 H) 8.49 (d, J=2.6 Hz, 1 H) 10.30 (s, 1 H) 12.06 - 12.64 (br, 1 H) MS (ESI/APCI Dual ): 445 iM+1). 443 (M-1) 359 3-MeS-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.79 - 2.12 (m, 4 H) 2.26 -2.46 (m. 2 H) 2.56 (s. 3 H) 4.54 (s, 2 H) 6.89 (d, J=8.6 Hz. 1 H) 7.41 - 7.54 (m, 2 H) 7.61 - 7.77 ( m, 3 H) 7.77 - 7.83 (m, 1 H) 7.83 - 7.93 (m. 2 H) 8.02 (dd. J=8.7, 2.5 Hz, 1 H) 8.49 (d, J=2.6 Hz, 1 H) 10.37 (s, 1 H) 12.21 - 12.53 (br. 1 H) MS CESI/APCI Dual): 449 (M+1), 447 (M~1) 360 3-CF3-4-CI-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.79 - 2.14 (m, 4 H) 2.28 -2.47 (m. 2 H) 4.55 (s, 2 H) 6.84 - 6.94 (m. 1 H) 7.64 - 7.75 (m, 2 H 7.81 - 7.91 (m. 2 H) 7.94 (d. J=8.6 Hz. 1 H) 8.02 (dd, J=8.6, 2.6 Hz. 1 H) 8.29 (dd. J=8.3, 1.9 Hz, 1 H) 8.41 (d. J=2.0 Hz, 1 H) 8.45 - 8.55 Cm, 1 H) 10.62 (s, 1 H) 12.39 (s, 1 H) MS (ESI/APCI Dual): 505 (M+1), 503 (M-1) 361 3-CN-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.80 - 2.12 (m, 4 H) 2.31 -2.46 (m, 2 H) 4.55 (s. 2 H) 6.86 - 6.93 (m. 1 H) 7.65 - 7.73 (m. 2 H) 7.77 (t, J=7.9 Hz, 1 H) 7.84 - 7.93 (m, 2 Η) B.02 (dd. J=8.7, 2.6 Hz , 1 H) 8.09 (dt, J=7.8. 1.4 Hz, 1 H) 8.24 - 8.31 (m. 1 H) 8.41 -8.45 (m, 1 H) 8.47 - 8.52 (m, 1 H) 10.53 (s, 1 H) 11.66 - 12.91 (br, 1 H) MS CESI/APCI Dual): 426 (M-1) 丫, RB r^Y0^ O RA RB 362 3-CF30-Ph H 1H NMR (300 MHz, DMSO-D6) t5ppm 0.97 - 1.09 Cm, 2H) 1.15 -1.26 (m, 2H) 4.40 (s. 2H) 6.91 (d, J=8.6 Hz. 1H) 7.59 - 7.75 (m, 4H) 7.87 (d. J=8.6 Hz. 2H) 7.93 (s. 1H) 7.97 - 8.08 (σι, 2H) 8.47 (d, J=2.4 Hz, 1H) 10.49 (s. 1H) 12.35 - 12.42 (br, 1H) MSCESI): 473CM+1) 47KM-1) 363 3-Me-4-F-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.04 (q. J=3.7 Hz, 2H) 1.17 - 1.23 (m, 2H) 2.33 (s. 3H) 4.39 ( s, 2H) 6.90 (d, J=8.6 Hz. 1H) 7.31 (dd, J=8.6 Hz. 9.5 Hz, 1H) 7.66 (d, J=8.9 Hz. 2H) 7.80 -7.90 (m. 1H) 7.86 ( d. J=8.9 Hz. 2H) 7.93 (d. J=7.7 Hz, 1H) 8.00 (dd. J= 2.8 Hz. 8.8 Hz, 1H) 8.45 (d, J=2.4 Hz. 1H) 10.31 (s, 1H 12.38 (st 1H) MS (ESI &gt;. 421 (M+1) 419 (M-1) 364 3-CI-4-Me-Ph H 1H NMR (300 MHz, DMSO-D6) fippm 0.98 - 1.05 (m , 2H) 1.15 -1.22 (m. 2H) 2.42 (s. 3H) 4.39 (s. 2H) 6.90 (d. J=8.6 Hz. 1H) 7.53 (d, J=8.3 Hz, 1H) 7.66 (d, J =8.9 Hz. 2H) 7.87 (d, J=8.0 Hz, 3H) 8.00 (dd. J=2.5 Hz. 8.8 Hz, 1H) 8.04 (s, 1H) 8.45 (d, J = 2.7 Hz. 1H) 10.37 (s. 1H) MSCESI): 437CM+1), 435(M-1) 365 3-CF3-4-C Ph Ph 1H NMR (300 MHz. DMSO-D6J δ ppm 0.99 - 1.08 Cm, 2 H) 1.16 -1.26 (m, 2 H) 4.40 (s, 2 H) 6.91 (d. J=8.7 Hz, 1 H) 7.70 (d, J=8.7 Hz, 2 H) 7.86 (d. J=8.7 Hz, 2 H) 7.95 (d. J=8.4 Hz. 1 H) 8.02 (dd. J=8.8, 2.6 Hz, 1 H) 8.29 (dd, J=7,7 , 1,5 Hz, 1 H) 8.41 (d, J=2.0 Hz, 1 H) 8.47 (d, J=2.6 Hz, 1 H) 10.62 Cs, 1 H) 12.38 Cs, 1 H) MS (ESI/APCI) Dual): 491 (M+1). 489 (M-1) 366 3-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) c5ppm 1.00 - 1.05 (m. 2H) 1.15 -1.22 (m. 2H) 4.38 (s. 2H) 6.90 (d, J=9.3 Hz. 1H) 7.67 (d. J=8.7 Hz. 2H) 7.79 (t. J=7.8 Hz, 1H) 7.86 (d. J^8.7 Hz, 2H) 7.94 - 8.03 (m. 2H) 8.23 - 8.30 (m. 2H) 8.45 (d, J=3.0 Hz. 1H) 10.55 (s, 1H) 12.25 -12.50 (br, 1H) MSiESI): 457 (M+1) , 455(M-1) 367 3,4-diCkPh H 1H NMR (300 MHz, DMSO-D6) δ ppm 0.48 - 0.61 (m, 2 H) 0.85 -0.95 (m. 2 H) 4.41 (s, 2 H 6.81 (d, J=8.7 Hz, 1 H) 7.65 (d, J=8.7 Hz, 2 H) 7.80 - 7.91 (m, 3 H) 7.92 - 8.04 (m. 2 H) 8.26 (s. 1 H) 8.43 (s. 1 H) 1 0-63 (5.11 H) MS CESI/APCI Dual): 457 (M+1). 455 (M-1) -292 - 200918053 [Table 34] 368 3,4-diMe-Ph H 1H NMR ( 300 MHz, DMSO-D6) δ ppm 0.94 - 1.10 (m, 2 H) 1.13 -1.28 (m, 2 H) 2.24 - 2.37 (m. 6 H) 4.40 (s, 2 H) 6.90 (d, J=8.6 Hz. 1 H) 7.30 (d. J=7.9 Hz. 1 H) 7.58 - 7.80 (m. 4 H) 7.84 - 7.92 (m, 2 H) 8.00 (d. J=8.7 Hz, 1 H) 8.45 (d , J=2.5 Hz, 1 H) 10.21 (s, 1 H) 12.27 - 12.44 (br. 1 H) MS (ESI/APCI Dual): 417 (M+1), 415 (M-1) 369 3-C 4-F-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 0.98 - 1.10 (m, 2 Η) M6 -1.25 (m. 2 H) 4.40 (s, 2 H) 6.91 (d, J= 8.7 Hz. 1 H) 7.54 - 7.75 (m. 3 H) 7.86 (d. J=8.7 Hz, 2 H) 7.94 - 8.07 (m, 2 H) 8.22 (dd, J=7.2. 2.2 Hz, 1 H) 8.46 (d, J=2.5 Hz, 1 H) 10.44 (s. 1 H) 12.31 -12.41 (br, 1 H) MS (ES1/APCJ Dual): 441 (M+1), 439 (M-1) 370 3,5-diMe-Ph H 1H NMR C300 MHz, DMSO-D6) δ ppm 1.00 - 1.08 (m, 2 H) 1.16 -1.25 (m. 2 H) 2.37 (s, 6 H) 4.40 (s, 2 H 6.86 - 6.94 (m, 1 H) 7.20 - 7.26 (mt 1 H) 7.54 - 7.60 (m, 2 H) 7.61 - 7.70 (m, 2 H) 7.83 - 7.92 (m, 2 H) 8.00 (dd J=8.6, 2.6 Hz, 1 H) 8.42 - 8.48 (m, 1 H) 10.26 (s. 1 H) 12.21 - 12.55 (br, 1 H) MS (ESI/APCI Dual): 415 (M-1) 371 CO* H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 0.98 - 1.08 (m, 2 H) 1.16 -1.25 (m. 2 H) 1.69 - 1.84 (m. 4 H) 2.71 - 2.88 (m, 4 H) 4.40 (st 2 H) 6.90 (d. J=8.6 Hz, 1 H) 7.16 - 7.26 (m, 1 Η) 7·60 - 7.74 (m, 4 H) 7.84 - 7.92 (m, 2 H) 8.00 (dd. J=8.6, 2.5 Hz, 1 H) 8.45 (d. J=2.6 Hz, 1 H) 10.22 (s, 1 H) 12.19 - 12.54 (br. 1 H) MS (ESI/APCI Dual): 443 (M+1), 441 (M-1) 372 3-iPr-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.00 - 1.08 (m, 2 H) 1.17 -1.24 (m, 2 H) 1.26 (s. 3 H) 1.28 (s. 3 H) 2.92 - 3.08 (m, 1 H) 4.40 (s, 2 H) 6.87 - 6.95 (m. 1 H) 7.41 - 7.52 (m. 2 H) 7.61 - 7.71 (m. 2 H) 7.74 - 7.93 (m. 4 H) 8.01 (dd. J=8.6, 2.6 Hz, 1 H) 8.42 -8.50 (m, 1 H) 10.30 (s, 1 H) 11.76 — 13.02 (br , 1 H&gt; MS (ESI/APCI Dual): 431 (M+1), 429 (M-1) 373 3-C Bu 4-MeO-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 0.99 - 1.07 (m, 2 H) 1.16 -1.23 (m. 2 H) 3.96 (s, 3 H) 4.39 (s, 2 H) 6.90 (d, J=9.0 Hz. 1 H) 7.31 (d, J=9.0 Hz. 1 H) 7.66 (d, J=8.7 Hz, 2 H) 7.86 (d. J=8.7 Hz, 2 H) 7.96 - 8.04 (m. 2 H) 8.11 (d. J =2.0 Hz. 1 H) 8.45 (d. J=2.3 Hz, 1 H) 10.28 Cs, 1 H) 12.30 - 12.50 (br. 1 H) MS (ESI/APCI Dual): 453 (M+D. 451 ( M-1) D丫. '明RA RB 374 3-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.61 - 1.74 (m, 6H) 1.98 -2.12 (m. 2H) 4.36 (s, 2H) 6.88 (d. J =8.7 Hz. 1H) 7.69 (d, J=8.7 Hz, 2H) 7.81 (dd, J=7.5 Hz. 7.8 Hz. 1H) 7.88 Cd. J=8.4 Hz, 2H) 7.95 - 7.82 (m. 1H) 8.02 (dd. J=2.6 Hz· 8.5 Hz, 1H) 8.29 (d, J 9.6 Hz. 1H) 8.31 (s, 1H) 8.48 (d. J=2.7 Hz. 1H) 10.57 (s, 1H) 12.22 -12.40 (br. 1H) MSCES1): 485 (_) 483 (M-1) °^&gt;B JvC^ RA RB 375 3-CF3-4-C!-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ Ppm 1.23 Cs, 6 H) 4.29 Cs, 2 H) 6.89 (d, J=8.6 Hz, 1 H) 7.69 (d, J=8.7 Hz, 2 H) 7.87 (d. J=8.9 Hz, 2 H) 7.95 (d, J=8.2 Hz, 1 H) 8.02 (dd, J=8.7, 2.6 Hz, 1 H) 8.24 -8.33 (m, 1 H) 8.41 (d, J=2.0 Hz. 1 H) 8.48 (d. J=2.5 Hz, 1 H) 10.62 Cs, 1 H) 12.27 - 12.46 (br. 1 H) MS (ESI/APCI Dual): 493 CM+1). 491 (M-1) 376 3-C 卜 4- Me_Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.23 (s. 6 H) 2.42 (s, 3 H) 4.29 (s. 2 H) 6.88 (d. J=8.6 Hz, 1 H) 7.54 (d , J=7.9 Hz, 1 H) 7.67 (d. J=8.7 Hz, 2 H) 7.82 - 7.91 (m, 3 H) 7.96 - 8.07 (m, 2 H) 8.47 C d, J=2.5 Hz, 1 H) 10.37 (s, 1 H) 12.28 - 12.41 (br. 1 H) MS (ESI/APCI Dual): 439 CM+1). 437 (M-1) 377 3,4 -diCI-Ph H 1H NMR (300 MHz. DMSO-D6) &lt;5 ppm 1.23 (s. 6 H) 4.29 (s, 2 H) 6.88 (d. J=8.7 Hz, 1 H) 7.68 (d, J=8.7 Hz, 2 H) 7.80 - 7.90 (m, 3 H 7.93 - 8.06 (m. 2 H) 8.24 (d. J=2.0 Hz, 1 H) 8.47 (d, J=2.0 Hz, 1 H) 10.49 (s. 1 H) 12.28 - 12.42 (br, 1 H) MS (ESI/APCI Dual): 459 (M+1), 457 (M-1) 378 3-CF3-PH H 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.23 Cs. 6 H) 4.30 (s. 2 H) 6,89 (d, J=8.7 Hz, 1 H) 7.69 (d. J=8.7 Hz. 2 H) 7.76 - 7.93 (m_ 3 H) 7.95 - 8.06 (m, 2 H) 8.25 - 8.34 ( m, 2 H) 8.48 (d, J=2.0 Hz, 1 H) 10.57 Cs, 1 H) 12.31 - 12.41 (br, 1 H) MS (ESI/APCI Dual)·. 459 (M+1), 457 ( M-1) -293- 200918053 [Table 34] 379 3 - CF30 - Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.23 (s. 6 H) 4.29 (s, 2 H) 6.89 (d, J=8.7 Hz. 1 H) 7.60 - 7.73 (m. 4 H) 7.82 - 7.96 (m. 3 H) 7.98 - 8.08 (m, 2 H) 8.48 (d. J=1.9 Hz, 1 H) 10.48 (s 1 H) 12.29 -12.41 (br. 1 H) MS (ESI/APC1 Dual): 475 (M+1), 473 (M-1) Η RA RB 380 3-CF3〇-Ph H 1H NMR (300 MHz , DMSO-D6) δ ppm 1.80-2.15 (m, 4H) 2.31 -2.50 (m, 2H) 4.60 (s, 2H) 7.60 - 7.75 (m, 2H) 7.77 (d. J=8.9 Hz, 2H) 7.88 - 7.95 (m. 3H) S.04 (d. J=7.4 Hz. 1H) 8.95 (s, 2H) 10.52 (s, 1H) 12.48 (s, 1H) MS (ESI) : 48BCM+1) 486(M-1) 381 3-Me-4—F-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.83 - 2.13 (m, 4H) 2.33 (s. 3H) 2.25 - 2.45 (m. 2H) 4.59 (s, 2H) 7.31 (dd, J=8.9 Hz. 9.5 Hz. 1H) 7.74 (d, J=8.6 Hz. 2H) 7.82 - 8.96 (m, 4H) 8.93 (s. 2H 10.35 (s, 1H) 12.46 Cs. 1H) MS (ESI): 436 (M+1) 434 (M-1) 382 3-CI-4-Me-Ph H 1H NMR ¢300 MHz, DMSO-D6) Fippm ί.83 - 2.12 (m. 4H) 2.33 -2.45 (m. 2H) 2.42 (s, 3H) 4.59 (s. 2H) 7.54 (d. J=8.1 Hz, 1H) 7.75 (d. J=9.0 Hz 2H) 7.84 - 7.94 (m, 1H) 7.91 (d. J=9.0 Hz, 2H) 8.05 (s, 1H) 8.94 Cs. 2H) 10.42 (s, 1H) 11.39 - 13.45 (br, 1H) MS (ESI ): 452(M+1), 450CM-1) 383 3-CF3-4-C Ph Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.82 - 2.14 (m, 4 H) 2.32 -2.46 (m 2 H) 4.60 (s. 2 H) 7.73 - 7.82 (m, 2 H) 7.86 - 7.99 (m. 3 H) 8.25 - 8.33 (m, 1 H) 8.38 - 8.43 (m, 1 H) 8.95 (s 2 H) 10.65 (s. 1 H) 12.46 (s, 1 H) MS CESI/APCI Dual): 506 (M+1), 504 (M-1) 384 3-CF3-Ph H 1H NMR t300 MH z, DMSO-D6) &lt;5 ppm 1.80 - 2.11 Cm, 4H) 2.32 -2.45 (m, 2H) 4.58 (s, 2H) 7.76 (d, J=8.7 Hz. 2H) 7.75 - 7.83 (m. 1H) 7.90 (d, J= 8.7 Hz, 2H) 7.98 (d, J=7.8 Hz, 1H) 8.25 - 8.32 (m. 2H) 8.93 (s, 2H) 10.59 (s, 1H) 12.20 - 12.65 (br, 1H) MS(ESI): 472CM +0, 470(M-1) 385 3,4-diCI-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.83 - 2.14 (m, 4 H) 2.29 -2.47 (m. 2 H) 4.59 ( s. 2 H) 7.76 (d, J=8.9 Hz, 2 H) 7.81 - 7.94 (m, 3 H) 7.97 (dd, J=8.5, 2.1 Hz. 1 H) 8.25 (d, J=2.0 Hz, 1 H) 8.94 Cs, 2 H) 10.52 Cs, 1 H) 12.47 (s, 1 H) MS (ES1/APCI Dual): 472 (M+1), 470 (M-1) 386 3-CI-4-F -Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.80 - 2.14 Cm, 4 H) 2.32 -2.47 (m, 2 H) 4.59 (s. 2 H) 7.56 - 7.69 (m. 1 H) 7.76 ( d, J=8.7 Hz, 2 H) 7.90 (d, J=8.6 Hz, 2 H) 7.97 - 8.08 (m. 1 H) 8.23 (dd, J=7.2, 2.3 Hz, 1 H) 8.94 (s. 2 H) 10.48 (s, 1 H) 12.40 - 12.54 (br, 1 H) MS CESI/APCI Dual): 456 (M+1), 454 (M-1) 387 3,4-diMe-Ph H 1H NMR t300 MHz, DMSO-D6) &lt;5 ppm 1.82 - 2.15 (m, 4 H) 2.24 -2.47 (m, 2 H) 2.30 (s. 3 H) 2.33 (s. 3 H) 4.60 (s, 2 H) 7.30 (d. J=8.1 Hz, 1 H) 7.67 - 7.81 (m. 4 H) 7.87 - 7.97 (m, 2 H) 8.93 (s. 2 H) 10.26 (s, 1 H) 12.34 - 12.60 (br, 1 H) MS (ES1/ APCI Dual); 432 (M+1) °Y°&gt;BF RA RB 388 3-CF3 - Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.80 - 2.15 (m. 4 H) 2.34 -2.45 ( m, 2 H) 4.61 (s, 2 H) 7.59 - 7.88 (m, 4 H) 8 01 (d. J=8.4 Hz, 1 H) 8.23 - 8.38 (m, 2 H) 9.01 (s, 2 H) 10.51 (s, 1 H) 12.39 -12.55 {br, 1 H) MS (ESI/APCI Dual): 490 (M+1), 488 (M-1) -294- 200918053 [Table 1-35] RA RB 389 3,5-diMe-Ph H 1H NMR ¢300 MHz. DMSO-D6) 6 ppm 1.77 - 2.18 (m, 4 H) 2.23 -2.48 (m, 2 H) 2.36 (s. 6 H) 4.60 (s, 2 H) 7.16 - 7.31 (m. 1 H) 7.50 - 7.65 (m. 2 H) 7.66 - 7.81 (m, 2 H) 7.83 - 8.00 (m, 2 H) 8.93 Cs, 2 H) 10.30 (s, 1 H 12.22 - 12.67 (far, 1 H) MS iESI/APCl Dual): 430 (M-1) 390 〇&gt; H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.70 - 1.83 (m, 4 H) 1.85 -2.13 (m, 4 H) 2.26 - 2.46 (m. 2 H) 2.74 - 2.88 (m. 4 H) 4.59 (s. 2 H) 7.18 - 7.25 (m, 1 H) 7.66 - 7.78 (m, 4 H) 7.88 - 7.96 (m, 2 H) 8.93 Cs, 2 H) 10.25 (s, 1 H) 12.32 - 12.61 ( Br, 1 H) MS (ES1/APCI Dual): 458 (M+1), 456 (M-1) 391 3HPr-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.26 Cs. 3 H) 1.28 (s. 3 H) 1.80 - 2.14 (m. 4 H) 2.25 - 2.47 (m, 2 H) 2.92 - 3.08 (m. 1 H) 4.60 (s, 2 H) 7.41 - 7.53 (m. 2 H) 7.70 - 7.85 (m, 4 H) 7.87 - 7.97 (m, 2 H) 8.94 Cs, 2 H) 10.34 (s, 1 H) 12.26 - 12.68 Cbr, 1 H) MS (ESI/APCI Dual): 446 (M+ 1), 444 (M-1) 392 3-CI-4-Me〇-Ph H 1H NMR ¢300 MHz. DMSO-D6) δ ppm 1.79 - 2.15 Cm, 4 H) 2.31 -2.46 (m, 2 H) 3.96 (s, 3 H) 4.59 (s. 2 H) 7.32 (d, J=8.7 Hz, 1 H) 7.75 (d, J=8.7 Hz, 2 H) 7.90 (d, J=8.7 Hz. 2 H) 8.00 (dd, J=8.8. 2.3 Hz, 1 H) 8.11 (d, J=2.2 Hz, 1 H) 8.94 (s. 2 H) 10.31 (s, 1 H) 12.45 (s, 1 H) MS (ESI /APCI Dual): 468 CM+1), 466 (M-1) °V^&gt;B RA RB 393 3-CI-4-Me-Ph H 1H NMR (300 MHz. DMSOO6) 6 ppm 1.B1 - 2.15 (m, 4 H) 2.31 -2.45 (mt 5 H) 4.6t (s. 2 H) 7.37 - 8.10 (m. 6 H) 9.00 (s. 2 H) 10.29 (s, 1 H) 12.37 - 12.56 (br, 1 H) MS (ESI/APCI Dual): 470 (Μ+Ί), 468 (M~1) 〇丫. RA RB 394 3-CF3〇-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.00 - 1.13 (m, 2H) 1.18 -1.30 (m. 2H) 4.45 (s, 2H) 7.60 - 7.75 (m. 2H) 7.76 (d. J=8.6 Hz, 2H) 7.85 - 7.99 (m. 3H) 8.04 (d, J=8.0 Hz, 1H) 8.93 (d, J=0.9 Hz, 2H) 10.52 (s, 1H) 12.45 ( s, 1H) MS(ESI): 474(M+1) 472CM-1) 395 3—Me-4—F—Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.02 - 1.10 (m, 2H) 1.18 -1.27 (m, 2H) 2.33 (s, 3H) 4.45 (s, 2H) 7.32 (dd. J=9.0 Hz. 9.0 Hz. 1H) 7.74 (d, J=8.7 Hz, 2H) 7.83 - 8.97 (m , 4H) 8.93 (s, 2H) 10.36 Cs, 1H) 12.36 - 12.53 (br, 1H) MS(ESl): 422 (M+1) 420 (M-1) 396 3-Ch4-Me-Ph H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.04 - 1.09 Cm. 2H) 1.18 -1.25 (m. 2H) 2.42 (s. 3H) 4.45 (s, 2H) 7.54 (d, J=8.4 Hz. 1H) 7.75 (d , J=8.4 Hz, 2H) 7.84 - 7.94 (m, 1H) 7.91 (dt J=9.0 Hz, 2H) 8.05 Cs, 1H) 8.93 Cs. 2H) 10.42 (s. 1H) 11.75 - 13.09 (br. 1H) MSCESI): 438CM+1), 436(M-1) 397 3-CF3-4-C Ph Ph 1 H NMR (300 MHz. DMSO-D6) δ ppm 1.00 - 1.12 (m, 2 H) 1.17 -1.28 ( m. 2 H) 4.45 (s. 2 H) 7.71 - 7.83 (m. 2 H) 7.85 - 8.00 (m, 3 H) 8 .29 (dd, J=8.6, 1.2 Hz. 1 H) 8.41 (d, J=1.9 Hz, 1 H) 8.93 (s, 2 H) 10.65 (s, IH) V2.38 - 12.50 (br, i H MS (ESI/APCI Dual): 492 (M+1), 490 (M-1) 398 3-CF3-Ph H 1H NMR (300 MHz. DMSO-D6) fippm 1.03 - 1.09 (m, 2H) 1.19 - 1.25 (m. 2H) 4.45 (s. 2H) 7.76 (d, J=8.9 Hz, 2H) 7.76 - 7.85 (m. 1H) 7.91 (d. J=8.9 Hz, 2H) 7.98 (d, J=7.7 Hz , 1H) 8.25 - 8.34 (m, 2H) 8.93 Cs, 2H) 10.59 (s. 1H) 12.08 - 12.76 (br, 1H) MSCESI): 458(M+1). 456CM-1) -295- 200918053 [Table 1-36] 399 3,4-diCI-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.00 - M2 Cm. 2 H) 1.18 -1.28 (m, 2 H) 4.45 (s, 2 H) 7.70 - 7.81 (m, 2 H) 7.81 - 7.93 (m, 3 H) 7.97 (dd, J=8.4. 2.0 Hz, 1 H) 8.24 (d, J=2.0 Hz, 1 H) 8.93 (s, 2 H) 10.52 (s, 1 H) 12.27 - 12.63 (br, 1 H) MS (ESI/APCI Dual): 456 (M-1) 400 3-Ch4-F-Ph H 1H NMR (300 MHz, DMSO-D6) δ Ppm 1.00 - 1.12 Cm, 2 H) 1.18 -1.31 (m. 2 H) 4.45 (s, 2 H) 7.62 (t, J=8.9 Hz. 1 H) 7.70 - 7.81 (m. 2 H) 7.83 - 7.95 ( m, 2 H) 8.02 (ddd, J=8.7. 4.7, 2.3 Hz. 1 H) 8.23 (dd, J=7.1, 2.3 Hz. 1 H) 8.93 (st 2 H) 10.47 (st 1 H) 12.27 -12.62 Cbr, 1 H) MS (ESI/APCI Dual): 440 (M-1) 401 3,4-diMe-Ph H 1H NMR C300 MHz. DMSO-D6) δ ppm 1.01 - 1.10 Cm, 2 H) 1.18 -1.27 (m, 2 H) 2.31 (s, 3 H) 2.32 (s. 3 H) 4.45 (s, 2 H) 7.30 (d, J=7.9 Hz. 1 H) 7.65 - 7.82 (m. 4 H) 7.86 - 7.98 (m, 2 H) 8.92 (s, 2 H) 10.25(s, 1 H) 12.25 - 12.60 (far, 1 H) MS (ESI/APCI Dual): 416 (M -1) 402 3,5-diMe-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.00 - 1.11 (m, 2 H) 1.17 -1.29 (m. 2 H) 2.37 (s. 6 H) 4.45 (s, 2 H) 7.24 (s. 1 H) 7.58 (s. 2 H) 7.73 (d. J=8.7 Hz, 2 H) 7.91 (d, J=8.7 Hz. 2 H) 8.92 (s, 2 H 10.30 (s, 1 H) 12.39 - 12,50 (br, 1 H) MS (ESI/APCI Dual): 418 CM+1) 403 〇&gt; H 1H NMR C300 MHz, DMSO-D6) δ ppm 1.03 - T.10 (m, 2 H) 1.18 -1.26 (m. 2 H) 1.71 - 1.83 (m. 4 H) 2.73 - 2.88 (m, 4 H) 4.45 (s, 2 H) 7.17 - 7.24 (m, 1 H) 7.66 - 7.77 (m, 4 H) 7.87 - 7.95 (m, 2 H) 8.92 Cs, 2 H) 10.25 (s, 1 H) 12.26 - 12.65 (br, 1 H) MS (ESI/APCI Dual): 444 (M+U 442 (M-1) 404 3-iPr-Ph H 1H NMR (300 MHz, DMSO-06) δ ppm 1.04 - 1.10 (m. 2 H) 1.19 -1.25 (m, 2 H) 1.25 (s, 3 H) 1.28 (s. 3 H) 2.93 - 3.08 (m. 1 H) 4.45 (s, 2 H) 7.42 - 7.52 (m. 2 H) 7.71 - 7.85 (m, 4 H) 7.88 - 7.95 (m, 2 H) 8.93 (s, 2 H) 10,33 (s, 1 H) 12.27 - 12.64 (hr, 1 H) MS (ESI/APCI Dual) : 432 CM+1), 430 (M-1) 405 3-CI-4 - MeO-Ph H 1H NMR (300 MHz, DMSO-D6) &lt;5 ppm 1.02 - 1.11 Cm, 2 H) 1.17 -1.27 (m. 2 H) 3.96 (s, 3 H) 4.45 (s, 2 H) 7.31 {d. J=8.9 Hz, 1 H) 7.74 (d J=8.7 Hz. 2 H) 7.90 (d, J=8.9 Hz, 2 H) 8.00 (dd, J=8.7, 2.3 Hz, 1 H>8.11 (d, J=2.2 H2, 1 Η) B.92 (s, 2 H) 10.31 (s, 1 H) 12.35 -12.54 (br, 1 H) MS (ESI/APCI Dual): 454 CM+1), 452 (M-1) RA RB 406 3-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.61 - 1.76 (m. 6H) 1.96 -2.14 (m. 2H) 4.42 (s. 2H) 7.77 (d. J=8.4 Hz, 2H) 7.81 Cdd, J =7.8 Hz. 7.8 Hz, 1H) 7.92 (d. J=8.4 Hz. 2H) 7.99 (d, J=7.8 Hz, 1H) 8.24 -8.34 (m, 1H) 8.32 (s. 1H) 8.93 (s, 2H 10.61 (s. 1H) 12.25 -12.55 (br. 1H) MS (ESI): 486 (Μ+Ί) 484 (M-1) H RA RB 407 3-CF3-4-CI-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.25 (s, 6 H) 4.35 (s, 2 H) 7.74 - 7.81 (m. 2 H) 7.87 - 7.98 (m. 3 H) 8.29 (dd. J=8.4, 2.0 Hz 1 H) 8.42 (d, J=2.0 Hz. 1 H) 8.94 (s, 2 H) 10.66 (s, 1 H) 12.23 -12.63 (br, 1 H) MS (ESI/APCI Dual): 492 (M -1) 408 3,4-diCI-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.24 (s, 6 H) 4,35 (s, 2 H) 7.72 - 7.80 ( m, 2 H) 7.81 - 8.00 (m, 4 H) 8.24 (d. J=2.0 Hz. 1 H) 8.93 (s, 2 H) 10.53 (s. 1 H) 12.12 - 12.74 (br. 1 H) MS (ESI/APCI Dual): 458 (M-1) 409 3-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.25 (s. 6 H) 4.35 (s, 2 H) 7.73 - 7.85 ( m, 3 H) 7.88 - 7.95 (m. 2 H) 7.96 - 8.02 (m, 1 H) 8.26 - 8.35 (m. 2 H) 8.94 (s, 2 H) 10.61 (s. 1 H) 12.22 - 12.65 ( Br, 1 H) MS (ESI/APCI Dual): 460 CM+1). 458 (M-1) -296- 200918053 [Table 1-37] 410 3-CF3〇-Ph H 1H NMR (300 MHz, DMSO -D6) δ ppm 1.25 (s, 6 H) 4.35 (s, 2 H) 7.60 - 7.80 (m, 4 H) 7.87 - 7.96 (m, 3 H) 8.05 (dt J=7.7, 1.3 Hz. 1 H) 8.94 (s. 2 H) 10.52 (s, 1 H) 12.28 - 12.59 (br. 1 H) MS (ESl/APCI Dual): 476 (M+1), 474 (M-1) 411 3-C Bu 4 -Me-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.25 (s, 6 H) 2.42 (s, 3 H) 4.35 (s. 2 H) 7.51 - 7.57 (m, 1 H) 7.71 - 7.79 (m, 2 H) 7.85 - 7.95 (m. 3 H) 8.05 (d, J=1.9 Hz, 1 H) 8.93 (s. 2 H) 10.41 (s, 1 H) 12.14 -12.72 (br. 1 H) MS (ESI/APCI Dual): 440 (M+1). 438 (M-1) °Υ%Β rr°^b Η Η RA RB 412 2-CF3-4-CI-Ph H 1H NMR ¢300 MHz, DMSO-D6) (5ppm 1.80 - 2.15 Cm, 4H) 2.25 -2.45 (m. 2H) 4.54 (s, 2H) 6.88 (d, J=8.6 Hz, 1H) 7.56 (d. J= 8.9 Hz, 2H) 7.63 (d, J=8.3 Hz, 2H) 7.70 - 7.80 (m. 2H) 7.99 (dd, J=2.5 Hz, 8.8 Hz. 1H) 8.04 (d, J=8.6 Hz. 1H) 8.21 (s, 1H) 8.46 (d, J=2.4 Hz, 1H) 9.54 (s. 1H) 12.40 (s, 1H) MS (ESI): 520CM+1), 518CM-1) 413 3-Me-4-F ~Ph H 1H NMR (300 MHz, DMSO-D6) &lt;5 ppm 1.80 - 2.11 (m. 4 H) 2.22 (s. 3 H) 2.31 - 2.45 (m, 2 H) 4.53 (s. 2 H) 6.86 (d. J=8.6 Hz, 1 H) 7.05 ( t J=9.3 Hz, 1 H) 7.23 - 7.31 (m, 1 H) 7,37 (dd, J=7.0, 2.5 Hz, 1 H) 7.50 - 7.62 (m, 4 H) 7.97 (dd, J=8.7 2.6 Hz. 1 H) 8.44 (d, J=2.6 Hz, 1 H) 8.66 (s. 1 H) 8.78 (s, 1 H) 12.38 Cs, 1 H) MS CESI/APCI Dual): 450 CM+1 ), 448 (M-1) 414 2—Br - 5-Me-Ph H 1H NMR (300 MHz. DMSO-D6) tSppm 1.79 - 2.12 (m. 4 H) 2.28 (s. 3 H) 2.31 - 2.45 ( m, 2 H) 4.53 (s, 2 H) 6.81 (dd. J=8.2f 2.1 Hz, 1 H) 6.87 (d, J=8.6 Hz. 1 H) 7.48 (d. J=8.1 Hz, 1 H) 7.53 - 7.64 (m, 4 H) 7.93 (d, J=2.0 Hz. 1 H) 7.98 (dd. J=8.7, 2.6 Hz, 1 H) 8.12 (s. 1 H) 8.45 (d. J=2.6 Hz , 1 H) 9.58 (s, 1 H) 12.24- 12.53 (br, 1 H) MS (ESI/APCI Dual): 510 (M+1), 508 (M-1) 415 2-Ct-4-F- 5-Me-Ph H 1H NMR ¢300 MHz, DMSO-D6) 5ppm 1.82 - 2.10 (m, 4 H) 2.23 (d, J=1.9 Hz, 3 H) 2.31 - 2.45 (m, 2 H) 4.53 (sT 2 H) 6.87 (d, J=8.6 Hz, 1 H) 7.40 Cd J=9.2 Hz, 1 H) 7.52 - 7.64 (m, 4 H) 7.98 (dd, J=8.6, 2.6 Hz. 1 H) 8.02 ( d, J=8.1 Hz, 1 H) 8.27 (s, 1 H) 8.45 (d, J=2.2 Hz. 1 H) 9.43 (s. 1 H) 12.25 - 12.50 (br, 1 H) MS CESI/APCI Dual): 484 CM+1), 482 (M-1) 416 3-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.82 - 2.11 (m, 4H) 2.32 -2.44 (m, 2H) 4.54 (s, 2 H) 6.87 (d, J = 8.7 Hz 1 H) 7.32 (d, J=6.8 Hz, 1 H) 7.44 - 7.65 (m, 6 H) 7.98 (dd. J=8.6. 2.6 Hz, 1 H) 8.03 (s. 1 H) 8.45 (d, J=2.6 Hz, 1 H) 8.93 (s. 1 H) 9.10 (s. 1 H) 12.38 (s, 1 H) 417 3-CF3-4-CI-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.85 - 2.03 (m, 4 H) 2.32 -2.44 (m. 2H) 4.53 (s, 2 H) 6.87 (d, J=8.9 Hz, 1 H) 7.49 - 7.73 (m, 6 H) 7.98 (dd , J=8.6, 2.6 Hz, 1 H) 8.12 (d, J=2.2 Hz, 1 H) 8.45 Cd, J=2.6 Hz, 1 H) 8.99 Cs, 1 H) 9.22 (s, 1 H) 12.38 Cs, 1 H) 418 2 - F-5-Me-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.85 -2.03 Cm. 4 H) 2.28 (s. 3 H) 2.34 - 2.47 (m, 2 H) 4.53 (s, 2 H) 6.76 - 6.84 (m. 1 H) 6.87 (d, J=8.9 Hz. 1 H) 7.11 (dd, J=11.4. 8.3 Hz. 1 H) 7.45 - 7.67 (m, 4 H) 7.91 - 8.08 (m, 2 H) 8.40 - 8.62 (m, 2 H) 9.18 (s, 1 H) 12.38 Cs, 1 H) 419 2-C Bu 4-CF30-Ph H 1H NMR (300 MHz, DM SO-D6) 5ppm 1.71 -2.10 Cm, 4H) 2.30 -2.45 (m. 2H) 4.52 (s. 2H) 6.86 (d, J=8.7 Hz, 1H) 7.38 (d, J=9.3 Hz. 1H) 7.35 - 7.67 (m, 3H) 7.55 (d, J=9.0 Hz. 2H) 7.97 (dd, J=2.4 Hz. 8.7 Hz, 1H) 8.28 (d, J=9.3 Hz, 1H) 8.44 (d, J=2.4 Hz 1H) 8.47 (s. 1H) 9.56 (s. 1H) 12.27 - 12.49 (br. 1H) MS (ESI); 536CM+1), 534(M-1) 420 2-Me-4-CF3〇-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.80 - 2.18 (m, 4H) 2.28 (s, 3H) 2.30 - 2.43 (m, 2H) 4.52 (s. 2H) 6.86 (d. J=8.4 Hz, 1H) 7.16 (d. J=9.0 Hz, 1H) 7.22 (s, 1H) 7.54 (d. J=8.7 Hz. 2H) 7.59 (d. J=8.7 Hz, 2H) 7.92 - 7.99 (m, 2H) 8.07 (s, 1H) 8.43 (d. J=2.7 Hz. 1H) 9.19 (s, 1H) 12.39 (s, 1H) MSiESI): 516 (M+1) 514 (M-1) 421 2-F-5- CF3-Ph H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.80 - 2.15 Cm, 4H) 2.31 -2.50 (m, 2H) 4.55 (s, 2H) 6.89 (d, J=8.6 Hz. 1H) 7.37 - 7.45 (m, 1H) 7.47 - 7.55 (m. 1H) 7.57 (d. J=8.6 Hz. 2H) 7.64 (d. J=8.6 Hz, 2H) 7.99 (dd, J=2.5 Hz. 8.8 Hz, 1H) 8.46 (d, J=2.7 Hz. 1H) 8.60 -8.70 (m, 1H) 8.90 - 9.00 (m, 1H) 9.30 (s, 1H) 12.40 (s, 1H) MS(HSl): 504(MH). 50 2(M-1) -297- 200918053 [Table 1 - 3 8] 422 3-CI-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.79 - 2.15 Cm, 4H) 2.29 ~ 2.45 (m. 2H) 4.52 (s. 2H) 6.85 (d. J=8.7 Hz, 1H) 6.99 - 7.07 (m. 1H) 7.23 - 7.36 (m, 2H) 7.53 (d, J=8.7 Hz, 2H) 7.59 (d, J=8.7 Hz, 2H) 7.68 - 7.77 (m. 1H) 7.96 (dd, J=2.6 Hz, 8.6 Hz, 1H) 8.43 (d, J= 2.7 Hz, 1H) 8.86 (s, 1H) 6.90 (s, 1H) 12.30 - 12.49 (br, 1H) MS (ESI): 452 (M+1), 450CM-1) 423 3,5-diCI-Ph H 1H NMR (300 MHz. DMSO-D6) d ppm 1.75 - 2.09 Cm, 4H) 2.18 -2.44 (m. 2H) 4.52 (s, 2H) 6.86 (d, J=8.7 Hz. 1H) 7.14 - 7.18 (m, 1H) 7.48 - 7.63 (mt 4H) 7.60 (d, J= 8.7 Hz. 2H) 7.93 - 8.00 (m, 1H) 8.43 (s, 1H) 9.00 (s, 1H) 9.08 (s, 1H) 12.30 - 12.45 (br, 1H) MSCESI): 486CM+1), 484CM-1 424 3-C 卜 4-MeO-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.70 - 2.08 Cm, 4H) 2.20 -2.55 (m, 2H) 3.80 (s. 3H) 4.52 (s. 2H 6.85 (d, J=8.4 Hz, 1H) 7.08 (d, J=9.0 Hz, 1H) 7.27 (d, J=9.0 Hz, 1H) 7.53 (d. J=8.4 Hz, 2H) 7.58 (d, J =9.0 Hz, 2H) 7.66 (d, J=2.4 Hz, 1H) 7.96 (d. J=8.4 Hz. 1H) 8.43 (s, 1H) 8.6 7 Cs, 1H) 8.78 Cs, 1H) 12.38 (s. 1H) 425 2-Me-4-CN-Ph H 1H NMR ¢300 MHz, DMSO-D6) &lt;5 ppm 1.80 - 2.09 (m, 4H) 2.29 (s, 3H) 2.22 - 2.44 (m, 2H) 4.52 (s, 2H) 6.86 (d, J=8.7 Hz. 1H) 7.54 - 7.67 (m. 6H) 7.94 - 8.00 (m. tH) 8.22 - 8.30 (m, 2H) 8.44 (d, J=2.7 Hz, 1H) 9.23 (s. 1H) 12.32 - 12.46 (br, 1H) 426 2-F - 3-CI -Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.68 - 2.05 Cm. 4H) 2.22 -2.44 (m, 2H) 4.54 (s. 2H) 6.76 (d, J=8.6 Hz, 1H) 7.10 - 7.23 (m, 2H) 7.35 - 7.48 (m, 2H) 7.51 (d, J=8.0 Hz. 2H) 7.84 (d. J=8.6 Hz, 1H) 7.94 - 8.08 (m, 1H) 8.40 (d. J=2.4 Hz. 1H) 9.65 - 9.95 (br, 1H) 10.22 - 10.47 (br. 1H) MS (ESI): 470CM+1) 468(M-1) 427 4-t-Bu-Ph H 1H NMR C300 MHz, DMSO -D6) 6 ppm 1.27 (s, 9H) 1.70 - 2.10 (m, 4H) 2.20 - 2.55 (m. 2H) 4.53 (s. 2H) 6.87 (d, J=8.7 Hz. 1H) 7.30 (d. J= 8.4 Ηζ· 2H) 7.38 (d. J=9.0 Hz. 2H) 7.54 (d, J=8.4 Hz_ 2H) 7.59 (d, J=9.0 Hz, 2H) 7.97 (d, J=8.4 Hz, 1H) 8.44 ( s. 1H) 8.63 ¢5. 1H) 8.76 Cs. 1H) 12.32 - 12.48 (br, 1H) MS(ESI): 474 (M+1) 472 (M-1) 428 2-Me-5-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.80 - 2.10 Cm, 4H) 2.20 -2.50 (m. 2H) 2.33 (s, 3H) 4.52 (s, 2H) 6,86 (d. J=8.7 Hz. 1H) 7.27 (d. J=7.8 Hz, 1H) 7.41 (d, J=8.1 Hz, 1H) 7.56 (d, J=8.7 Hz. 2H) 7.61 (d. J=9.0 Hz, 2H) 7.97 (d, J=8.4 Hz. 1H) 8.24 (s. 1H) 8.38 (s, 1H) 8.44 Cs, 1H) 9.36 (s. 1H) 12.30- 12.48 (br, 1H) MSCESI): 500 (M+1) 498 (M-1) 429 3HPr-Ph H 1H NMR (300 MHz, DMSO-D6) 5 叩m U 9 (d_ J=6.9 Hz. 6H) 1.80 - 2.1 ϋ (m. 4H) - 2.55 (m. 2H) 2.84 (quint, J=6.8 Hz. 1H) 4.52 (s. 2H) 6.85 (d. J=8.7 Hz. 2H) 7.18 (dd. J=7.8 Hz. 7.8 Hz, 1H) 7.26 (d, J=9.3 Hz, 1H) 7.35 (s, 1H) 7.54 (d, J=9.6 Hz, 2H) 7.57 (d. J=9.3 Hz. 2H) 7.95 (dd, J=2.6 Hz. 8.9 Hz. 1H) 8.43 (d, J=2.1 Hz, 1H) 8.77 (s, 1H) 8.87[s, 1H) 12.25 - 12.54 (br, 1H) MSCESI): 460 (M+1) 458 (M-1) 430 3-MeO-4 - Cl-Ph H 1H NMR (300 MHz, DMSO-D6) &lt;5 叩m 1.80 - 2.07 (m. 4H) 2.25 -2.55 (m, 2H) 3.81 (s. 3H) 4.53 (s. 2H) 6.81 (d. J=8.4 Hz, 1H) 6.98 (d. J= 8.7 Hz. 1H) 7.26 (d. J=8.4 Hz. 1H) 7.40 - 7.58 (m, 5H) 7.91 (d. J=8.1 Hz. 1H) 8.41 (d. J=2.1 Hz, 1H) 9.88 - 10.00 ( Br. 1H) 10.00 - 10.12 (br, 1H) 11.80 - 12.90 (br. 1H) MSCES1): 482 (M+1) 480 (M-1) 431 H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.82 - 2.18 (m, 4H) 2.31 -2.47 (m, 2H) 4.54 (s, 2H) 6.88 (d. J=8.6 Hz, 1H) 7.11 (dd. J=2.2 Hz, 8.8 Hz, 1H) 7.34 (d. J =8.6 Hz. 1H) 7.55 (d, J=9.2 Hz. 2H) 7.61 (d. J=8.9 Hz, 2H) 7.69 (d. 2.1 Hz. 1H) 7.98 (dd. J=2.8 Hz. 8.5 Hz, 1H 8.45 (d, J=3.0 Hz, 1H) 8.88 (s, 1H) 8.96 (s, 1H) 12.39 (s, 1H) MStESl): 498CM+1), 496(M-1) 432 3-CF3-4 -Me-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.80 - 2.10 (m. 4H) 2.20 -2.43 (m, 2H) 2.37 (s, 3H) 4.52 (s. 2H) 6.86 (d. J=8.4 Hz. 1H) 7.33 (d, J=7.8 Hz, 1H) 7.45 - 7.62 Cm. 3H) 7.69 (d. J=8.7 Hz, 2H) 7.90 ~ 7.99 (m, 2H) 8.43 (s. 1H) 8.85 (s. 1H) 8.95 Cs. 1H) 12.31 - 12.45 (br, 1H) MSCESI): 500CM+1), 498(M-1) 433 2-CI-5-CF3 -Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.80 - 2.20 (m, 4H) 2.25 - 2.45 (m, 2H) 4.52 (s, 2H) 6.86 (d, J = 8.4 Hz. 1H) 7.37 (d J=9.9 Hz. 1H) 7.56 Cd, J=7.8 Hz, 2H) 7.62 (d, J=8.4 Hz. 2H) 7.72 (d. J=8.1 Hz, 1H) 7.98 (dd. J=1.4 Hz, 8.6 Hz. 1H) 8.45 (s. 1H) 8.64 (s, 2H) 9.67 (s, 1H) 12.31- 12.44 (br. 1H) MSCESI): 520CM+1), 518(ΜΊ) 434 3-CF3-4-CN -Ph H tH NMR ¢300 MHz. DMSO-D6) δ ppm 1.75 - 2.10 Cm, 4H) 2.20 -2.55 (m, 2H) 4.52 (s, 2H) 6.86 (d, J=8.7 Hz, 1H) 7.56 (d J=:8.7 Hz. 2H) 7.61 (d, J=9.0 Hz. 2H) 7.78 (d. J=9.0 Hz, 1H) 7.97 (dd. J=1.5 Hz, 8.7 Hz. 1H) 8.03 (d, J =8.1 Hz. 1H) 8.20 (s. 1H) 8.44 (d, J=2.1 Hz, 1H) 9.65 (s. 1H) 10.35 (s, 1H) 12.25 - 12.49 (br, 1H) MS(ESl): 511 ( M+1) 509 (M-1) 435 2-CI-4-F-Ph H 1H NMR (300 MHz. DMSO-D6) 5ppm 1.80 - 2.40 Cm, 6H) 4.52 (s, 2H) 6.86 (d, J =8.7 Hz, 1H) 7.17 - 7.26 (m, 1H) 7.48 (dd. J=3.0 Hz, 8.4 Hz. 1H) 7.54 (d, J=8.1 Hz, 2H) 7.60 (d, J=8.7 Hz, 2H) 7.97 (dd. J=2.4 Hz, 9.6 Hz, 1H) 8.11 (dd, J=6.0 Hz. 9.0 Hz. 1H) 8.33 (s. 1H) 8.44 Cd. J=2.4 Hz. 1H ) 9.44 ts. 1H) 12.33 - 12.41 (br. 1H) MSCESI); 470CM+1), 468CM-1) -298- 200918053 [Table 1-39] X VvV RA RB 436 2-CI-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) dppm 1.81 - 2.12 (m, 4H) 2.28 -2.45 (m, 2H) 4.54 (s, 2H) 6.87 (d. J=8.7 Hz. 1H) 7.22 (td, J 2.8 Hz, 8.6 Hz, 9.6 Hz 8.07 - 8.17 (m, 1H) MS (ESI): 488 (M+1), 486 (M-〇0 丫. , B j rr0^: RA RB 437 2-CM-F-Ph H 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.80 - 2.10 (m. 4H) 2.30 -2.45 (m, 2H) 4.54 (s. 2H 6.90 (d. J=8.6 Hz, 1H) 7.20 - 7.27 (m, 2H) 7.43 - 7.55 (m, 2H) 7.61 (dd. J=1.9 Hz, 13.6 Hz, 1H) 7.83 -7.90 (m, 1H) 8.10 (dd, J=5.7 Hz, 8.4 Hz. 1H) 8.32 (s, 1H) 8.40 (s. 1H) 9.63 (s. 1H) 12.39 (s. 1H) MS(ESI): 488(M+1) 486 (M-1) °Y°'RB 9- KH RA R巳438 2-CI-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) dppm 1.80 - 2.15 Cm. 4H) 2.30 -2.48 (m , 2H) 4.54 (s. 2H) 6.87 - 6.90 (mt 1H) 7.20 - 7.27 (m. 1H) 7.34 - 7.39 (m, 2H) 7.49 - 7.53 (m, 1H) 7.77 - 7.81 (m. 1H) 7.86 ( s. 1H) 8.07 - 8.13 (m, 1H) 8.20 - 8.21 (m, 1H) 8.40 (s. 1H) 9.62 Cs, 1H) 12.41 (s. 1H) MS(ESl): 504(M+1) 502CM- 1) V, day rnr^1 Η H RA RB 439 2-C Bu 4-F-Ph H 1H NMR ¢300 MHz. DMSO-D6) ippm 1.81 - 2.12 (m. 4H) 2.23 (s, 3H) 2.31 - 2.46 (m, 2H) 4.52 (s, 2H) 6.85 (d. J=8.6 Hz, 1H) 7.14 (d, J=8.0 Hz, 1H) 7.21 (td, J=3.0 Hz. 8.6 Hz. 1H) 7.37 ( d, J=8.6 Hz, 1H) 7.40 (s. 1H) 7.48 (dd, J=3.0 Hz. 8. 6 Hz. 1H) 7.69 (dd. J= 2.1 Hz. 8.6 Hz. 1H) 8.11 (d. J=2.7 Hz. 1H) 8.08 - 8.16 (m. 1H) 8.32 Cs. 1H) 9.37 (s. 1H) 12.10 - 12.80 (br. 1H) MS (ESI): 484 (M+1). 482 (M-1) rr^ Η H RA RB 440 2-F-5-CI-Ph H 1H NMR C300 MHz, DMSO-D6 δ ppm 1.80 - 2.15 (m, 4H) 2.30 -2.45 (m, 2H) 4.54 (s, 2H) 6.87 (d, J=8.7 Hz, 1H) 7.04 - 7.09 (m, 1H) 7.25 - 7.40 (m. 1H) 7.55 (d. J=8.7 Hz, 2H) 7.62 (d. J=8.7 Hz, 2H) 7.95 - 8.00 (m. 1H) 8.27 - 8.32 (m. 1H) 8.45 (d. J=1.5 Hz. 1H 8.79 (s, 1H) 9.25 (s, 1H) 12.30 - 12.45 (br, 1HJ MS (ESI): 470 (M+1). 468CM-1) 441 2-C Bu 5-F-Ph H 1H NMR ( 300 MHz. DMSO-D6) 6 ppm 1.80 - 2.15 (m, 4H) 2.30 -2.45 (m. 2H) 4.54 (s. 2H) 6.85 - 6.95 (m. 1H) 6.87 (d. J=8.6 Hz, 1H) 7.49 - 7.55 (m, 1H) 7.56 (d, J=8.9 Hz, 2H) 7.63 (d. J=8.6 Hz. 2H) 7.98 (dd, J: 2 7 Hz, 8.7 Hz, 1H) 8.12 (dd. J =3.2 Hz, U.9 Hz, 1H) 8.45 (d, J=2.7 Hz. 1H) 8.51 (s. 1H). 9.65 - 9.72 (br. 1H) 12.30 -12.45 (br, 1H) MSCESI): 470 ( M+1), 468(M-1) -299- 200918053 [表卜40] 〇Υ%Β F RA RB 442 2-GI-5-F-Ph H 1HNMR (300 MHz, DMSO-D6) (5 ppm 1.81 -2.11 (m, 4H) 2.30-2.44 (m, 2H) 4.54 (s, 2H) 6.88 (d. J=8.4 Hz, 1H) 6.87 - 6.96 (m 1H) 7.46 - 7.56 (m. 2H) 7.65 (dd, J=1.8 Hz, 12.9 Hz, 1H) 8.04 (dd, J=2.6 Hz, 8.6 Hz, 1H) 8.11 (dd, J=2.9 Hz. 11.9 Hz , 1H) 8.24 (t, J=8.7 Hz. 1H) 8.51 (d. J=2.4 Hz, 1H) 8.99 (s, 1H) 9.59 (s, 1H) 11.85 - 13.01 (br. 1H) MS (ESI): 488 CM+1), 486 (M-1) 443 2-F_5-CF3-Ph H 1H NMR C300 MHz, DMSO-D6) 5ppm 1.81 - 2.10 Cm, 4H) 2.31 -2.47 (m, 2H) 4.54 (s, 2H) 6.88 (d, J=8.7 Hz. 1H) 7.37 - 7.45 (m, 1H) 7.47 - 7.56 (m, 2H) 7.65 (dd, J=1.8 Hz, 12.9 Hz, 1H) 8,04 (dd, J =2.4 Hz. 8.7 Hz, 1H) 8.26 (t. J=8.9 Hz, tH) 8.51 (d. J=2.7 Hz. 1H) 8.65 (dd. J=2.4 Hz, 7.2 Hz. 1H) 9.26 (d, J =2.1 Hz, 1H) 9.40 (d, J=2.7 Hz, 1H) 11.80 - 13.06 (br, 1H) MSCESI): 522 (M+1). 520 (M-1) 444 2-F—5-Me - Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.82 - 2.10 (m, 4H) 2.28 (s. 3H) 2.32 - 2.44 (m, 2H) 4.54 (s. 2H) 6.77 - 6.85 (m, 1H 6.B8 (d, J=8.7 Hz, 1H) 7.12 (dd, J=8.4 Hz. 11.4 Hz, 1H) 7.49 (d, J=8,7 Hz, tH) 7.6 3 (dd. J=2.0 Hz. 12.8 Hz. 1H) 7.98 - 8.07 (m, 2H) 8.27 (t, J=8.6 Hz, 1H) 8.50 (d, J=2.1 Hz, 1H) 9.00 (s, 1H) 9.12 (s, 1H) 11.62 - 12.95 (br, 1H) MSCESI): 468 (M+1), 466 (M-1) °Y%B j 〇Η H RA RB 445 2-CI-5-F-Ph H 1H MMR (300 MHz, DMSO-D6) (5 叩〇 1.76-2.12 (yang, 4^〇2.30-2.50 (m, 2H) 4.54 (s, 2H) 6.87 - 6.97 (m, 2H) 7.23 (dd, J=1.8 Hz. 8.3 Hz, 1H) 7.46 - 7.58 (m, 2H) 7.61 (dd, J=1.6 Hz, 13.5 Hz. 1H) 7.84 - 7.90 (mt tH) 8.10 (dd, J=3.0 Hz, 11.6 Hz , 1H) 8.32 (s, 1H) 8.55 (s. 1H) 9.84 (s, 1H) 12.34 - 12.41 (br, 1H) MSCESI): 488 (M+1), 486 (M-1) 446 2-F- 5-CF3-Ph H 1H NMR (300 MHz, DMSO-D6) &lt;5 叩m 1.80- 2.11 (m, 4H) 2.30 -2.46 (m. 2H) 4.54 (s. 2H) 6.90 (d. J=8.7 Hz, 1H) 7.24 (dd. J=2.0 Hz. 8.3 Hz, 1H) 7.38 - 7.57 (m, 3H) 7.62 (dd. J=2.1 Hz, 13.2 Hz. 1H) 7 R7 (ri, J=8 7 Hr. 1H) 8.33 (s, 1H) 8.60 (dd. J~2.4 Hz. 7.2 Hz, 1H) 8.99 (d, J=2.7 Hz. 1H) 9.47 (s. 1H) 12.39 (s, 1H) MS(ESl): 522 (M+1), 520 (M 1) w Γ Γ Ά 0 Η Η RA RB 447 2-CI-5-F-Ph H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.82 - 2.15 (τη, 4H) 2.34 -2.47 (m. 2H) 4.55 (s, 2H) 6.87 - 6.98 (m. 1H) 6.88 (d, J=3.9 Hz. 1H) 7.33 - 7.45 (m, 2H) 7.54 (dd. J=6.1 Hz. 9.1 Hz, 1H) 7.80 (dd. J=2.4 Hz, 8.6 Hz, 1H) 7.89 (d. J=1.8 Hz. 1H) 8.11 (dd, J=3.0 Hz, Π.6 Hz, 1H) 8.21 (d, J=2.4 Hz, 1H) 8.57 (s. 1H) 9.83 ( s, 1H) 12.33 -12.48 (br/ 1H) MS (ESI): 504 (M+1). 502 (M-1) 448 2-F-5-CF3-Ph H 1H NMR (300 MHz, DMSO-D6 ) t5ppm 1.80-2.14 (m, 4HJ 2.27 -2.45 (m, 2H) 4,54 (s, 2H) 6.89 (d, J=8.0 Hz, 1H) 7.28 - 7.52 (m, 4H) 7.79 (dd, J= 2.4 Hz, 8.6 Hz, 1H) 7.81 (s. 1H) 8.21 (d, J=2.4 Hz. 1H) 8.55 - 8.63 (m, 1H) 8.98 (d, J=2.1 Hz. 1H) 9 .44 (s. 1H) 12.37 -12.41 (br. 1H) MS (ESI): 538 (M+1). 536 (M-1) °γ\β -vV〇^ RA R巳449 3 - Me-Ph H 1H NMR (300 MHz, DMSO-D6) 6 ppm Ί .80 - 2.11 (m, 4 H) 2.28 (s. 3 H) 2.32 - 2.44 (m, 2 H) 4.53 (s. 2 H) 6.76 - 6.92 (m, 2 H) 7.10 - 7.28 (m, 2 H) 7.31 (s. 1 H) 7.51 - 7.63 (m. 4 H) 7.97 (dd, J=8.6. 2.6 Hz. 1 H) 8.44 (d. J =2.5 Hz. 1 H) 8.63 (s, 1 H) 8.78 (s, 1 H) 12.37 (s, 1 H) MS CES1/APCI Dual): 432 (M+1). 430 (M-1) 450 3 —CF30-Ph H 1H NMR (300 MHz. DMSO-D6) (5ppm 1.79 - 2.12 (m, 4 H) 2.31 -2.43 (m. 2 H) 4.53 (s, 2 H) 6.87 (d, J^9.0 Hz 1 H) 6.91 - 7.00 (m, 1 H) 7.26 - 7.35 (m. 1 H) 7.36 - 7.45 (m, 1 H) 7.51 - 7.64 (m, 4 H) 7.67 - 7.74 (m, 1 H) 7.97 (dd, J=8.6, 2.6 Hz, 1 H) 8.44 (d, J=3.1 Hz, 1 H) 8.89 Cs. 1 H) 9.04 Cs, 1 H) 12.37 (s, 1 H) MS (ESl/APCl Duat ): 502 (M+1), 500 (M-1) -300- 200918053 [Table 1-41] 451 2,5-diCI-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.78 - 2.28 ( m, 4H) 2.30 -2.50 (m, 2H) 4.53 (s, 2H) 6.87 (d. J=8.4 Hz. 1H) 7.05 - 7.20 (m. \H) 7.5t (d, J=8.6 H z. 1H) 7.56 (d, J=S.6 Hz, 2H) 7.63 (d, J=8.6 Hz. 2H) 7.99 (dd. J=2.4 Hz. 8.7 Hz. 1H) 8.35 (d, J=2.1 Hz , 1H) 8.46 (d, J=2.7 Hz, 1H) 8.50 ($, 1H), 9.60 - 9.70 (br, 1H) 12.35 -12.45 (br. 1H) MSCESI): 486(M+1). 484(M -1) %-, o Η M RA RB 452 2-CF3-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) tSppm 1.00 - 1.10 (m, 2H) 1.16 -1.25 (mt 2H) 4.39 ( s. 2H) 6.90 (d, J=9.2 Hz, 1H) 7.55 (d, J=8.6 Hz. 2H) 7.50 - 7.65 (m, 2H) 7.61 (d, J=8.6 Hz, 2H) 7,92 (dd , J=5.2 Hz, 8.8 Hz, 1H) 7.98 (dd. J=2.7 Hz, 8.3 Hz. 1H) 8.14 (s, 1H) 8.43 (d. J=2.4 Hz, 1H) 9.40 (s, 1H) 12.39 ( s, 1H) MS(ESI): 490CM+1), 488CM-1) 453 2-CF3-4-C mp Ph H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.00 - 1.10 (m, 2H) 1.15 - 1.25 (m, 2H) 4.40 (s, 2H) 6.90 (d. J=8.6 Hz. 1H) 7.56 (d, J=8.3 Hz. 2H) 7.62 (d. J=8.6 Hz. 2H) 7.70 - 7.79 (m , 2H) 7.94 - 8,03 (m, 1H) 8.03 (d, J=8.0 Hz. 1H) 8.21 (s, 1H) 8.40 - 8.45 (m. 1H) 9.54 (s, 1H) 12.39 (s. 1H) MS (ESI): 506CM+1), 504CM-1) 454 2-CI-4-CF3-Ph H ΪΗ NMR (300 MHz. DMSO-D6) ¢5ppm 1.00 - 1.10 Cm, 2H) 1.15 -1.25 (m. 2H) 4.40 (s. 2H) 6.91 (d, J=8.9 Hz, 1H) 7.58 (d. J=8.9 Hz, 2H) 7.64 (d. J=8.6 Hz. 2H) 7.71 (d, J=8.9 Hz. 1H) 7.90 (s, 1H) 7.95 -8.03 (m. 1H) 8.40 - 8.45 (m. 1H) 8.50 (d, J=8.9 Hz. 1H) 8.68 (s, 1H) 9.74 (s, 1H) 12.39 Cs. 1H) MS (ESI): 506CM+1), 504 (M-1) 455 3 - CF3-4-F-Ph H 1H NMR ¢300 MHz, DMSO-D6) (5 ppm 1.00 - 1.10 (m, 2H) 1.15 -1.25 (m, 2H) 4.40 (s, 2H) 6.90 (d. J=8.6 Hz, 1H) 7.46 (t, J=9.8 Hz. 1H) 7.56 (d. J=8.3 Hz, 2H) 7.61 (d. J=8.9 Hz. 2H) 7.52 - 7.70 (m. 1H) 7.90 - 8.05 (m. 2H) 8.43 (d. J=2.1 Hz. 1H) 8.94 (s. 1H) 9.08 Cs, 1H 12.39 (s, 1H) MS (ESI &gt;. 490CM+1), 488 (M-1) 456 2-CF3〇-Ph H 1H NMR C300 MHz. DMSO-D6) ¢5 ppm 0.96 - 1.06 (m, 2H) ) 1.14 -t.25 (m, 2H) 4.38 (s. 2H) 6.89 (d. J=8.6 Hz, 1H) 7.10 (dd. J=7.4 Hz, 8.3 Hz. 1H) 7.35 (dd, J=7.4 Hz) 7.7 Hz. 1H) 7.38 (d, J=8.9 Hz, 1H) 7.55 (d, J=8.6 Hz. 2H) 7.61 (d. J=8.9 Hz, 2H) 7.97 (dd, J=2.5 Hz. 8.5 Hz , 1H) 8.28 (dT J=8.0 Hz. 1H) 8.42 (d, J=2.4 Hz. 1H) 8.51 (s. 1H) 9.39 (s, 1H) 12.38 (s, 1H) MS(ESl): 488 (M +1) 486 C M-1) 457 3-CI-4-F-Ph H 1H NMR C300 MHz, OMSO-D6) &lt;5 ppm Q.98 - 1.06 (m, 2H) 1.14 -1.26 (m. 2H) 4.38 (s, 2H) 6.88 (d, J = 8.6 Hz. TH) 7.25 - 7.38 (m, 2H) 7.53 (d J=8.9 Hz, 2H) 7.58 (d. J=8.6 Hz, 2H) 7.81 (d. J=7.7 Hz. 1H) 7,96 (d, J=8.6 Hz, tH) 8.41 (s, 1H) 8.93 (s· 1H) 8,96 (s. 1H) 12.37 (s, 1H) MSCESI): 456 (M+1) 454 (M-1) 458 2-CI-4-CF3〇-Ph H 1H NMR (300 (M, 2H) 1.16 7.53 - 7.65 (m. 1H) 7.56 (d. J=9.0 Hz, 2H) 7.62 Cd. J=8.7 Hz. 2H) 7.97 (dd. J=8.7 Hz. 2.4 Hz, 1H) 8.29 (d. J= 9.0 Hz. 1H) 8.42 (d, J=2.4 Hz. 1H) 8.48 Cs, 1H) 9.56 Cs. 1H) 12.26 - 12.54 (br, 1H) MSCESI): 522CM+1), 520CM-1) 459 2-Me -4-CF3〇-Ph H 1H NMR (300 MHz, DMSO-D6) dppm 0.99 - 1.06 Cm, 2H) 1.14 -1.24 (m. 2H) 2.28 (s, 3H) 4.37 (s, 2H) 6.88 (d, J=8.4 Hz. 1H) 7.16 (d, J=9.0 Hz. 1H) 7.21 (st 1H) 7.54 (d. J=9.0 Hz, 2H) 7.59 (d, J=8.7 Hz. 2H) 7.96 (d, J =9.0 Hz. 2H) 8.09 (s, 1H) 8.40 (d, J=2.4 Hz, 1H) 9.21 Cs, 1H) 11.98 - Ϊ2.72 (br, 1H) MSCESI): 502(M+1). 500CM- 1 460 3-CF30-Ph H 1H NMR (300 MHz, DMSO-D6) dppm 1.01 - 1.07 (m. 2H) 1.15 -1.24 (m, 2H) 4.38 (s. 2H) 6.89 (d, J = 9.0 Hz, 1H) 6.95 (d. J=7.8 Hz. 1H) 7.31 (d. J=9.3 Hz, 1H) 7.41 (t. J=8.3 Hz. 1H) 7.55 (d, J=9.0 Hz. 2H) 7.60 (d, J=9.0 Hz, 2H) 7.70 (s. 1H) 7.97 (dd. J= 2.3 Hz, 8.6 Hz, 1H) 8.42 (d, J=2.1 Hz, 1H) 8.90 (s. 1H) 9.06 (s. ΊΗ) 12.25 -12.52 Cbr, 1H) MSCESI): 488CM+1), 486(M-1) 461 cycloHexyt H 1H NMR ¢300 MHz, DMSO-D6) ¢5 ppm 1.03 (qt J=3.5 Hz. 2H) 1.08 - 1.40 (mt 7H) 1.48 - 1.59 (m. 1H) 1.60 - 1.72 (m, 2H) 1.75 -1.86 (m, 2H) 3 40 - 3 52 (m, 1H) 4.37 (s, 2H) 6.10 (d, J= 7.5 Hz. 1H) 6.87 (d. J=8.7 Hz. 1H) 7.45 (d, J=8.4 Hz, 2H) 7.52 (d, J=8.7 Hz, 2H) 7.93 (dd, J=2.6 Hz, 8.6 Hz, 1H) 8.38 (d, J=2.7 Hz, 1H) 8.40 (s, 1H) 12.38 (s, 1H) MSiESI). 410 (M+1) 408 (Μ-Ί) 462 2-F-5-〇F3~ Ph H 1H NMR ¢ 300 MHz, DMSO-D6) 5 ppm 1.06 (dd. J=3.9 Hz. 6.6 Hz, 2H) 1.22 (dd, J=4.0 Hz, 7.0 Hz, 2H) 4.40 (s. 2H) 6.91 (d , J=8.6 Hz, 1H) 7.36 - 7.45 (m. 1H) 7.47 - 7.54 (m, 1H) 7.57 (d, J=8.6 H^. 2H) 7.6 3 (d. J=8.9 Hz, 2H) 7.99 (dd. J=2.7 Hz. 8.9 Hz. 1H) 8.43 (d, J=2.4 Hz. 1H) 8.60 - 8.68 (m, 1H) 8.94 (d. J= 3.0 Hz, 1H) 9.30 (s, 1H) 12.40 (s, 1H) MS(ESl): 49Q(M+t), 488(M-〇-301 - 200918053 [Table 1-42] 463 4-CF3〇- Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 0.95 - 1.14 Cm. 2H) 1.Π -1.21 (m. 2H) 4.39 (s. 2H) 6.87 (d, J=8.0 Hz, 1H) 7.28 ( d, J=8.0 Hz, 1H) 7.46 - 7.62 (m, 7H) 7.95 (d, J=8.2 Hz. 1H) 8.40 (s. 1H) 9.05 - 9.30 (br, 2H) 12.00 - 12.30 (br, 1H) MSCES1): 488 (M+1) 486 (M-1) 丫, * Η Η RA RB 464 2,4-diMe-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.60 - 1.75 (m. 6H) 1.96 -2.13 (m, 2H) 2.21 (s, 3H) 2.23 (s, 3H) 4.34 (s, 2H) 6.84 (d. J=9.2 Hz, 1H) 6.95 (d. J= 8.6 Hz. 1H) 6.99 ( s, 1H) 7.53 (d. J=9.2 Hz, 2H) 7.57 (d, J=8.9 Hz. 2H) 7.66 (d. J=8.3 Hz, 1H) 7.87 (s, 1H) 7.95 (dd. J=2.4 Hz. 8.6 Hz, 1H) 8.41 (d, J=2.4 Hz. 1H) 9.04 (s. 1H) 12.27 -12.34 (br, 1H) MSCESI): 460(M+1), 458(M-1) 465 2 -CI-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.60 - 1.75 Cm, 6H) 1.95 -2.12 (m, 2H) 4.35 ( s, 2H) 6.86 (d, J=8.7 Hz. 1H) 7.23 (ddd, J=2.9 Hz. 8.1 Hz, 8.9 Hz, 1H) 7.49 (dd, J=2.7 Hz, 8.4 Hz, 1H) 7.55 (d, J=8.1 Hz. 2H) 7.61 (d, J=8.4 H2, 2H) 7.97 (dd, J= 2.4 Hz. 8.7 Hz, 1H) 8.12 (d, J=5.9 H2, 9.2 Hz, 1H) 8.33 (s, 1H) 8.43 (d, J=2.4 Hz. 1H) 9.45 (s, 1H) 12.31 (s, 1H) MSCESI): 484 (M+1) 482 (M-1) 466 2-F_5-Me - Ph H 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.60 - 1.74 Cm, 6H) 1.98 -2.12 (m, 2H) 2.28 (s. 3H) 4.35 (s, 2H) 6.76 - 7.85 (m. 1H) 6.86 (d, J=8.7 Hz, 1H) 7.11 (dd. J=8.1 Hz. 11.4 Hz, 1H) 7.54 (d, J=8.7 Hz. 2H) 7.60 (d, J=9.0 Hz, 2H) 7.93 - 8.03 (m, 2H) 8.43 (d. J=2.4 Hz, 1H) 8.51 (d, J=2.4 Hz, 1H) 9.17 (s, 1H) 12.31 (s, 1H) MS(ESI): 464 (M+1) 462 CM-1 ) 〇#. ΗH RA RB 467 2,4-diMe-Ph H 1H NMR (300 MHz. DMSO-D6) 5ppm 1.20 - 1.61 im, 8H) 1.91 -2.06 (m, 2H) 2.20 (s, 3H) 2.22 (s, 3H) 4.30 (s. 2H) 6.82 (d, J=8.7 Hz. 1H) 6.95 (d. J=8.7 Hz, 1H) 6.98 (s, 1H) 7.50 - 7.60 (m, 4H) 7.65 (d. J= 7.8 Hz. 1H) 7.87 (s, 1H) 7.95 (dd, J=2.6 Hz, 8.6 Hz. 1H) 8.40 (d. J=2.7 Hz. 1H) 9.02 - 9.06 (br. 1H) 12.30 - i2.36 ( Br, iH) MSCESI): 474CM+1) 468 2-CM-F-Ph H 1H NMR (300 MHz, DMSO-D6) 6 ppm 1.20 - 1.63 (m, 8H) 1.91 -2.05 (m. 2H) 4.30 ( s. 2H) 6.82 (d. J=8.4 Hz, 1H) 7.21 (td. J=2.8 Hz. 8.7 Hz. 1H) 7.48 (dd. J= 3.0 Hz, B.7 Hz. 1H) 7.53 (d, J = 9.0 Hz. 2H) 7.59 (d, J=9.0 Hz, 2H) 7.95 (dd. J=2.7 Hz. 8.7 Hz. 1H) 8.11 (dd, J=6.0 Hz, 9.3 Hz, 1H) 8.32 (s, 1H) 8.41 (d. J=2.7 Hz, 1H) 9.43 Cs, 1H) 12.28 - 12.37 (br. 1H) MS(ESI): 498(M+1) RA RB 469 2—C Bu 4-F-5-Me -Ph H IH NMR (300 MHz. DMSO-D6) 5 ppm 1.83 - 2.15 (m. 4H) 2.25 (s, 3H) 2.33 - 2.50 (m, 2H) 4.60 (s. 2H) 7.42 (d. J=9.5 Hz , 1H) 7.59 (d. J=8.9 Hz. 2H) 7.69 (d, J=8.6 Hz, 2H) 8.02 (d. J=8.3 Hz, 1H) 8.30 ¢5, 1H) 8.91 (s, 2H) 9.48 Cs, 1H) 12.33 - 12.60 (br, 1H) MSCESI): 485(M+1)t 483(M-1) 470 2-CM-F- Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.84 - 2.19 Cm, 4H) 2.30 -2.50 (m. 2H) 4.60 (s. 2H) 7.17 - 7.29 (m, 1H) 7.50 (dd. J=2.7 Hz B.6 Hz. 1H) 7.59 (d. J=8_6 Hz, 2H) 7.70 (d, J=8.6 Hz, 2H) 8.13 (dd, J=5_7 Hz. 9.5 Hz· IH) B.36 (s, 1H) B.9Us, 2H) 9.50 (s, 1H) 12.32 -12.59 (br, 1H) MS (ESI): 47KM+1), 469(M-1) 471 3-CI-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) ippm 1.85 - 2.15 (m, 4H) 2.32 -2.48 (m. 2H) 4.60 (s, 2H) 7.30 - 7.40 (m. 2H) 7.59 (d. J=9.2 Hz. 2H 7.69 (d. J=8.9 Hz, 2H) 7.80 - 7.85 (m. 1H) 8.91 (s, 2H) 8.95 Cs, 2H) 12.47 (s, 1H) MSCESI): 47KM+1), 469 (M-1) 472 3-CI-Ph H 1H NMR (300 MHz. DMSO-D6) 5ppm 1.84 - 2.11 (m, 4H) 2.31 -2.46 (m, 2H) 4.58 (s, 2H) 7.00 - 7.50 (m, 1H) 7.42 - 7.35 (mt 2H) 7.58 (d, J=8.7 Hz. 2H) 7.67 (d. J=8.7 Hz, 2H) 7.71 (s, IH) 8.89 (s. 2H) 8.93 (s, 1H) 8.95 (s, 1H) 12.20 - 12.65 (br, 1H) MS (ESI): 453 (M+1). 45KM-1) -302- 200918053 [Table 1-43] 473 2~F-5-Me-P h H 1H NMR ¢ 300 MHz, DMSO-D6) dppm 1.85 - 2.16 Cm, 4H) 2.28 (s. 3H) 2.36 - 2.47 (m, 2H) 4.59 (s. 2H) 6.78 - 6.85 (m. 1H) 7.12 ( Dd, J=8.3 Hz. 11.3 Hz, 1H) 7.58 (d, J=8.7 Hz, 2H) 7.68 (d. J=8.7 Hz. 2H) 7.99 (d. J=7.5 Hz. 1H) 8.53 (s, 1H 8.90 (s, 2H) 9.23 (s, 1H) 12.26 - 12.70 (hr, 1H) MS (ESI): 451CM+1), 449 (M-1) 474 2-F-3-CI-Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.82 - 2.15 Cm, 4H) 2.30-2.45 (m, 2H) 4.59 (s, 2H) 7.14 - 7.24 (m. 2H) 7.58 (d, J=8.1 Hz, 2H 7.69 (dt J=8.7 Hz, 2H) 8.07 - 8.16 (m. 1H) 8.77 (d. J=2.4 Hz, 1H) 8.90 (s, 2H) 9.29 (s. 1H) 12.28 - 12.64 (br. 1H) MS (ESI): 47KM+1), 469 (M-1) 475 3-CF3-4-Me-Ph H 1H NMR ¢ 300 MHz, DMSO-D6) δ ppm 1.81 - 2.11 (m, 4H) 2.30 -2.46 (m. 2H) 2.38 (s, 3H) 4.59 (s. 2H) 7.35 (d. J=8.1 Hz, 1H) 7.52 (d, J=8.1 Hz, 1H) 7.59 (d, J=8.4 Hz, 2H) 7.67 (d, J=7.8 Hz, 2H) 7.94 (s. 1H) 8.90 (s. 2H) 8.93 (s. 1H) 8.99 (s, 1H) 12.30 - 12.63 (br. 1H) MS(ESI): 501CM+ 1), 499(M-1) 476 3-CF3-4-F-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.83 - 2.17 Cm, 4H) 2.25 -2.50 ( m. 2H) 4.60 (s, 2H) 7.46 (t, J=9.8 Hz, 1H) 7.60 (d, J=8.6 Hz, 2H) 7.63 - 7.73 (m. 1H) 7.69 (d. J=8.9 Hz, 2H 8.02 (dd. J=2.5 Hz, 6.4 Hz, 1H) 8.91 (s, 2H) 9.0t (st 1H) 9.11 (s, 1H) 12.43 - 12.52 (br, 1H) MSCESI): 505CM+1), 503 (M-1) 477 3_Me〇-4-CI-Ph H 1H NMR (300 MHz, DMSO-D6) &lt;5 叩阳1.85-2.16(阳,4^2.32-2.48 (m. 2H) 3.85 Cs, 3H) 4.60 (s, 2H) 6.98 (dd. J=2.5 Hz, 8.5 Hz, 1H) 7.31 (d. J=8.6 Hz. 1H) 7.43 (d, J=2.1 Hz, 1H) 7.59 (d, J=8.3 Hz. 2H) 7.68 (d, J=8.6 Hz, 2H) 8.85 - 9.02 (m, 4H) 12.43 - 12.53 (br, 1H) MS (ESI): 483 (M+1), 48KM-1) 478 3-CI-4-Me〇-Ph H 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.82 - 2.15 Cm , 4H) 2.30 -2.50 (m, 2H) 3.81 (s. 3H) 4.59 (s, 2H) 7.09 (d. J=8.9 Hz. 1H) 7.28 (dd, J=2.7 Hz. 8.6Hz 1H) 7.57 (d , J=8.6 Hz, 2H) 7.62 - 7.70 (m, 3H) 8.72 - 8.81 (br, 1H) 8.85 - 8.95 (br. 1H) 8.89 (s, 2H) 12.39 - 12.46 (br. 1H) MS (ESI&gt; 483(M+1) 48KM-1) 479 3-iPr-Ph H 1H NMR (300 MHz, DMSO-D6) ά 叩m 1.20 (d_ J=6.9 Hz, 6H) 1.80 - 2.15 (m. 4H) 2.30 - 2.50 (m. 2H) 2.85 (q. J=6.8 Hz, 1H) 4.58 (s. 2H) 6.87 (d. J=7.4 Hz, 1H) 7.20 (t, J=7.7 Hz. 1H) 7.27 (d, J=8.3 Hz. 1H) 7.35 (s. 1H) 7.58 (d, J=8.9 Hz. 2H) 7.66 (d, J=8.9 Hz, 2H) 8.67 (s. 1H) 8.87 (s, 1H) 8.81 - 8.92 Cm, 2H) 12.46 (s. 1H) MS (ESI): 461 (M+1) 459CM-1) 480 2-CF3-4-F-Ph H 1H NMR (300 MHz, DMS -L)b) ό ppm 1.80 - 2.12 (m. 4H) 2.30 - 2.50 (m. 2H) 4.58 (s, 2H) 7.51 - 7.64 (m, 2H) 7.58 (d. J=8.6 Hz. 2H) 7.79 ( d, J = 8.9 Hz, 2H) 7.91 (dd. J = 5.1 Hz · 9.2 Hz, 1H) 8.15 (s, 1H) 8.90 Cs, 2H) 9.43 (s, 1H) 12.46 (s. 1H) MS (ESI) : 505(M+1) 503CM-1) 481 2-F-5-CF3-Ph H 1H NMR ¢300 MHz, DMSO-D6) fippm 1.84 - 2.17 (m, 4H) 2.32 -2.47 (m. 2H) 4.60 (s, 2H) 7.37 - 7.57 (m, 2H) 7.60 (d, J=8.6 Hz. 2H) 7.71 (d, J=8.9 Hz. 2H) 8.60 - 8.68 (m, 1H) 8.92 (s, 2H) 8.97 (s, 1H) 9.36 (s. 1H) 12.41 - 12.5^ (br, 1H) MS (ESI): 505 (M+1), 503 (M-1) 482 2-Me-5-CF3-Ph H 1H NMR C300 MHz, DMSO-D6) dppm 1.81 - 2.15 (m, 4H) 2.19 -2.50 (mT 2H) 2.37 (s, 3H) 4.59 (s, 2H) 7.29 (d. J=8.3 Hz, 1H) 7.42 (d , J=7.7 Hz 1H) 7.60 (d, J=8.6 Hz, 2H) 7.69 (d. J=9.2 Hz. 2H) 8.22 (s. 1H) 8.38 (s. 1H) 8.90 (s. 2H) 9.36 (s , 1H) 12.46 (s. 1H) MSCESI): 50KM+1) 499(M-1) 483 2-CI-5-F-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.85 - 2.14 (m , 4H) 2.32 ~ 2.47 (mT 2H) 4.60 (s. 2H) 6.92 (ddd. J=3.1 Hz. 8.0 Hz, 8.9 Hz, 1H) 7.53 (dd, J=6.1 Hz, 9.1 Hz, 1H) 7.60 (d. J=8.6 Hz, 2H) 7.71 (d, J=8.6 Hz. 2H) 8.12 (dd, J=3.3 Hz. 11.9 Hz. 1H) 8.56 (s. 1H) 8.91 (st 2H ) 9.74 (s, 1H) 12.40 - 12.55 (br, 1H) MS (ESI): 471 (M+1), 469 (M-1) 丫, B o it -L! ^ iT Y F RA RB 484 2 -CI-4-F-Ph H 1H NMR (300 MHz: DMSO-卩6) dppm 1.8G - 2.13 (m, 4 H) 2.30 -2.48 (m. 2 H) 4.59 (s, 2 H) 7.23 (ddd , J=9.1. 8.3, 3.1 Hz. 1 H) 7.49 (dd, J=8.6, 3.0 Hz. 1 H) 7.53 - 7.62 (m, 1 H) 7.75 (dd, J=12.8, 2.0 Hz. 1 H) 8.12 (dd, J=9.2, 5.8 Hz. 1 H) 8.27 (t J=8.6 Hz. 1 H) 8.83 (s, 1 H) 8.95 (s. 2 H) 9_36 - 9.48 (m, 1 H) 12.21 - 12.70 (br, 1 H) MS (ES1/APCI Dual): 489 (M+1), 487 (M-1) -303- 200918053 [Table 44] 485 2_CI-5-F-Ph H 1H NMR (300 MHz, DMSO-D6) fippm 1.82 - 2.14 (m, 4 H) 2.31 -2.48 (m. 2 H) 4.59 (s, 2 H) 6.93 (ddd. J=8.8, 7.8. 3.1 Hz. 1 H) 7.52 ( Dd. J=8.9. 6.0 Hz. 1 H) 7.59 (dd, J=8.6, 1.8 Hz, 1 H) 7.76 (dd, J=12.8, 2.0 Hz, 1 H) 8.11 (dd, J=11.8, 3.1 Hz . 1 H) 8.28 (t. J=8.6 Hr, 1 H) 8.96 (s. 2 H) 8.97 - 9.05 (m. 1 H) 9.60 - 9.68 (m, 1 H) 12.33 - 12. 59 Cm. 1 H) MS (ESI/APCI Dual): 489 CM+1), 487 (M-1) 486 2-F-5-CF3-Ph H 1H NMR (300 MHz. DMSO-D6) dppm 1.81 - 2.14 Cm, 4 H) 2.29 -2.48 (m. 2 H) 4.59 (s, 2 H) 7.37 - 7.46 (m, 1 H) 7.47 - 7.63 (m. 2 H) 7.76 (dd, J=12.7. 2.1 Hz 1 H) 8.30 (t. J=8.6 Hz. 1 H) 8.65 (dd. J=7.3, 2.0 Hz, 1 H) 8.96 (s, 2 H) 9.27 - 9.34 (m, 1 H) 9.39 -9.46 ( m. 1 H) 12.31 - 12.62 (br, 1 H) MS (ESI/APCI Dual): 523 (M+1). 521 (M-1) 487 2-F-5-Me~Ph H 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.81 - 2.14 Cm. 4 H) 2.30 (s, 3 H) 2.31 - 2.47 (m, 2 H) 4.59 (s, 2 H) 6.79 - 6.87 (m, 1 H) 7.12 (dd. J=11.4, 8.3 Hz, 1 H) 7.57 (dd. J=8.6. 1.7 Hz, 1 H) 7.74 (dd, J=12.8, 2.0 Hz, 1 H) 8.02 (dd. J=7.9, 2.0 Hz. 1 H) 8.27 - 8.35 (m. 1 H) 8.95 (s, 2 H) 8.99 - 9.07 (m, 1 H) 9.13 - 9.22 (m. 1 H) 12.29 - 12.61 (br. 1 H) MS ( ESI/APCI Dual): 469 (M+1). 467 (M-1) °γ%0 Η H RA RB 488 3-CF3〇-Ph H 1H NMR (300 MHz, DMSO-D6) 5ppm 1.80 - 2.14 Cm , 4 H) 2.31 -2.46 (m, 2 H) 4.59 (s, 2 H) 6.95 (d, J = 10.1 Hz, 1 H) 7.26 - 7.36 (m. 1 H) 7.36 - 7. 46 (m, 1 H) 7.54 - 7.64 (m. 2 H) 7.64 - 7.73 (m. 3 H) 8.90 (s, 2 H) 8.95 (s, 1 H) 9.07 (s, 1 H) 12.33 - 12.50 ( Br MS (ESI/APCI Dual): 503 (M+1), 501 (M-1) rvo4 ο ;Γ^γΛ^Ν Μ H RA RB 489 4-CF30-Ph H 1H NMR (300 MHz, DMSO-D6 ) &lt;5 ppm 0.99 - 1.11 (m, 2H) 1.16 -1.28 (m, 2H) 4.45 (s. 2H) 7.29 (d. J=8.3 Hz, 2H) 7.58 (d. J-8.1 Hz. 4H) 7.66 ( d. J=8.7 Hz. 2H) 8.88 (s, 2H) 8.94 - 9.24 (m, 2H) 12.44 Cs. 1H) MSCESI): 489(M+1), 487(M-1) 490 3 - MeO_4-Cl -Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.01 - 1.10 (m, 2 H) 1.16 -1.27 (m, 2 H) 3.84 (s, 3 H) 4.44 (s. 2 H) 6.92 - 7.02 (m. 1 H) 7.30 (d, J=8.7 Hz. 1 H) 7.42 (s, 1 H) 7.54 - 7.62 (m, 2 H) 7.62 -7.70 Cm. 2 H) 8.83 - 8.97 (m. 4 H 12.34 - 12.46 (br. 1 H) MS (ESI/APCI Dual): 469 CM+1), 467 (M-1) 491 3-CI-Ph H 1H NMR ¢300 MHz. DMSO-D6) 6 ppm 1.03 - 1.09 (m. 2 H) 1.19 -1.25 (m. 2 H) 4.44 (s. 2 H) 7.03 (dt, J=6,6. 2.2 Hz, 1 H) 7.25 -7.35 (m, 2 H) 7.55 - 7.61 (m, 2 H) 7.64 - 7.74 (m, 3 H) 8.89 (s. 2 H) 8.95 (s, 1 H) 8.97 (s, 1 H) 12.43 (s. 1 H) MS (ESI/APCI Dual): 437 (M-1) 492 3-CI-4-Me〇-Ph H 1H NMR (300 MHz, DMSO-D6) ¢5 ppm 1.03 - 1.09 Cm, 2 H) 1.19 -1.25 (m, 2 H ) 3.82 (s, 3 H) 4.44 (s, 2 H) 7.09 (d, J=9.0 Hz. 1 H) 7.28 (dd. J=8.9, 2.6 Hz. 1 H) 7.54 - 7.60 (m. 2 H) 7.62 - 7.69 (m, 3 H) 8.71 (s, 1 H) 8.85 Cs, 1 Η) 8.8B (s, 2 H) 12.43 (s, 1 H) MS (ESI/APCI Dual): 469 (M+ 1) 493 3-C Bu 4-F-Ph H 1H NMR (300 MHz. DMSO-D6) δ ppm 1.02 - 1.09 (m, 2 H) 1.18 -1.26 (m, 2 H) 4,44 (s, 2 H) 7.29 - 7.39 (m, 2 H) 7.54 - 7.61 (m, 2 H) 7.63 - 7.70 (m, 2 H) 7.78 - 7.85 (m, 1 H) 8.89 (s. 2 H) 8.95 (s. 2 H) 12.44(5, 1 H) MS (ESI/APCI Dual): 455 (M-1) 494 2-F-5-Me_Ph H 1H NMR (300 MHz. DMSO -D6) δ Dpm 1.03 - 1.10 (m, 2 H) 1.18 -1.25 (m, 2 H) 2.28 (s, 3 H) 4.44 (s. 2 H) 6.77 - 6.85 (m, 1 H) 7.11 (dd. J=11.4. 8.4 Hz, 1 H) 7.53 -7.61 (mT 2 H) 7.64-7.71 (m. 2 H) 7.96 - 8.02 (m, 1 H) 8.50 - 8.56 (m, 1 H) 8.89 (s. 2 H) 9.22 (s, 1 H) 12.27 - 12.58 (br, 1 H) MS (ESI/APCI Dual): 437 (M+1), 435 (M-1) 495 3-CF3-4-F-Ph H 1H NMR (300 MHz. DMSO-D6) δ Ppm 0.99 - 1.10 Cm, 2 H) 1.16 -1.28 (m, 2 H) 4.45 (s, 2 H) 7.39 - 7.49 (m, 1 H) 7.54 - 7.62 (m, 2 H) 7.62 - 7.71 (m, 3 H) 8.02 (dd, J-5.6, 2.2 Hz, 1 H) 8.88 (s, 2 H) 9.01 - 9.31 (m, 2 H) 12.35 - 12.50 (br, 1 H) MS (ESI/APCI Dua l); 491 (M+1), 489 (M-1) -304- 200918053 [Table 45] 496 2-CF3-4-F-Ph H 1H NMR C300 MHz, DMSO-D6) d ppm 0.99 - 1.10 (m, 2 H) 1.17 -1.27 (m. 2 H) 4.44 (s, 2 H) 7.50 - 7.73 (m, 6 H) 7.90 (dd. J=8.9. 5.4 Hz. 1 H) 8.16 - 8.25 (br , 1 H) 8.88 (s. 2 H) 9.43 - 9.53 (br, 1 H) 12.28 - 12.55 (br, 1 H) MS CESI/APCI Dual): 491 (M+1), 489 (M-1) 497 2-F-5-CF3-Ph H 1H NMR ¢300 MHz, DMSO-D6) δ ppm 0.98- 1.11 (m, 2 H) 1.11 -1.31 (m. 2 H) 4.45 (s, 2 H) 7.34 - 7.45 (m. 1 H) 7.45 - 7.55 (m. 1 H) 7.55 - 7.64 (m. 2 H) 7.64 - 7.73 (m. 2 H) 8.62 (d. J=7.2 Hz, 1 H) 8.90 (s. 2 H) 8.97 - 9.10 (br. 1 H) 9.37 - 9.50 (br. 1 H) 12.31 -12.54 (br, 1 H) MS (ESI/APCI Dual): 489 (M-1) 498 3_CF30-Ph H 1H NMR (300 MHz, DMSO-D6) dppm 1.01 - 1.10 (m, 2H) 1.18 -1.26 (m, 2H) 4.44 (s, 2H) 6.95 (d, J=8.0 Hz. 1H) 7.31 (d. J=9.2 Hz 1H) 7.40 (t, J=8.2 Hz, 1H) 7.57 (d. J=8.9 Hz, 2H) 7.66 (d. J=8.6 Hz. 2H) 7.70 (s, 1H) 8.88 (s, 2H) 8.93 - 9.02 (br. ΊΗ) 9.05 - 9.18 (br, 1H) 12.20 - 12.67 (br. 1H) MSCESI): 489(M+1) 499 2-Me-4 -CF3〇-Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.03 - 1.12 (m, 2H) 1.20 -1.27 (m, 2H) 2.31 (s, 3H) 4.45 (s. 2H) 7.18 (d, J=8.6 Hz, 1H) 7.24 (s, 1H) 7.59 (d, J=8.9 Hz. 2H) 7.68 (d, J=8.3 Hz, 2H) 7.97 (d, J=9.2 Hz, 1H) 8.12 (s, 1H) 8.90 Cs. 2H) 9.26 (s, 1H) 12.45 (s, 1H) MS (ESI): 503 (M+1) 501 (M-1) 500 2-C 丨-4-CF30 - Ph H 1H NMR (300 MHz, DMSO-D6) δ ppm 1.03 - 1.09 Cm, 2H) 1.18 -1.25 (m. 2H) 4.44 (s, 2H) 7.39 (d, J=8.7 Hz. 1H) 7.59 (d. J=9.0 Hz 2H) 7.63 (d. J=2.4 Hz, 1H) 7.69 Cd, J=8.7 Hz. 2H) 8.29 (d, J=9.3 Hz, IH) 8.52 (s. 1H) 8.89 (s. 2H) 9.63 (s , 1H) 12.35 - 12.55 Cbr. 1H) MS (ESI): 523 (M+1) 521 (M-1) 501 2-CF30-Ph H 1H NMR (300 MHz. DMSO-D6) dppm 0.89 - 1.10 Cm, 2H) U0 -1.28 (m. 2H) 4.42 (s. 2H) 7.09 (t. J=7.6 Hz. 1H) 7.24- 7.42 (m, 2H) 7.57 (d. J=8.6 Hz, 2H) 7.67 (d, J=8.6 Hz, 2H) 8.25 (d. J=8.0 Hz, IH) 8.54 Cs. 1H) 8.87 (s. 2H) 9.45 (s. 1H) 11.59 - 13.20 (br, 1H) MS(ESI): 489( Μ+ΐ), 487(M-1) 502 2-CI-4-F-PH H MSCES1): 457CM+1), 455(M-1) RA RB 503 2-CI-4-F-Ph H 1H NMR (300 MHz, DMS0-D6) dppm 1.57 - 1.80 (m, 6H) 1.97 -2.15 (m, 2H) 4.40 (s. 2H) 7.22 (td, J=3.1 Hz. 8.6 Hz. 1H) 7.49 (dd , J=3.1 Hz, 8.2 Hz, 1H) 7.58 (d. J=8.6 Hz, 2H) 7.67 (d. J=8.6 Hz, 2H) 8.11 (dd, J=5.7 Hz. 8.8 Hz. 1H) 8.37 - 8.45 (br, 1H) 8.88 Cs. 2HJ 9.52 - 9.60 (br, 1H) 12.36 - 12.42 (br. 1H) MS(ESI): 485(M+1) 483(M-1) 504 2 - F—5-Me —Ph H 1H NMR (300 MHz, DMS0-D6) δ ppm 1.60 - 1.79 (m, 6H) 1.97 -2.13 (m, 2H) 2.28 (s. 3H) 4.40 (s, 2H) 6.77 - 6.85 (m, 1H 7.11 (dd, J=8.3 Hz. 11.3 Hz. 1H) 7.57 (d, J=8.4 Hz. 2H) 7.67 (d. J=8.4 Hz. 2H) 7.99 (d. J=8.1 Hz, 1H) 8.52 ( d, J=2.7 Hz, 1H) 8.89 (s, 2H) 9.21 (s, 1H) 12.38 (s, 1H) MS(ESl): 465 (M+1) 463 (M-1) V0'* RA RB 505 2-C 卜 4-F-Ph H IH NMR (300 MHz, DMS0-D6) δ ppm 1.70 - 1.95 tm, 2H) 1.97 -2.13 (m, 2H) 2.t7 - 2.32 (m, 2H) 3.73 (d J=6.3 Hz, 2H) 7.12 (t, J=6.0 Hz. 1H) 7.22 (td, J=3.1 Hz. 8.6 Hz. 1H) 7.48 (dd. J=3.2 Hz, 8.9 Hz. IH) 7.47 - 7.56 (m, 2H) 7.57 (d, J=8.4 Hz, 2H) 8.12 (td, J^5.9 Hz. 9.2 Hz. 1H) 8.31 (s, IH) 8. 59 (s. 2H) 9.41 (s. 1H) 12.26 (ε. 1H) MS (ESI): 470 (M+1). 468 (M-1) °Y%BH RA RB 506 3-F-4-ChPh Na 1H NMR (300 MHz, DMS0-D6) δ ppm 1.70 - 1.95 (m, 4 H) 2.23 -2.38 (m. 2 H) 4.42 (s, 2 H) 6.81 (d. J=8.7 Hz, 1 H) 7.53 - 7.61 (m, 2 H) 7.76 (t. J=7.9 Hz. 1 H) 7.85 - 8.02 (m, 4 H) 8.17 (dd. J=10.3. 1.9 Hz. 1 H) 8.42 (d, J= 2.5 Hz, 1 H) 11.01 - 11.20 (br, 1 H) MS (ESI/APCI Dual): 453 (M-1) -305- 200918053 [Table 1-46] °Υ%Β RA RB 507 3-iPr- Ph Na 1H NMR (300 MHz, DMSO-D6) δ ppm 1.26 (s, 3 H) 1.28 (s, 3 H) 1.71 - 1.97 (m, 4 H) 2.23 - 2.39 (m. 2 H) 3.00 (m, 1 H) 4.47 (s, 2 H) 7.41 - 7.51 (m, 2 H) 7.67 - 7.74 (m, 2 H) 7.81 - 7.97 (m, 4 H) 8.89 (s. 2 H) 10.57 (s, 1 H MS (ESI/APCI Dual): 444 (M-1) D丫〇, RB 0 Η H RA RB 508 2-CF3-4-C Ph Ph Na 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.72 - 1.95 (m. 4H) 2.25 -2.42 (mt 2H) 4.57 (s, 2H) 6.63 (d, J=8.3 Hz. 1H) 7.15 (d, J=8.0 Hz. 2H) 7.38 (d. J=8.6 Hz. 2H 7.62 - 7.80 (m, 4H) 8.34 (d, J=2.4 Hz. 1H) 10.39 - 10.71 Cbr. 1H) 1 1.33 - 11.63 (br, 1H) 509 3-Me-4-F-Ph Na 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.83 - 1.99 (m, 4 H) 2.22 (d. J = 1.4 Hz, 3 H 2.39 - 2.49 (m. 2 H) 4.64 (s. 2 H) 6.55 (d. J=8.6 Hz, 1 H) 7.0t (t. J=9.3 Hz. 1 H) 7.07 (d. J=8.7 Hz) , 2 H) 7.35 (d, J=8.7 Hz, 2 H) 7.38 - 7.46 (m, 1 H) 7.56 (dd· J=8.6. 2.6 Hz, 1 H) 7.61 (dd, J=7.2. 2.4 Hz, 1 H) 8.35 (d, J=2.6 Hz, 1 H) 11.38 (s, 1 H) 11.41 (s, 1 H) MS (ESI/APCI Dual): 450 (M+1), 448 (M-1) 510 2-Br-5-Me-Ph Na 1H NMR (300 MHz, DMSO-D6) 5 ppm 1.72 - 1.96 (m, 4 H) 2.28 (s. 3 H) 2.30 - 2.42 (m, 2 H) 4.50 (s , 2 H) 6.71 (d, J=8.7 Hz. 1 H) 6.82 (dd, J=8.3, 1.8 Hz. 1 H) 7.30 (d. J=8.7 Hz. 2 H) 7.45 (d, J=8.1 Hz , 1 H) 7.49 (d. J=8.7 Hz, 2 H) 7.71 (d, J=1.9 Hz, 1 H) 7.78 (dd, J=8.6. 2.6 Hz, 1 H) 8.35 (d, J=2.5 Hz . t H) 9.62 (s, 1 H) 11.03 (s, 1 H) MS (ESI/APCI Dual): 510 (M+1), 508 (M-1) 511 2-CI_4-F-5_Me_Ph Na 1H NMR (300 MHz, DMSO-D6) ¢5 ppm 1.71 - 2.02 (m, 4 H) 2.22 (d. J=1.7 Hz. 3 H) 2.28 - 2.44 (m. 2 H) 4.53 (s. 2 H) 6.68 ( d. J=8.6 Hz, 1 H) 7.20 - 7.29 (m , 2 H) 7.33 (d, J=9.3 Hz, 1 H) 7.42 - 7.49 (m. 2 H) 7.68 - 7.79 (m, 2 H) 8.34 (d. J=2.6 Hz. 1 H) 10 09 (s 1 H) 11-18 (s, 1 H) MS (ESI/APCI Dual): 484 (M+1), 482 (M-1) 512 3-CF3-Ph Na 1H NMR (300 MHz, DMSO-D6) 5ppm 1.85 - 2.03 Cm.. 4 H) 2.31 - 2.41 (m. 2 H) 4.68 (s. 2 H) 6.52 (d, J=8.7 Hz, 1 H) 7.04 (d, J=9.0 Hz, 2 H) 7.21 (d, J=7.6 Hz, 1 H) 7.30 (d, J=8.7 Hz, 2 H) 7.41 -7.57 (m. 2 H) 7.82 (d, J=9.2 Hz, 1 H) 8.23 (s. 1 H) 8.36 (d, J=2.6 Hz. 1 H) 11.74 Cs, 1 H) 12.16 Cs. 1 H) MS (ESI/APCI Dual): 486 CM+1) 513 3-CF3-4 - Cl-Ph Na 1H NMR ¢300 MHz, DMSO-D6) 6 ppm 1.87 - 2.01 Cm, 4 H) 2.30 -2.44 (m. 2H) 4.67 (s. 2 H) 6.55 (d. J=8.6 Hz. t H) 7.09 (d J=8.6 Hz. 2 H) 7.32 (d, J=8.7 Hz, 2 H) 7.47 - 7.65 (m, 2 H) 7.85 (dd, J 8.7. 2.5 Hz, 1 H) 8.37 (s. 2 H 11.85 (s. 1 H) 12.45 (s, 1 H) MS (ESl/APGI Duat): 520 (M+U 518 (M-1) 514 2-F-5-Me-Ph Na 1H NMR (300 MHz , DMSO-D6J (5 ppm 1.71 - 1.96 Cm, 4 H) 2.28 (s. 3 H) 2.30 - 2.44 (m, 2 H) 4.55 (s, 2 H) 6.59 (d, J=8.6 Hz, 1 H) 6.74 - 6.86 (m, 1 H) 6.9 6 - 7.20 (m, 3 H) 7.39 (d, J=8.9 Hz, 2 H) 7.63 Cdd. J=8.2. 2.3 Hz, 1 H) 7.68 - 7.76 (m, 1 H) 8.32 (d, J-2.6 Hz. 1 H) 10.46 Cs, 1 H) 11.15 (s, 1 H) MS (ESI/APCI Dual): 450 (M+1) 515 3-Me-Ph Na 1H NMR ¢300 MHz, DMSO-D6) δ Ppm 1.84 - 2.03 (m., 4 H) 2.31 - 2.41 (m. 2 H) 4.64 (s. 2 H) 6.51 (d, J=9.0 Hz, 1 H) 6.71 (d, J=7.3 Hz. 1 H ) 7.01 (d, J=8.7 Hz, 2 H) 7.12 (d, J=7.9 Hz, 1 H) 7.32 (d, J=8.7 Hz. 2 H) 7.41 (d, J=8.1 Hz. 1 H) 7.48 - 7.57 (m. 2 H) 8.30 - 8.36 (m, 1 H) 11.74 (s. 1 H) 12.16 (s. 1 H) MS (ESI/APCI Dual): 432 (M+1) 516 2-CI- 4-CF30-Ph Na 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.72 - 1.97 (m, 4H) 2.30 -2.46 (m. 2H) 4.53 (s, 2H) 6.68 (d, J=8.7 Hz, 1H 7.23 (d, J=8.7 Hz, 2H) 7.31 - 7.38 (m. 1H) 7.45 (d. J=8.7 Hz. 2H) 7.55 (d. J=2.7 Hz. 1H) 7 73 (dd. J=1.7 Hz, 8.6 Hz, 1H) 8.04 (d. J=9.0 Hz, 1H) 8.33 (d, J=2.7 Hz. 1H) 10.30 - 10.41 (br 1H) 11 30 - 11.38 (br. 1H) 517 2-Me- 4-CF3〇-Ph Na 1H NMR ¢300 MHz, DMSO-D6) δ ppm 1.75-1.95 (m, 4H) 2.30 -2.45 (m. 2H) 2.36 (s. 3H) 4.58 (s, 2H) 6.60 (d, J=8.6 Hz, 1H) 7.05 -7.18 (m. 4H) 7.36 (d. J=8.0 Hz. 2H) 7.62 (dd, J=2.5 Hz, 8.5 Hz. 1H) 7.76 (dt J=8.9 Hz , 1H) 8.31 (d, J=2.7 Hz, 1H) 10.50 (s, 1H) 11.32 Cs. 1H) -306- 200918053 [Table 1-47] 518 2-F-5-CF3-Ph Na 1H NMR ¢300 MHz. DMSO-D6) δ ppm 1.74 - 2.00 (m. 4H) 2.32 -2.48 (m, 2H) 4.60 (s, 2H) 6.53 (d, J=8.6 Hz, 1H) 7.05 (d. J=8.6 Hz, 2H) 7.38 (d, J=8.6 Hz, 2H) 7.32 - 7.50 (m, 2H) 7.57 (dd, J=2.5 Hz, 8.6 Hz, 1H) 8.32 (d. J=2.4 Hz. 1H) 8.44 (dd. J=1.8 Hz, 7.2 Hz, 1H) 11.36 - 11.51 Cbr, 1H) 11.60 - 1 1.78 (br, 1H) 519 2,5-diCI-Ph Na 1H NMR C300 MHz. DMSO-D6) δ ppm 1.70 - 1.92 Cm , 4H) 2.27 -2.42 (m, 2H) 4.52 (s. 2H) 6.67 (d, J=8.4 Hz, 1H) 7.08 (dd, J=2.4 Hz. 8.7 Hz. 1H) 7.15 - 7.30 (m, 2H) 7.38 - 7.53 (m, 3H) 7.74 (d, J=9.0 Hz. 1H) 8.14 (dd. J=2.4 Hz. 6.6 Hz, 1H) 8.33 (d. J=2.1 Hz, 1H) 10.15 - 10.30 (br, 1H) 11.30- 11.45 (br, 1H) 520 3-CI-Ph Na 1H NMR (300 MHz, DMSO-D6) 5ppm 1.82 - 2.00 (m, 4H) 2.36 -2.52 (m. 2H) 4.66 (s, 2H) 6.51 (d. J=8.6 Hz. 1H) 6.91 (d, J=7.7 Hz. 1H) 7.02 (d, J=8.0 Hz, 2H) 7.22 - 7.34 (m, 3H) 7.45 - 7.58 (m, 2H) 7.87 (s, 1H) 8.35 (s, 1H) 11.62 - 11.70 (br, 1H) 11.87 - t1. 96 (br, 1H) 521 3t5-diCI-Ph Na 1H NMR (300 MHz, DMSO-D6) dppm 1.83 - 2.03 Cm, 4H) 2.33 -2.58 (m, 2H) 4.67 (s, 2H) 6.51 (d. J =8.3 Hz, 1H) 6.99 - 7.09 (m. 3H) 7.27 (d, J=8.6 Hz, 2H) 7.51 (d, J=8.3 Hz, 1H) 7.75 (d. J=2.1 Hz, 2H) 8.36 (s , 1H) 11,72 - H.84 (br, 1H) 12.27 - 12.35 (br. 1H) 522 3-CI-4-Me〇-Ph Na 1H NMR (300 MHz, DMSO-D6) dppm 1.85 - 2.01 Cm , 4H) 2.37 -2.52 (m. 2H) 3.80 (s. 3H) 4.64 (s. 2H) 6.53 (d. J=8.6 Hz. 1H) 7.01 -7.09 (m, 3H) 7.30 (d. J=8.6 Hz , 2H) 7.51 (dd, J=2.4 Hz, 8.9 Hz, 1H) 7.53 (dd, J=2.5 Hz, 9.4 Hz. 1H) 7.83 (d, J=2.4 Hz. 1H) 8.34 (d, J=2.7 Hz , 1H) 11.40 - 11.45 (br, 1H) 11.53 - 11.60 (br. 1H) 523 2-Me-4-CN-Ph Na 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.76 - 1.98 (m, 4H) 2.28 -2.46 (m, 1H) 2.40 (s, 3H) 4.57 (s. 2H) 6.55 - 6.62 (m. 1H) 7.00 -7.10 (m. 2H) 7.30 - 7.40 (m. 2H) 7.52 - 7.65 (m , 3H) 8.09 (d, J=8.6 Hz, 1H) 8.26 - 8.33 (m. 1H) 10.64- 10.7 7 (br. 1H) 11.44 -11.55 (br, 1H) 524 2-F-3-CI-Ph Na 1H NMR ¢300 MHz, DMSO-D6) (5 ppm 1.71 - 1.98 (m. 4H) 2.28 -2.50 ( m. 2H) 4.56 (s. 2H) 6.57 (d. J=8.4 Hz, 1H) 7.02 - 7.24 (m. 4H) 7.38 (d, J=8.6 Hz, 2H) 7.60 (d. J=8.0 Hz. 1H 7.80 - 7.95 (m. 1H) 8.33 (d. J=2.4 Hz, 1H) 10.93 - 11.10(br, 1H) 11.32- 11.45 (br, 1H) 525 4-t~Bu~Ph Na 1H NMR (300 MHz DMSO-D6) (5 ppm 1 26 (s. 9H) V81 - 2.01 (m. 4H) 2.38 - 2.50 (m, 2H) 4.62 (s. 2H) 6.55 (d. J=8.7 Hz, 1H) 7.06 ( d, J=7.5 Hz. 2H) 7.25 (d. J=7.5 Hz. 2H) 7.34 (d, J=8.1 Hz. 2H) 7.48 - 7.60 (m, 3H) 8.33 (s, 1H) 11.17 - 11.26 (br 1H) 11.26 -11.34 (br. 1H) 526 2-Me-5-CF3-Ph Na 1H NMR ¢300 MHz. DMSO-D6) δ ppm 1.70 - 2.00 (m. 4H) 2.20 -2.45 (m. 2H) 2.42 (s. 3H) 4.57 (s, 2H) 6.63 (d. J=8.7 Hz, 1H) 7.14 (d, J=7.8 Hz, 2H) 7.23 (d. J=8.1 Hz, 1H) 7.36 (d, J =8.1 Hz, 1H) 7.41 (d, J=8.1 Hz, 2H) 7.68 (d, J=8.4 Hz, 1H) 8.21 (s, 1H) 8.33 (s, 1H) 10.47 (s, 1H) 11.30 (s, 1H) 527 3-iPr-Ph Na 1H NMR (300 MHz, DMSO-D6) δ ppm 1.20 (d, J = 5.4 Hz, 6H) 1.70 - 2. 00 (m. 4H) 2.20 - 2.50 (m, 2H) 2.81 (quint, J=6.9 Hz. 1H) 4.57 (s, 2H) 6.62 (d, J=8.7 Hz, 1H) 6.78 (d, J=7.5 Hz 1H) 7.08 -7.19 (m, 1H) 7.19 (d, J=8.1 Hz. 2H) 7.39 (d. J=9.3 Hz. 1H) 7.42 (d, J=8.4 Hz, 2H) 7.54 (s, 1H) 7.66 (d, J=8.7 Hz, 1H) 8.35 (s. 1H) 10.99 (s, 1H) 11.07 (s, 1H) 528 3-Me〇-4-C 卜 Ph Na 1H NMR ¢300 MHz, DMSO-D6 6 ppm 1.84 - 1.99 (m, 4H) 2.25 -2.58 (m. 2H) 3.82 (s, 3H) 4.64 (s, 2H) 6.54 (d. J=8.7 Hz, 1H) 7.07 (d. J=9.0 Hz) , 2H) 7.13 (d, J=8.7 Hz, 1H) 7.24 (d, J=8.4 Hz, 1H) 7.31 (d. J=8.7 Hz, 2H) 7.55 (d. J=9.0 Hz. 1H) 7.76 (s .1H) 8.35 (s, 1H) 11.37 - 1 1.53 (br, 1H) 11.64 - 11.82 (br, 1H) 529 X〇T!i Na 1H NMR (300 MHz. DMSO-D6) &lt;Sppm 1.80 - 2.05 (m, 4H) 2.35 -2.55 (m, 2H) 4.66 (s, 2H) 6.54 (d. J=8.7 Hz. 1H) 7.05 (d. J=8.1 Hz. 2H) 7,20 - 7.40 (m. 4H) 7 52 (dd, J-2.0 Hz, S.6 Hz, 1H) 7.86 (s, 1H) 8.35 (d, J=2.4 Hz. 1H) 11.58 (s, 1H) 11.95 (s , 1H) 530 3-CF3-4-Me-Ph Na 1H NMR (300 MHz. DMSO-D6) 5 ppm 1.85 - 2.02 Cm, 4H) 2.34 -2.51 (m. 5H) 4.67 (s, 2H) 6.52 (d , J=8.3 Hz, 1H) 7.04 (d, J~8.6 Hz. 2H) 7.30 (d, J=8.6 Hz. 3H). 7.52 (dd, J=2.7 Hz, 8.4 Hz. 1H) 7.71 (d, J =8.6 Hz. 1H) 8.18 (d, J=1.8 Hz, 1H) 8.35 (d, J=2.7 Hz. 1H) 11.62 - 11.68 (br, 1H) 11.95 - 12.01 (br. 1H) 531 2-Ch5-CF3 -Ph Na 1H NMR (300 MHz, DMSO-D6) (5 ppm 1.70 - 1.96 (m. 4H) 2.09 -2.44 (m, 2H) 4.53 (s, 2H) 6.63 (d, J=8.6 Hz, 1H) 7.15 (d. J=7.1 Hz. 2H) 7.30 - 7.44 (m, 3H) 7.59 - 7.73 (m. 2H) 8.30 (s, 1H) B.42 (s, 1H) 10.43 - 10.67 (br, 1H) 11.35 - 11.61 (br, 1H) -307- 200918053 [Table 1-48] 532 3-GF3-4-CN-Ph Na 1H NMR (300 MHz, DMSO-D6) ¢5 ppm 1.86 * 2.00 Cm, 4H) 2.35 -2.55 (m. 2H) 4.69 (s. 2H) 6.53 (d, J=8.7 Hz, 1H) 7.08 (d, J=8.4 Hz, 2H) 7.29 (d, J=8.1 Hz, 2H) 7.52 (d. J=8.7 Hz, 1H) 7.95 (d, J=8.7 Hz. 1H) 8.01 (d, J=8.4 Hz. 1H) 8.38 (s, 1H) 8.46 (s, 1H) 12.12 (s, 1H) 13.10 (s, 1H) 丫'ne 〇RA RB 533 2-CF3-4 - F-Ph Na 1H NMR (300 MHz, DMS 〇-D6) dppm 0.55 - 0.68 Cm, 2H) 0.88-0.96 (m. 2H) 4.54 (s, 2H) 6.80 (d, J=8.6 Hz, 1H) 7.32 (d, J=8.6 Hz. 2H) 7.47 (d, J=8.6 Hz, 2H) 7.42 - 7.63 (m, 3H) 7.78 - 7.86 (m, 1H) 8.40 (d, J=2.4 Hz, 1H) 10.10 - 10.59 (br, 1H) 11.32 - 11.84 (br, 1H) 534 2-CF3-4-C Ph Ph 1 H NMR (300 MHz, DMSO-D6) 5 ppm 0.55 - 0.70 (m. 2H) 0.85 -1.00 (m, 2H) 4.53 (s, 2H) 6.80 (d. J = 8.6 Hz, 1H) 7.34 ( d, J=8.6 Hz. 2H) 7.49 (d. J=8.6 Hz, 2H) 7.60 - 7.75 (m. 3H) 7.77 - 7.87 (m, 1H) 8.39 (s. 1H) 10.17 - 10.61 (br. 1H) 11.34 - 11.85 (br, 1H) 535 2-CI-4-CF3-Ph Na 1H NMR (300 MHz. DMSO-D6) 5 ppm 0.51 ~ 0.61 Cm, 2H) 0.88 -0.98 (m, 2H) 4.46 (s, 2H) 6.77 (d, J=8.4 Hz, 1H) 7.34 - 7.44 (m, 2H) 7.51 (d, J=7.8 Hz, 2H) 7.64 (d, J=7.5 Hz. 1H) 7.79 - 7.87 (m. 2H) 8.16 - 8.29 Cm, 1H) 8.36 (s, 1H) 536 3-CF3-4-F-Ph Na 1H NMR (300 MHz, DMSO-D6) 5 ppm 0.68 - 0.75 (m, 2H) 1.05 -1.19 (m, 2H) 4.58 (s, 2H) 6.73 (d, J = 8.4 Hz. 1H) 7.20 (dt J=8.4 Hz, 2H) 7.31 -7.41 (m. 1H) 7.38 (d, J=8.7 Hz, 2H) 7.71 (dd, J=2.7 Hz, 8.7 Hz, 1H) 7.78 - 7.85 (m. 1H) 8.24 (dd. J =2.4 Hz, 6.9 Hz. 1H) 8.42 (d, J=2.7 Hz. 1H) 11.85 - 11.92 (br. 1H) 1 1.96 - 12.05 (br. 1H) 537 2-CF3〇-Ph Na 1H NMR ¢300 MHz DMSO-D6) δ ppm 0.50 - 0.60 (m, 2H) 0.89 -0.97 (m. 2H) 4.49 (s. 2H) 6.78 (d. J=8.0 Hz. 1H) 7.08 (dd. J=7.7 Hz. 7.7 Hz. 1H) 7.20 - 7.34 (m. 2H) 7.37 (d, J=8.0 Hz, 2H) 7.52 (d, J=8.6 Hz. 2H) 7.84 (d, J=8.0 Hz, 1H) 8.00 (d, J =7.7 Hz. 1H) 8.37 Cs. 1H) 10.00 - 10.20 (.br, 1H) 10.98 - 11.18 Cbr, 1 H) 538 3-CI-4-F - Ph Na 1H NMR ¢300 MHz, DMSO-D6) &lt;5 ppm 0.67 - 0.74 (m. 2H) 1.03 - I. 10 (m, 2H) 4.57 (s. 2H) 6.72 (d, J=8.4 Hz. 1H) 7.18 (dt J=7.5 Hz. 2H) 7.25 (t, J=9.3 Hz, 1H) 7.37 (d, J=8.7 Hz. 2H) 7.50 - 7.57 (mt 1H) 7.70 (d. J=8.7 Hz. 1H) 7.88 (d, J=6.9 Hz, 1H) 8.41 (s, 1H) II. 58 - 11.65 (br, 1H) 11.86 - 11.94 (br, 1H) 539 2-CI-4-CF3〇-Ph Na 1HMMR (300 MHz.DMS〇-D6) &lt;5 ppm 0.57 - 0.65 (m, 2H &gt; 0.90 - 0.99 (m, 2H) 4.50 (s, 2H) 6.77 (d, J = 8.6 Hz. 1H) 7.33 (d, J = 8.3 Hz. 2H) 7.28 - 7.37 (m. 1H) 7.48 (d, J=8.6 Hz. 2H) 7.53 (d. J=2.4 Hz. 1H) 7.81 (dd. J=8.6 Hz. 2.4 Hz, 1H) 7.90 (d, J=8.6 Hz 1H) 8.37 (d, J=2A Hz. 1H) 10.20 - 10.30 (br, 1H) 11.30 - 11.42 (br, 1H) 540 2-Me-4-CF3〇-Ph Na 1H NMR (300 MHz, DMSO- D6) ¢5 ppm 0.60 - 0.68 (m, 2H) 0.91 -0.99 (m, 2H) 2.30 (s. 3H) 4.53 (s. 2H) 6.75 (d. J=8.4 Hz, 1H) 7.19 (d. J= 8.7 Hz, 1H) 7.13 (s, 1H) 7.22 (d. J=8.7 Hz, 2H) 7.44 (d, J=8.4 Hz. 2H) 7.61 (d, J=9.0 Hz, 1H) 7.77 (dd, J= 8,6 Hz, 2.6 Hz. 1H) 8.37 (d. J=2.7 Hz, 1H) 10.30 - 10.37 (br. 1H) 11.49 - 11.57 Cbr, 1H) 541 3-CF3〇-Ph Na 1H NMR C300 MHz, DMSO -D6) 5 ppm 0.60 - 0.69 Cm, 2H) 0.91 -1.00 (m, 2H) 4.54 (s, 2H) 6.76 (d, J=8.6 Hz. 1H) 7.04 - 7.17 (m, 3H) 7.24 (dt J= 8.6 Hz, 2H) 7.46 (d. J=8.6 Hz, 2H) 7.63 (d. J=8.3 Hz, 1H) 7.78 (d, J 8.6 Hz, 〗 H) 8.37 (d. J=2.1Hz.1H) 10.15-10.33 Cbr, 1H) 11.25- 11.61 (br, 1H) 542 cycloHexyl Na 1H NMR ¢300 MHz, DMSO-D6) 6 Ppm 0.55 - 0.64 (m, 2H) 0.90 -0.98 (m. 2H) 1.05 - 1.34 (m, 5H) 1.48 - 1.59 (m. 1H) 1.63 - 1.81 (m. 4H) 3.30 - 3.50 (m, 1H) 4.46 (s. 2H) 6.71 (d. J=8.6 Hz. 1H) 7.23 (d. J=8.6 Hz, 2H) 7.39 (d. J=8.6 Hz. 2H) 7.54 (d. J=7.7 Hz, 1H) 7.74 (dd. J=2.5 Hz, 8.5 Hz. 1H) 8.33 (d, J=2.1 Hz, 1H) 10.19 (s. 1H) -308- 200918053 [表卜49] RA RB 543 2,4-diMe-Ph Na 1H NMR (300 MHz, DMSO-D6) δ ppm 1.46 - 1.70 (m, 6H) 2.05 -2.15 (m, 2H) 2.23 (s, 3H) 2.24 (s, 3H) 4.41 (s, 2H) 6.58 (d. J=8.6 Hz, tH) 6.91 (d. J=8.0 Hz, 1H) 6.94 (s. 1H) 7.04 (d, J=8.6 Hz, 2H) 7.36 (d. J=8.6 Hz, 2H) 7.48 (d, J=7.7 Hz. 1H) 7.60 (d, J=8.3 Hz, 1H) B.29 (d. J=2.4 Hz. 1H) 10.09- 10.21 (br, 1H) 11.21 - 11.38 (br, 1H) 0v0, Ming Η M RA RB 544 2-C Bu 4-F-Ph Na 1H NMR ¢300 MHz. DMSO-D6) 5ppm 1.16 - 1.69 Cm, 8H) 1.97 -2.09 (m, 2H) 4.29 (s, 2H) 6.56 (d , J=8.5 Hz, 1H) 7.07 (d, J=8.4 Hz. 2H) 7.16 (td, J=3.0 Hz. 8.9 Hz. 1H) 7.36 (d. J=8.4 Hz, 2H) 7.39 (dd, J= 3.0 Hz, 8.7 Hz, 1H) 7.61 (dd, J= 2.4 Hz, 8.7 Hz, 1H) 7.91 (dd, J=6.0 Hz. 9.3 Hz, 1H) 8.29 (d, J=2.1 Hz, 1H) 10.50 - 10.61 (br, 1H) 11.50 - 11.63 Cbr, 1H) 丫, RS r^r0^ RA RB 545 2-C 4-F-Ph Na 1H NMR (300 MHz. DMSO-D6) 6 ppm 0.61 - 0.68 Cm, 2H) 0.92 -0.98 (m. 2H) 4.63 (s, 2H) 7.15 (td, J = 2.8 Hz. 8.6 Hz, 1H) 7.33 -7.43 (m, 3H) 7.45 (d. J=8.7 Hz, 2H) 7.59 (dd, J=5.9 Hz, 8.9 Hz. 1H) 8.82 Cs, 2H) 10.50 - 10.64 (br, 1H) 11.77 - 11.92 (br, 1H) 丫 '昍八j·^ j* I丨,厂&quot;yW F RA RB 546 2-CI - 4-F-Ph ch3 1H NMR ¢300 MHz, CDCI3) 6 ppm 1.92 - 2.21 ( m, 4H) 2.45 -2.61 (m, 2H) 3.73 (s, 3H) 4.62 (s. 2H) 6.81 (d. J=8.7 Hz. 1H) 6.94 -7.31 (m, 5H) 7.69 - 7.78 (m, 1H) 8.05 - 8.16 (m, 2H) 8.26 - 8.31 Cbr, 1H) MS(ESI): 520(M+1). 518(M-1) 548 2-CI-4-F-Ph H 1H NMR (300 MHz , DMSO-D6) (5ppm 1.83 - 2.13 (m, 4H) 2.30 -2.47 (m. 2H) 4.55 (s. 2H) 6.91 (d, J=8.7 Hz, 1H) 7.19 - 7.29 (m, 1H) 7.46 - 7.62 (m, 2H) 7.90 (d, J=8.7 Hz, 1H) 8.06 - 8.22 (m, 2H) 8.36 (s. 1H) 8.89 (s, 1H) 9.58 Cs, 1H) 12.35 - 12.44 (br, 1H) MSiESI): 506CM+1), 504(M-1) V0, , γΜ3 F RA RB 547 2-CM-F-Ph ch3 1H NMR (300 MHz, CDCI3) δ ppm 1.98 - 2.26 (m, 4 H). 2.48 -2.63 (m. 2 H), 3.74 (s. 3 H), 4.70 (s. 2 H), 6.29 - 6.36 (m. 1 H). 6.96 - 7.08 (m, 2 H)' 7.10 - 7.22 (m, 3 H), 8, 16 (dd, J = 9.2, 5.6 Hz. 1 H), 8.68 (s. 2 H) MS (ES1/APCI Dual): 521 (M+1). 519 CM-1) 549 2—CI - 4-F-Ph H 1H NMR ( 300 MHz. DMSO-D6) i5 ppm 1.83 - 2.14 (m, 4 H), 2.31 -2.47 (m. 2 H). 4.61 (s. 2 H). 7.21 (ddd. J = 9.1. 8.4, 2.9 Hz, 1 H), 7.50 (dd, J = 8.6. 3.0 Hz. 1 H). 7.61 - 7.74 (m, 2 H). 8.07 (dd, J = 9.3, 5.9 Hz, 1 H), 8.56 (s. 1 H 8.94 (s. 1 H), 9.02 (s, 2 H), 12.40 -12.52 Cbr, 1 H) MS CES1/APCI Dual): 507 (M+1), 505 (M-1) -309- 200918053 The DGAT 1 inhibitory action of the compound of the present invention was measured by the method described in the following test examples. (Test Example 1) - DGAT1 inhibition test The DGAT1 inhibition test of the test compound was carried out in accordance with the method of Sylvaine Cases et al. (PNAS. 1998 Oct; 95: 13018). Human DGAT1 was expressed in insect cells (Sf9) using Bac-to-Bac Baculovirus Expression System (Invitrogen). The cells were ultrasonically disrupted by l〇〇, 〇〇〇G (980,665 m/s2) χ1 hour telecentric The operation was obtained by the Shen Dian, and the Shen Dian was used as the human DGAT1 enzyme partition used in the analysis. A buffer containing a final concentration of 2 mM magnesium chloride, 1 mg/ml bovine serum albumin, 90 μM dimercaptoglycerol, and 100 mM ginic acid hydrochloride (ρΗ = 7.5) was prepared and added thereto in the form of dimethyl sulfoxide (DMSO). The concentration of the test compound at various concentrations was set to DMS01%, the human DGAT1 enzyme was added to make the final concentration to be lOOpg/ml, and the 14C-labeled oil 醯Coenzyme A (Muromachi drug) was added to make the final concentration 1 8 μΜ. The amount became ΙΟΟμΙ, and the solution was allowed to react at 37 ° C for 30 minutes. After the reaction is stopped by adding an equal amount of isopropanol to the reaction solution, the matrix (14C labeled oil coenzyme A) and the reaction product (i4C-labeled tridecylglycerol) contained in the reaction solution are adsorbed. The octadecyl decane resin (wakogel 50C18) was separated by dissolution with isopropanol, and the amount of the reaction product was measured by a liquid scintillation counter, and the 14C mark when the test compound was not added was added. Tri-310-200918053 The amount of mercaptoglycerol produced was determined to be 100%, and the concentration of the compound (IC5G値) in which the yield of 5〇% was inhibited in the presence of the test compound was calculated, and the hindered activity of the test compound is shown in Table 2. Further, the inhibition rate (a) when the concentration of the test compound is 10 η Μ or 1 0 0 nM by the above-described modulation method is calculated, and the inhibitory activity of the test compound is shown in Table 3-1 and Table 3 - 2. The calculation method is as follows. (1 -c -b ) X100 = ab : 14C mark when the test compound is not added, the amount of tridecylglycerol produced c: the C mark when the test compound (concentration is 1〇ηΜ or l〇〇nM) is added The results of the amount of glycerol production are shown in Table 2, Table 3-1, and Table 3-1 below. -311 - 200918053 [Table 2] Compound No. hDGATI IC50 nM Compound No. hDGATI IC50 nM Compound No. hDGATI IC50 nM Compound No. hDGATI IC50 nM 1 11 103 16 468 6.3 519 8.2 7 5.5 421 6.8 489 6.3 520 3.9 8 1.7 452 5.1 498 6.7 521 8.3 16 18 453 3.1 499 2.6 522 4.9 23 20 454 2.3 500 3.9 523 9.8 28 150 455 3.7 501 14 524 4.4 32 64 456 6.5 508 6.3 525 20 53 11 457 2.4 509 3.3 526 11 66 20 458 2.0 510 12 527 9.7 72 7.7 459 2.7 511 5.2 528 12 79 19 460 8.3 512 5.5 529 11 83 5.2 461 47 513 12 530 9.3 87 2.0 462 5.0 514 9.2 531 22 89 28 463 8.1 515 8.2 532 28 91 3.1 464 4.5 516 2.9 543 4.8 102 17 467 14 517 4.0 545 2.6 [Table 3 - 1] Compound No. 10nM hDGATI Inhibition rate (%) 100nM hDGATI Inhibition rate (%) Compound number ΙΟηΜ hDGATI Obstruction rate (%) 100nM hDGATI Obstruction rate w Compound number 10nM hDGATI Obstruction rate w 100nM hDGATI inhibition rate (%) Compound number 10nM hDGATI inhibition rate (%) 100nM hDGATI inhibition rate (%) 305 55 80 332 49 80 358 54 84 375 78 97 306 47 82 333 41 62 359 42 79 376 74 94 307 80 95 334 42 79 360 71 93 377 71 93 309 49 66 336 43 81 361 40 61 378 79 94 310 40 72 337 74 90 362 55 86 379 70 88 311 43 55 340 77 98 363 50 80 380 57 83 313 47 72 341 53 92 364 71 93 382 63 75 314 75 93 342 59 84 365 75 94 383 73 93 316 70 90 344 51 77 366 69 91 384 75 79 318 52 81 345 82 102 367 87 98 385 53 82 320 56 84 348 50 81 368 52 78 388 41 74 322 66 94 349 54 78 369 53 86 390 65 : 89 324 42 77 353 44 76 371 57 87 391 59 87 325 48 84 354 59 86 372 52 85 392 47 80 326 82 96 355 46 82 373 49 80 394 59 83 328 40 77 356 74 96 374 73 94 395 54 79 -312- 200918053 [Table 3-2] Compound No. 10nM HDGAT1 Obstruction rate (%) 100nM hDGATI Obstruction rate (%) Compound No. 10nM hDGATI Inhibition rate (%) 100nM hDGATI Inhibition rate (%) Compound number 10nM hDGATI Inhibition rate (%) 100nM hDGATI Inhibition rate (%) Compound number 10nM hDGATI Obstruction rate w 100nM hDGATI Obstruction rate (%) 396 75 86 436 76 96 469 67 100 491 68 94 397 72 92 437 59 95 470 72 96 492 64 89 398 64 89 438 56 87 471 68 95 493 71 97 399 58 87 439 69 90 472 85 99 494 65 95 400 44 75 440 66 98 473 86 99 495 72 92 401 42 77 441 73 99 474 69 94 496 66 86 403 60 86 442 65 96 475 79 97 497 80 97 404 62 88 443 60 98 476 75 92 503 72 98 405 51 80 444 45 90 477 51 85 504 60 98 406 60 91 445 52 92 478 74 95 407 72 94 446 49 90 479 63 90 408 54 89 447 71 92 480 41 76 409 56 88 448 59 94 481 66 100 41Q 49 83 450 47 84 482 52 95 411 66 88 465 78 99 483 83 102 435 82 100 466 70 95 488 63 93 (Test example 2)) - Neutral fat absorption inhibition - Neutral fat absorption inhibition of the compounds of the present invention, using SD rats (S prague - D aw 1 ey R at ) for review, male SD rats (8 weeks 齢, weight 220 -260g, Charles River, Japan) Forced oral administration (5ml/kg) of a 0.5% carboxymethylcellulose aqueous solution suspended in a compound (1mg/kg) and 20% neutral fat emulsion (IntraliP〇s 20%: Daphnia Pharmaceutical (share)), on the other hand, for the control group, forced oral administration (5ml/kg) of 0.5% carboxymethylcellulose water Liquid and 20% neutral fat latex, 1 hour after administration, the SD rats were laparotomically anesthetized by intraperitoneal administration of Pentobarbital (Nembutal: Dainippon Sumitomo Pharmaceutical Co., Ltd.), and collected through the small intestine lymphatics 20-3 0 μί of small intestinal lymph, the neutral fat concentration in the lymph was measured with a commercially available kit (triglyceride E Test Wako: Wako Pure Chemical Co., Ltd.), relative to 20% latex, 0.5% carboxyl group - 313- 200918053 Methylcellulose administration group (control group), calculated the neutral fat concentration reduction rate of the drug-administered group as a neutral fat absorption inhibitory activity, lmg/ of compound numbers 1, 7, 83, 90 The kg-administered group showed 71%, 74%, 81%, and 80% of the neutral fat absorption inhibiting activity. (Test Example 3.) - Anti-obesity effect - The anti-obesity effect of the compound of the present invention was examined using C57BL/6J mice. Male C57BL/6J mice (7 weeks sputum, body weight 20-25 g, Japan Charles river) were tested in groups of 12 horses, and each mouse was bred with free feeding and drowning during the test period, and rats of 7 weeks old were measured. The body weight is divided into 12 groups per group in such a way that the average body weight of each group is not different. After grouping, the calorie ratio of fat from the total calorie supply to each mouse is 60% of the high fat diet. The rats in the group were orally administered (5 m 1 /kg, twice a day) in a suspension of 0-5% carboxymethylcellulose aqueous solution, and the control group was orally administered (5 ml/kg, 1 day). 2 times) 0.5% aqueous solution of carboxymethylcellulose, the compound of Compound Nos. 1 and 7 was administered for 5 6 days, and the compound of Compound No. 90 was administered for 28 days, and the weight gain of each group was calculated. , the weight gain inhibition rate of the drug-administered group relative to the weight gain of the 0.5% carboxymethylcellulose administration group, and the inhibition rate of the body weight increase of the high-fat diet-loaded mice produced by the compounds of Compound Nos. 1, 7 were calculated. , 10 mg / kg of the administration system were 42.6%, 32.5%, 30 mg / kg Department of each 52.1%, 45.3%, in addition, administration Compound No. body produced high-fat food load compound 90 rats of weight gain inhibition ratio, 30mg / kg was 44.6% based administration. -314-200918053 The formulation examples of the compound of the present invention are shown below. Formulation Example 1 A granule containing the following components was produced. The compound represented by the formula (1) is 10 mg lactose 7 0 0 mg corn starch 27 4 mg HPC-I. 1 6 mp 1 0 0 0 mg The compound represented by the formula (1) and lactose are passed through a 60 mesh decoration. The corn starch is passed through a 12-inch mesh sieve, and the mixture is mixed with a V-type mixer, and a low-viscosity hydroxypropylcellulose (HPC-L) water solution is added to the mixture to form a mixture. The granulation (extrusion of the granulated pores by 〇·5 to 1 mm) was followed by drying, and the obtained dried granules were sieved with a shaker (1 2 / 60 mesh) to obtain granules. Formulation Example 2 A capsule filling powder containing the following components was produced.

Compound 1 represented by the formula (1) Or ng lactose 79η ng Corn starch 1 On ng Stearic acid bismuth 1 mi R 1OOOmg -315- 200918053 The compound represented by the formula (1) and lactose are passed through a 60 mesh sieve. , the corn house powder was passed through a 120 mesh shop', and the magnesium stearate was mixed with a ^&gt; type mixer, and 10 times of 100 mg of the powder was filled in a hard gelatin capsule No. 5. Formulation Example 3 A capsule-filling granule containing the following components was produced. Compound represented by the formula (1) 15 mg Lactose 90 mg Corn source powder 42 mg Η PC - L______3 mg 1 5 Omg The compound represented by the formula (1) and lactose are passed through a 60 mesh sieve to pass the corn starch through 1 20 mesh sieves, mixed with a V-type mixer, and added a low-viscosity hydroxypropyl cellulose (HPC-L) aqueous solution to the mixture, and the mixture is dried, granulated, and dried to obtain the obtained dry granules. The sieve was sifted through a vibrating sieve (12/60 mesh) and granulated, and 150 mg of this gel was filled in a hard gelatin capsule No. 4. Formulation Example 4 A tablet containing the following components was produced. -316- 200918053 Compound 1 represented by formula (1) 〇mg lactose 9 〇 mg microcrystalline cellulose 3 〇 mg magnesium stearate 5 mg CMC-Na 1 5 ms. 1 5 〇 mg component makes formula (1) The compound represented and lactose and microcrystalline cellulose, CMC-Na (carboxymethylcellulose sodium salt) were sieved through a 60-mesh sieve, and magnesium stearate was added to the mixture to obtain a mixture for the preparation. The mixture was directly tableted to obtain a 150 mg tablet. Formulation Example 5 An intravenous preparation was produced as follows. The compound represented by the formula (1) 100 mg of the saturated fatty acid glyceride 1000 ml The solution of the above-mentioned component is usually administered intravenously to the patient at a rate of 1 ml per minute. [Industrial Applicability] The compound of the present invention has an excellent DG AT 1 inhibitory action and can provide obesity, hyperlipidemia, hypertriglyceridemia, abnormal lipid metabolism, diabetes, arteriosclerosis, or Hyperlipidemia caused by obesity, -317- 200918053 Hypertriglyceridemia, abnormal lipid metabolism, diabetes, arteriosclerosis, or prevention and treatment of hypertension. -318-

Claims (1)

200918053 X. Patent Application ι_ A heteroarylbenzene compound represented by η, a tautomer, stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof, (In the formula (1), A represents N or CH; R1 represents a hydrogen atom, or a Cl-8 alkyl group; and R2a and R2b represent a hydrogen atom, a halogen atom, or the same or a phase selected by a group of Ci 6 alkyl groups; Q group is not phenyl (the phenyl group is unsubstituted or substituted by a Ci_8 alkyl group, a hydroxy group (_Cl_6 alkoxy group is not substituted, or &amp; one to five fluorine atoms) a group of dentate atoms, trifluoromethyl, cyano, thiol, ethoxylated, methylenedioxy (substituted with two fluorine atoms of the carbene), phenyl, C, fluorenyl The same or no base (the nodal group is unsubstituted or substituted with two fluorine atoms), naphthyl group; the oxy group is unsubstituted, or is 1 to 2 -6 alkylthio group, and Ci 6 alkylsulfonate 1 main 3 substituents), benzyl 1 to 2 C 丨 "alkyl, or, : tetrahydronaphthyl, or C3_10 cycloalkane m represents 0 or 1; -319- 200918053 n represents 〇 or 1 ; X represents not - 〇-, or -NR3- (wherein R3 represents a non-aero atom, or a Ci-8 I thiol group (the CU8 building group can be bonded to a γ carbon atom to form 5 Heterocyclic to 7 members)); Y is not C1-8 extension base (the Cl.8 The base is not substituted, or is substituted by the same or different 1 to 2 groups selected from the group consisting of a phenolic C16 alkyl group, and one of the carbon atoms of the Ci-8 stretching base may be The one of the carbon atoms of the C8 alkyl group substituted by an oxygen atom may be a member of a cyclohexane having 3 to 6 members formed by the carbon atom itself, or a heterocyclic ring of 3 to 6 members)). 2 - a heteroarylbenzene compound represented by the formula (2), a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, (Chemical Formula 2) (In the formula (2), A represents N or CH; R 1 represents a hydrogen atom, an R 2 form ΓΕΓ ΓΕΓ - atom, or a C i - 8 alkyl group; R represents a hydrogen atom, a halogen atom, or Q represents a phenyl group (this a phenyl unsubstituted alkyl group; or selected from the group consisting of &lt;^.8 alkyl, Ci-6 alkoxy (the mountain 6 alkoxy is unsubstituted, or is selected from Ci-6 alkoxy-320. 200918053 And one of the groups of the group formed by the di(C,-6 alkyl)amino group), a halogen atom, a trifluoromethyl group, a trifluoromethoxy group, a cyano group, a hydroxyl group, and a Ci·6 group. Substituted by the same or different groups of 1 to 1 of the group formed by the thiol group, benzyl (the benzyl group is unsubstituted, or substituted by 1 to 2 Cl 3 groups), or C3 -1G cycloalkyl m represents hydrazine or 1; n represents 0 or 1; X represents -0-, or -NR2- (wherein R1 represents a hydrogen atom or a Ci8 fluorenyl group (the C,-8 alkyl group can be combined with γ) a carbon atom bonded to form a 5- to 7-membered heterocyclic ring)); Y represents C, _8 alkylene (the C! -8 alkyl group is unsubstituted or is selected from the group consisting of &lt;^-6纟Substituted by the same or different 1 to 2 groups of the group formed by the hydroxy Ci6 alkyl group, the Ci 8 alkyl group One of the carbon atoms may be substituted by an oxygen atom. 'One of the carbon atoms of the Ci 8 alkyl group may be a cycloalkane containing 3 to 6 members formed by the carbon atom itself, or 3 to 6 members. a member of the heterocyclic ring)). Ο -321 - 1 · a heteroarylbenzene compound represented by the formula (3), a tautomer stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, 2 ] 200918053 (In the formula (3), A represents N or CH; R1 represents a hydrogen atom or a C8 alkyl group; R2 represents a hydrogen atom, a halogen atom, or a Ci6 alkyl group; Q represents a phenyl group (the phenyl group is not Substituted, or substituted by the same 1 to 3 groups selected from the group consisting of C!-6 alkoxy, halogen atom ' and trifluoromethyl group; γ represents 8 alkyl group (alkyl group Substituted or substituted by the same or different 1 to 2 groups selected from the group consisting of Cl_6 alkyl and hydroxy Ci 6 annoyance, one of the atoms of the Cl_s may be substituted by an oxygen atom, the C ^ _ One of the bases of the 8th courtyard can be a member of the cyclohexane containing 3 of the carbon atom itself or a heterocyclic ring of 3 to 6 members)). 4. The tautomer, stereoisomer, or pharmaceutically acceptable solvate thereof of the heteroaryl benzene compound according to the scope of the patent application, wherein the alkyl group is represented by the formula (4), an alkyl group , with or without the carbon atom of the alkyl group to 6 members, the salt or (In the formula (4), Q represents a phenyl group (the phenyl group is unsubstituted, or a Cl.8 alkyl group, a C!-6 alkoxy group, a halogen atom, a trifluoromethyl group, a triyl group, a cyano group, and a The same or different groups of the dioxy group (the methylenedioxy group is not substituted by 1 to 2 fluorine atoms) are selected from the group consisting of fluoromethoxy, or 1 to -322-200918053 3 Substituted by the base); A, Rl range defined in item 1). R2b, and Y as claimed in the patent 5. The heteroaryl benzene servant content of claim 4, the tautomer of the compound, the stereoisomer' or its medicinal herb The solvate of this class is represented by the formula (5) (In the formula (5), Q represents a phenyl group (the phenyl group is unsubstituted or is selected from a Cu alkyl group, a Ci. 6 alkoxy group, a halogen atom, a trifluoromethyl group, and a trimethoxy group). Substituted by the same or different 1 to 3 groups); R〗 represents a hydrogen atom, or a C1-3 yard; R2b represents a hydrogen atom; R2a, and A are as defined in item 4 of the scope of the patent application) . 6 A heterocyclic benzene compound according to item 5 of the patent application, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is N and R1 is hydrogen An atom, R2a is a hydrogen atom or a methyl group, and R2b is a hydrogen atom. 7. A heteroarylbenzene compound according to claim 5, a tautomer, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is CH and R1 is The hydrogen atom, R2a, and R2b are hydrogen atoms. 8. The heteroarylbenzene compound of claim 4, the tautomer, stereoisomer of the compound -323-200918053, or a pharmaceutically acceptable salt thereof or a solvate thereof, Expressed by equation (6), (In the formula (6), R1 represents a hydrogen atom or a C!-3 alkyl group; p represents an integer of 1 to 4; and A, R2a, R2b and Q are as defined in the fourth aspect of the patent application. 9. A heteroarylbenzene compound according to item 8, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is N, R1 is a hydrogen atom, R2a, and R 2b is a hydrogen atom, and Q represents a phenyl group (the phenyl group is unsubstituted or is selected from the group consisting of a C 8 alkyl group, an alkoxy group, a halogen atom, a trifluoromethyl group, and a trifluoromethoxy group). The same or different 1 to 3 substituents are substituted; p is an integer of 1 to 3. 1 〇. The heteroaryl benzene compound of claim 8 of the patent application, tautomers, stereoisomers of the compound Or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein A is CH, R1 is a hydrogen atom, R2a and R2b are a hydrogen atom, and P is an integer. 11. Miscellaneous as in claim 8 An arylbenzene compound, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is N, R1 Is a hydrogen atom, R 2a is methyl-324-200918053, a chlorine atom, or a fluorine atom, R 2b is a hydrogen atom, a chlorine atom, or a fluorine atom, and Q represents a phenyl group (the phenyl group is unsubstituted or selected from Ci8 alkane) Substituted by the same or different i to 3 groups of the group of C!-6 alkoxy, halogen atom, difluoromethyl, and trifluoromethoxy; p is an integer of 3 . 12. The heteroarylbenzene compound according to item 8 of the patent application, the tautomer 'stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is CH, R1 is a hydrogen atom, R2a is a methyl group, a chlorine atom, or a fluorine atom, R2b is a hydrogen atom, a chlorine atom, or a gas atom 'Q represents a phenyl group (the phenyl group is unsubstituted, or is selected from a ci-8 base, C&quot; The group consisting of an oxy group, a self-priming atom, a trifluoromethyl group, and a trifluoromethoxy group is the same or not substituted with three groups; an integer of p贞W. a benzene compound, such as a tautomer, a stereoisomer, or a pharmaceutically acceptable salt thereof, or a solvent thereof a compound represented by the formula (7), [Chem. 7] (In the formula (7), 'Q represents a phenyl group (the benzene is substituted with an aryl group, or is selected from a Cy alkyl group, a C, -6 alkoxy group, a hydroxy element, a monomethyl group, and a trifluoromethoxy group). The same or different groups of groups formed by the base are replaced by J &lt;bases; A-325-200918053, R1, R2a, R2b, and Y are as defined in the first item of the patent application scope). 14. A heteroarylbenzene compound according to claim 13 of the patent application, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein (8) Said, (In the formula (8), R1 represents a hydrogen atom or a Ci-3 alkyl group; R2a represents a hydrogen atom; and R2b, A and Q are as defined in the first aspect of the patent application scope). A heteroarylbenzene compound according to claim 14 of the patent application, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is N, R1 is a hydrogen atom, and R2a and R2b are a hydrogen atom. 16. The heteroarylbenzene compound of claim 14, the tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, or a solvate thereof, wherein A is CH and R1 is The hydrogen atom, R2a, and R2b are hydrogen atoms. 17. A heteroarylbenzene compound according to claim 13 of the patent application, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein (9) Said, -326- 200918053 (In the formula (9), R1 represents a hydrogen atom or a Ci-3 yard; P represents an integer of from 1 to 4; and R2a represents a hydrogen atom: R2b, A and Q are as defined in claim 13 of the patent application) . 18. The heteroarylbenzene compound of claim 17, wherein the tautomer, stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is N, R1 is a hydrogen atom, R2a and R2b are a hydrogen atom, and P is an integer of 1 to 3. 19. The heteroarylbenzene compound of claim 17, wherein the tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, or a solvate thereof, wherein A is CH, R1 is a hydrogen atom, R2a and R2b are a hydrogen atom, and P is an integer of 1 to 3. 20. The heteroarylbenzene compound according to claim 1, wherein the tautomer, the stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, is a formula (1) Said, -327- 200918053 [化1 〇] (10) (In the formula (10), Q, A, R1, R2a, R2b, and/or as defined in the first paragraph of the patent application). 2 1. A heteroarylbenzene compound according to claim 20, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Said, [Chemical 1 1] (11) (In the formula (11), R1 represents a hydrogen atom or a C!-3 alkyl group; Q represents a phenyl group (the phenyl group is unsubstituted or is selected from a 6.8 alkyl group, a ^6 alkoxy group, a halogen) Substituted by the same or different 1 to 3 groups of atoms, trifluoromethyl groups, and trifluoromethoxy groups; R2a, and R2b represent a hydrogen atom; as in the scope of claim 20 definition). 22. A heteroarylbenzene compound according to claim 21, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein A is N, R1 It is a hydrogen atom. -328- 200918053 2 3. The tautomer, stereoisomer, or its medicinal or solvate of the heteroaryl 3 compound as claimed in claim 21 wherein A is CH' R1 is hydrogen 2. The tautomer, stereoisomer, or a genus thereof or a solvate thereof of the heteroaryl 3 compound of claim 20, which is represented by the formula (1 2 ), The above allowed salt B. Compound, salt permissible (In the formula (12), R1 represents a hydrogen atom or an integer of Cm alkyl group, and Q'A, R2a, and R2b are as defined in the patent application). 2 5 . The tautomer, stereoisomer, or pharmaceutically acceptable or solvate thereof of the heteroaryl benzene compound of claim 24, wherein A is N, and R 1 is a hydrogen atom R 2b is a hydrogen atom 'Q' represents a phenyl group (the phenyl group is unsubstituted with a Ci-8, a Cl-6, a halogen atom, a dihalomethyloxy group, or the same or different 1 to 3 bases) a tetrahydronaphthyl group; P is an integer of 1 to 3. 26. A tautomer, a stereoisomer, or a pharmacate thereof or a solvate thereof, as described in claim 24 of the heteroarylbenzene compound. 'where A is CH ' R1 is hydrogenogen -329-; P represents the compound of 1-4, the above-mentioned salt, R2a, and or selected from; and trifluoromethyl hydrazine And the i compound, the above-mentioned salt, R2a, and 200918053 R2b are hydrogen atoms, and p is an integer of 1 to 3. 27_ If the patent application amount is 24 1 杂 of the heteroarylbenzene compound, the tautomer of the compound, the stereoisomer, (4) the pharmaceutically acceptable salt or the solvate thereof, the towel A is N, and R1 is chlorine. Atom, R 2a is a methyl group, a chlorine atom, or a fluorine atom, and is a _ sub, a chlorine atom, or a fluorine atom, and Q represents a phenyl group (the phenyl group is unsubstituted or selected from the group consisting of "completely, complete"; P is the number of substitutions of 1 or 3 groups of the same or different groups of 1 C&quot;homoyl-halogen atom, trifluoromethyl-, and trifluoromethoxy. 28. Patent Application No. 24 A heteroarylbenzene compound, a tautomer, an isomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein A is CH, Ri stomach is methyl, chlorine atom, or a fluorine atom, R is a hydrogen atom, a chlorine atom, or a fluorine atom, and Q represents a phenyl group (the phenyl group is unsubstituted or is selected from a Ci 8 alkyl group, a Cl-6 alkoxy group, a halogen atom, a difluoromethyl group). And the same or different 1 to 3 groups of the group formed by the trifluoromethoxy group are substituted); 1) is an integer. 2 9 _ - a heteroarylbenzene compound, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, 2-({5-[4-( { 〔2_methoxy) 5- 5-(trifluoromethyl)phenyl]amine]methylamino}amino)phenyl]pyridin-2-yl}oxy)-2-methylpropionic acid 3- { 〔5-(4-{ 〔 (2,3 -methoxyphenyl)aminomethylindenyl]amino}phenyl) succinyl D-l-yl]S-female 丨-2,2-dimethylpropionic acid-330- 200918053 3-{[5-(4-{[(2,4-dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]amino} -2,2-dimethyl 3-{[5-(4-{[(2-Chlorophenyl)aminomethylindolyl)aminophenyl)pyridin-2-yl]amino}-2,2-dimethyl Propionate 3-{[5-(4-{[(2,3-dimethoxyphenyl)aminocarbamoyl]amino}phenyl)pyrene is more than D-but-2-yloxy] -2 , 2 - 3-methylpropionic acid 3-indole [5-(4-{ 〔(2-chlorophenyl)aminocarbamoyl]amino}phenyl)D than H疋-2-yl]oxy} 2,2-I-methylpropionic acid 3-{[5-(4-{ 〔(3-ethylphenyl)aminomethylindenyl)amino}phenyl)pyrene-throm-2-yloxy } -2 ,2-Methylpropionic acid 3-{ [ 5-(4-{ 〔(3,5-dimethylphenyl)aminomethylmethyl)amino}phenyl)pyridin-2-yl]oxy} -2,2-dimethylpropionic acid 3-{[5-(4-{[(2,4-methylamino)amino)carboxylic acid]amino}phenyl)indole ratio D-but-2-yl Oxy}}2,2-methylpropionic acid 3-{[5-(4-{[(2-ethylphenyl)aminomethylindolyl]amino}phenyl)pyridin-2-yl] Oxygen} -2,2-dimethylpropionic acid. 30. A heteroarylbenzene compound, a tautomer, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof or a solvate thereof, 1- ( { [ 5- ( 4- { 〔(2,4-Dimethylphenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]amino}methyl)cyclopropanecarboxylic acid 1- ( { ( 5- ( 4 - { 〔(2-Chlorophenyl)aminomethylindolyl}amino}phenyl)pyridin-2-yl]amino}methyl)cyclopropanecarboxylic acid 1- ( { [ 5- ( 4- { 〔 (2,4-dimethylphenyl)aminocarbamimidylamine-331 - 200918053 phenyl}pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1- ( { 〔5-( 4-{[(2,4-dimethylphenyl)aminomethane]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5- (4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-({[5- (4-{[(3,5-Dimethylphenyl)aminocarbamoyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1- [ ( {5- (4-( { methoxy- 5-(trifluoromethyl)phenyl)amine 1,2-[ { 5-(4-{ 〔(2,3-dimethoxyphenyl)) Aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { [ 5- ( 4- { 〔(2-chlorophenyl)aminocarbamidine) 1-( { 〔5-(4-{ 〔(2-ethylphenyl)aminocarbamimidyl)amine 1-( { 〔5-(4-{ 〔(2-methoxy-5-methylphenyl)aminocarbamidine) phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid Alkylamino}phenyl)pyrimidin-2-yloxymethyl}cyclopropanecarboxylic acid. '3 1 . - a heteroarylbenzene compound as described below, a tautomer of the compound, a stereoisomeric a construct, or a pharmaceutically acceptable salt thereof, or a solvate thereof, 1-( { 〔5-(4-{ 〔(2-chloro-4-fluoro-5-methylphenyl)aminocarbinyl) Amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid ({[5-(4-{[(2-chloro-4-fluorophenyl))aminocarbazinyl) Amino-332- 200918053 }phenyl)pyrimidin-2-yl]oxy }methyl) 1-( { 〔5-(4-{ 〔(3 - chloro-4- yl)phenyl)pyrimidin-2-yl)oxy}methyl) 1- ( { 〔 5- ( 4- { [(3-Chlorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutan-1-( { 〔 5-(4-{ 〔(2-fluoro-5-methyl}phenyl)pyrimidine-2 -yloxy}methyl 1 ( { 〔5-(4-{ 〔(3 - chloro-2- phenyl)phenyl)pyrimidin-2-yl)oxy}methyl) 1-[ ( { 5-[ 4 -( { [4-Methyl-3-methylindenyl}amino)phenyl]pyrimidin-2-yl 1-[( { 5- [ 4- ( { 〔 4-fluoro-3-(indenyl)amine Phenylpyrimidin-2-yl} 1-( { 〔 5-( 4- { 〔(4-chloro-3-methylamino}phenyl)pyrimidin-2-yl)oxy}methyl 1-( { [ 5- ( 4- { 〔(3-chloro-4-methylamino}phenyl)pyrimidin-2-yl]oxy}methyl 1-[( { 5 -[ 4 - ( { 〔 3 -(propane- } Amino)phenyl]pyrimidin-2-yl}oxy) 1-[({ 5-[4-({[4-fluoro-2-(indolyl)amino)phenyl]pyrimidin-2-yl} 1 - 〔( { 5- 〔 4-( { 〔2-Fluoro-5-(indenyl)amino)phenyl]pyrimidin-2-yl} 卜 [({ 5- 〔 4- ( { 〔 2-methyl -5- Cyclobutanecarboxylic acid phenyl)aminomethylmercapto]aminocyclobutane Carboxylic acid)aminomethylmercapto]amino}phenyl carboxylic acid phenyl)aminomethyl hydrazino] amide) cyclobutane carboxylic acid phenyl) aminomethyl hydrazino] aminocyclobutane carboxylic acid ( Trifluoromethyl)phenyl]amino}oxy}methyl]cyclobutanecarboxylic acid trifluoromethyl)phenyl]aminomethoxy)methyl]cyclobutanecarboxylic acid oxyphenyl)amino Indenyl)cyclobutanecarboxylic acid oxyphenyl)aminocarbinyl]yl)cyclobutanecarboxylic acid 2-yl)phenyl]aminocarboxamylmethyl]cyclobutanecarboxylic acid trifluoro Methyl)phenyl]amino]methoxy)methyl]cyclobutanecarboxylic acid trifluoromethyl)phenyl]aminomethoxy)methyl]cyclobutanecarboxylic acid (trifluoromethyl)phenyl]amine Base-333- 200918053 formazanylamino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2 - gas-5-) Each base) aminomethyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-( { [3-(trifluoro]) Methoxy)phenyl]aminomethylindenyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[ ( {5-[4-( { 〔4- Trifluoro Phenyl]amino]aminomethylindenyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3-chlorophenyl) Aminomethylamino]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-methoxy) Phenyl)aminomethylmercapto]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1 ( { 〔5-(4-{ 〔 (3 - chloro-4-fluoro) Phenyl)aminoglycolyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1·( { [5-(4-( 〔 2- per-5-A) Alkyl)aminomethyl}amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-[({5-[4-( { [4-fluoro-3-() Trifluoromethyl)phenyl]aminocarbamimidylamino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[ ( {5-[4-( { 〔4- Fluoro-2-(trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[ ( {5-[4- ( { [2-fluoro-5-(trifluoromethyl)phenyl]aminomethylindenyl}amino)phenyl]pyrimidin-2-yl}oxy)A 】 cyclopropanecarboxylic acid 1-[({5-[4-({[3-(trifluoromethoxy)phenyl]aminomethyl)}amino)phenyl]pyrimidin-2-yl}oxy) Methyl]cyclopropanecarboxylic acid 1-[({5-[4-({[2-methyl-4-(trifluoromethoxy)phenyl)amine-334- 200918053)) Phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1_[({5-[4-({[[2-chloro-4-(2-dimethyloxy)phenyl]aminocarboxamidine) 1-[(5-[4-({[2-(trifluoromethoxy)phenyl])amino]amino]phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid Mercapto}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)amino Methylamino]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-fluoro-5-methylphenyl)) Aminomethylamino]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1_( { 〔5-(4-{ 〔 (2 - chloro-4- per benzyl) Aminomethyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylate sodium ([5-[4- ({[2-fluoro-5-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { [5-(4-{ 〔(2- gas-4-carbyl)aminoalkyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1_( { [5-(4-{ 〔(5-Gas-2-Gasyl)aminocarboxylic acid]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { [5-(4-{ 〔(2-Chloro-5-fluorophenyl)aminomethane]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid {5-[4-( { 〔3-(Trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1 -[({5-[4-( { [4-fluoro-2-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl] Cyclopropanecarboxylic acid-335- 200918053 l-[({5-[4-({[4-Chloro-2-(trifluoromethyl)phenyl]aminocarbamoyl)amino)phenyl]pyridine- 2-[}}oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-({[2-chloro-4-(trifluoromethyl)phenyl])amino) 1-[(5-[4-({[4-(3-(trifluoromethyl))phenyl)]phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid Aminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-({[2-(trifluoromethoxy))) Phenyl]aminomethylmercapto}amino)phenyl]pyran-2-yl}oxy)methyl]cyclopropane decanoic acid 1 · ( { [ 5 - ( 4 - { 〔 (3 - gas-4) - gas-based) aminomethyl aryl] amine} phenyl) pyridine-2 _ yl] oxy} methyl) cyclopropanecarboxylic acid 1-[(丨5-[4-( { 〔2-chloro-4 -(Trifluoromethoxy)phenyl]aminomethylindenyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-(丨) [2-methyl-4-(trifluoromethoxy)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[ ( { 5-[4-( { 〔3-(Trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1- { [(5-{4-[(Cyclohexylaminomethylmethyl)amino]phenyl}pyridin-2-yl)oxy]methyl} ring Alkylcarboxylic acid 1- C ( { 5- [ 4-( { 〔2-fluoro-5-(trifluoromethyl)phenyl]aminomethylmethyl}amino)phenyl]pyridin-2-yl}oxy )methyl]cyclopropanecarboxylic acid 1-[( { 5- [ 4-( { 〔4-(trifluoromethoxy)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl Oxygen)methyl]cyclopropanecarboxylic acid 1-( { ( 5-(4-{ 〔(2,4-dimethylphenyl)aminomethylindenyl)amine-336- 200918053 phenyl}pyridine 2-(yl)oxy}methyl)cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethylindenyl)amino}phenyl) Pyridin-2-yl]oxy}methyl)cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-fluoro-5-methylphenyl)aminomethylindenyl)amino}benzene 1-({-(4-{[(2,4-dimethylphenyl)aminomethylindenyl]amino)}pyridin-2-yloxy]methyl)cyclopentanecarboxylic acid} Phenyl)pyridin-2-yl]oxy}methyl)cyclohexanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethylindenyl)amine Phenyl)pyridin-2-yl]oxy}methyl)cyclohexanecarboxylic acid 1-[({5-[4-( { [4-chloro-2-(trifluoromethyl)phenyl])amine Sodium mercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(4-fluoro-3-methylphenyl) Aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium 1-( { 〔5-(4-{ 〔 (2-bromo-5-) Sodium phenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔 (2 - gas - 4-[5-methyl-5-methylphenyl)aminomethyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-[({5-[4-( {[3-(Trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid sodium 1-( ({5-( 4-( { 〔4-chloro-3-(trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate 1 -( { 〔5-(4-{ 〔(2-Fluoro-5-methylphenyl)aminocarbamoyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate Sodium 1-( { [ 5-(4-{ 〔(3-methylphenyl)aminomethylmethyl)amino} -337- 200918053 Phenyl)pyridin-2-yl]oxanium Sodium Cyclobutanecarboxylate 1-[({5-[4-( { 〔2-chloro-4-(di-methoxy)))]aminomethyl]amino)phenyl]pyridine Sodium 2-yl}oxy)methyl]cyclobutanecarboxylate 1-[({5-[4-({[[2-methyl-4-(trifluoromethoxy)phenyl]]amino) Sodium (amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate 1 - ( { [ 5 - ( 4 - { 〔 ( 2,5- _ chlorophenyl)) Sodium]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(3 - chlorophenyl)aminocarboxyl) Sodium]amino(phenyl)pyridin-2-yloxy]methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔( 3,5- —•)) Sodium]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔(3-chloro-4-methoxyphenyl) Aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium 1-( { 〔5-(4-{ 〔(4-cyano-2-) Sodium phenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-( { 〔5-(4-{ 〔 (3-chloro Sodium 2-fluorophenyl)aminomercapto]amino}phenyl)pyridin-2-yl]oxaniummethyl)cyclobutanecarboxylate 1- ( { 〔 5- ( 4- { 〔 4 -tert-butylphenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid sodium 1-[ ( {5-[4-( { 〔 2-Methyl-5-(dioxamethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid sodium-338- 200918053 l -[({5-[ 4-(丨[3-(Proton-2-yl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutane Sodium carboxylate 1-( { 〔5-(4-{ 〔(4-chloro-3-methoxyphenyl)aminomethylindenyl)amino}phenyl)pyridin-2-yl]oxy}methyl Sodium cyclobutanecarboxylate 1-({[5-(4-{[(2,2-difluoro-1,3-benzodioxa-5-yl))aminomethylindenyl]amino} Sodium phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate 1-[({5-[4-( { 〔4-methyl-3-(trifluoromethyl)phenyl)amine) Sodium methylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid sodium 1-[({5-[4-( { [2-chloro- 5-(trifluoro]) Sodium methyl)phenyl]aminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate 1-[({5-[4-( { 〔4- Cyano 3-(trifluoromethyl)phenyl]aminocarbamimidyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid sodium 1-( { [5- (4-{(2,4-Dimethylphenyl)aminomethane)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopentanecarboxylate. 32. A heteroarylbenzene compound, a tautomer, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof or a solvate thereof, 1-( { 〔5-(4- { 〔(2-Chloro-4-fluorophenyl)aminomethylindenyl]amino}-3-fluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔 5-(4-{ 〔(2-chloro-5-fluorophenyl)aminomethylindolyl]amino}-3-fluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid -339- 200918053 卜[({5-[3-Fluoro-4-({[2-fluoro-5-(trifluoromethyl)phenyl]aminocarbamoyl)amino)phenyl]pyrimidine-2 -yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(3-fluoro-4-{ 〔(2-fluoro-5-methylphenyl)aminomethylindenyl)amine} Phenyl)pyrimidin-2-yl]oxo}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluoro(yl)aminomethyl) -3,5-difluorophenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl) Aminomethylamino]amino}-3-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5- (4-{ 〔(2-Chloro-4-fluorophenyl)aminomethylindolyl)-amino-2 -oxyphenyl)-indolyl-2-yloxy}methyl) Acid 1-( { 〔5-(2 -chloro-4-{ 〔(2- gas-4 - per-benzyl)-aminomethyl)amino}phenyl)pyridin-2-yl]oxy}methyl Cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethylindolyl)amino} -2-methylphenyl)pyridine-2- 1-( { 〔5-(4-{ 〔(2-chloro-5-fluorophenyl)aminomethylindenyl)amino} _3_fluorophenyl) Pyridine-2-yloxy}methyl)cyclobutanecarboxylic acid 1-[({5-[3-fluoro-4-({[2-fluoro-5-(trifluoromethyl)phenyl])) Mercaptoamino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid ({[-(3-fluoro-4-{[(2-fluoro-5-methyl) Phenyl)aminomethylmercapto]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (2-chloro-5-) Parental) Aminocarboxylic acid]amino} -2-fluorophenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid-340- 200918053 l-[ ( {5-[2- Fluorine- 4-( { 〔2-fluoro- 5-( Trifluoromethyl)phenyl]aminomethylamino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(2-chloro-4-)丨[(2- gas-5-ocylphenyl)aminoglycan]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[ ( {5-[2 -Chloro-4-( { [fluoro] 5-(trifluoromethyl)phenyl]aminocarbamoyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylate Acid 1-( { 〔5-(4-{ 〔(2-chloro-4-fluorophenyl)aminomethylindolyl)amino} -2,5-difluorophenyl)pyridin-2-yl]oxy }Methyl)cyclobutanecarboxylic acid. 3. A heteroarylbenzene compound, a tautomer, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof or a solvate thereof, 3- ( { 5- [ 4 - ( { 〔4-chloro-3-(trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)-2,2-dimethylpropionic acid 3-{ [5 -(4-{ 〔(3,4-dichlorophenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}-2,2-dimethylpropanoic acid 2.2- _methyl- 3- ({5-[4-( { 〔3-(Dimethyl)phenyl)indolyl)amino)phenyl]pyrimidin-2-yl}oxy)propionic acid 2.2-dimethyl-3-({ 5-[4-({[3-(Trifluoromethoxy)phenyl]carbonyl]amino)phenyl]pyrimidin-2-yl}oxy)propionic acid 3 - { 〔5-(4-{ 〔 3-chloro-4-methyl-based) ylamino}phenyl)pyrimidin-2-yl]oxy} -2,2-dimethylpropionic acid 3- ( { 5- [ 4- ( { [4 -Chloro-3-(trifluoromethyl)phenyl]carbonyl}amine-341 - 200918053 phenyl)pyridin-2-yl}oxy)-2,2-dimethylpropionic acid 3-{ [5 -(4-{ 〔(3- gas-4-methylphenyl)ornyl]amino}phenyl)pyridin-2-yl]oxy}-2,2-dimethylpropionic acid 3-{ (5 - (4-{ 〔( 3,4- _Chloryl) yl)amino}yl) pyridin-2-yl]oxy}-2,2-dimethylpropanoic acid 2.2-dimethyl-3-( {5-[4-({[3-(Trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyridin-2-yl}oxy)propanoic acid 2.2-dimethyl-3-({5- [4-({[3-(Trifluoromethoxy)phenyl]carbonyl]amino)phenyl]pyridin-2-yl}oxy)propanoic acid. 34. A heteroarylbenzene compound as described below, a tautomer, a stereoisomer, or a pharmaceutically acceptable salt thereof or a solvate thereof, of the compound [(5-[4-({[3-(trifluoromethoxy)phenyl))) 】carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-chloro-4-methylphenyl)carbonyl) Amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-({[[4-(3-(2-()))) Oral base}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[({5-[4-({[3-(trifluoromethyl)phenyl)]] Carbonyl}amino)phenyl]pyrimidin-2-ylindoleoxy)methyl]cyclobutanecarboxylic acid 1- ( { 〔5-(4 -{[(3,4-dichlorophenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-{ 〔 (5-{4-[ (5 ,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyrimidin-2-yl)oxy]methyl}cyclobutanecarboxylic acid-342 - 200918053 l-[ ( {5-[ 4-( { 〔3-(propyl-2-yl)phenyl)phenyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5- (4-{ 〔(3-Chloro-4-methoxyphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[ ( {5-[ 4-( { 〔3-(Trifluoromethoxy)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4- { 〔(4-Fluoro-3-methylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 ( 3-chloro-4-methylphenyl)carbonyl]amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-[( {5-[4-( { [4-chloro -3-(Trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1- ( ( { 5- [ 4- ( { [3- ( Fluoromethyl)phenyl]carbonyl}amino)phenyl]pyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3,4-dichlorobenzene) Carbonyl]amino]phenyl}pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-丨[(3-chloro-4-fluorophenyl)carbonyl) Amino}phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3,4-dimethylphenyl)carbonyl)amino}benzene Substrate)-2-denyl-2-oxo-oxymethyl) Phenyl}pyrimidin-2-yl)oxy]methyl}cyclopropanecarboxylic acid 1-[({5-[4-({[[3-(propan-2-yl)phenyl)carbonyl]amino)benzene) Aminopyrimidin-2-yl}oxy)methyl]cyclopropanecarboxylic acid-343- 200918053 1_( { 〔5-(4-{ 〔(3 - gas-4-methoxyphenyl) yl) Phenyl)pyrimidin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-[({5-[4-({[3-(trifluoromethyl)phenyl)carbonyl)amino)phenyl) Pyrimidine-2-yl}oxy)methyl]cyclopentanecarboxylic acid 1-( { 〔5-(4-{ 〔(4-t-3-methylphenyl)indolyl)amino} 1-({-(4-{[(3-fluoro-4-methylphenyl)carbonyl)amino}phenyl))))pyridin-2-yloxy]methyl)cyclobutanecarboxylic acid Pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-({[[4-fluoro-3-(trifluoromethyl)phenyl)carbonyl)]amino)benzene 1-( { 〔5-(4-{ 〔(3,5-difluorophenyl)carbonyl)amino}phenyl)pyridine-(pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid- 2-(yl)oxy}methyl)cyclobutanecarboxylic acid 1-( {[ 5-(4- { 〔(2,2-difluoro-1,3-benzodioxan-5-yl)carbonyl) Amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1_[({5-[4-({[2-methoxy-3-(dimethyl))phenyl) a few amino}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid [(5-[4-( { [2-methoxy-5-trifluoromethyl]) Phenyl]carbonyl]amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[({5-[4-( { [3-(trifluoromethoxy) Phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1_( { 〔5-(4-{ 〔(3- gas-4-methylphenyl) Mine base Amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid [(5-[4-( {[ 3-(1,1,2,2-tetrafluoroethoxy) Phenyl]carbonyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid-344- 200918053 1-( { 〔5-(4-{ 〔 (4-methoxy 3-methylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3,4- Diethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-( { 〔 fluoro-4-) (trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1- ( { 〔 5- ( 4- { 〔 ( 3-chlorobenzene) Carbonyl]amino]phenyl}pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[({5-[4-( { 〔3-(dimethyl)phenyl)] Mercapto}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3,5-dichlorophenyl)carbonyl)amine 1-[(5-[4-({[4-(trifluoromethoxy)phenyl)carbonyl)amine)]-phenyl]pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid Phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔(3-methoxyphenyl)carbonyl)amino}phenyl) Pyridin-2-yloxy}methyl)cyclobutanecarboxylic acid 1 · ( { 〔5-(4-{ 〔(3-methylphenyl))amino}}}}pyridin-2-yl] Oximemethyl)cyclobutanecarboxylic acid. 1-( { 〔5-(4-{ 〔(3,4-Dichlorophenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}A 1-{[(5-{4-[(n-2-yl)yl)amino]yl}}pyridin-2-yl)oxy]methyl}cyclobutane Carboxylic acid 1-( { 〔5-(4-{ 〔(3 -chloro-4-syryptyl)-yl)amino}yl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylate Acid-345- 200918053 1-( { 〔5-(4-{ 〔(3,4-Dimethylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutane Carboxylic acid 1-( { 〔5-(4-{ 〔(4-ethylphenyl)carbonyl)amino}phenyl)pyridin-2-yl]oxanylmethyl)cyclobutanecarboxylic acid 1-[ ( {5-[4-( { 〔4-methyl-3-(trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutane Acid 1- { 〔( 5- { 4-[(biphenyl-3-ylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid 1-( { 〔5- (4-{ 〔(3,5-Dimethylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4- {[(3-Methoxy-4-methylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid b ({[5-(4-{ [(3-Chloro-4-methoxyphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-( { 〔5-(4-{ 〔 (4- gas-3-methylphenyl)hydrazino]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-{ 〔 (5-{4-[ (5 ,6,7,8-tetrahydronaphthalen-2-ylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclobutanecarboxylic acid 1-[ ( {5-[4-( { [3-(Propan-2-yl)phenyl]oleyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1 - L ( { 5 -[ 4 -( [[3-(methylsulfanyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[({5-[4·( { [4-chloro 3-(trifluoromethyl)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclobutanecarboxylic acid-346- 200918053 1-( { 〔5-(4- {[(3-Aminophenyl)indolyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclobutanecarboxylic acid 1-[ ( {5-[4-( { [3- Trifluoromethoxy)phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (4-fluoro-3) -Methylphenyl)carbonyl]amino}phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3 - gas-4-methyl) Each group]amino]phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1- [ ( { 5- [ 4- ( { [4-chloro-3-(trifluoromethyl) Phenyl]carbonyl}amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-[({5-[4-( { 〔3-(trifluoromethyl)phenyl) 】carbonyl]amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3,4-dichlorophenyl)carbonyl)amino }phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔 (3,4-dimethylbenzene) Carbonyl]amino]phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3 - chloro-4-3⁄4 yl) fluorenyl) Amino}benzamine]卩 Π -2 -2 - - -2 -2 -2 -2 -2 -2 -2 1- 1- 1- 1- 1- 1- 1- 1- 1-{ 〔 -ylcarbonyl)amino]phenyl}pyridin-2-yl)oxy]methyl}cyclopropanecarboxylic acid [(5-[4-({[3-(propyl)-2-yl))] Phenyl]-amino)phenyl]pyridin-2-yl}oxy)methyl]cyclopropanecarboxylic acid 1-( { 〔5-(4-{ 〔(3 -chloro-4-methoxyphenyl)) Amino] phenyl)pyridin-2-yl]oxy}methyl)cyclopropanecarboxylic acid-347- 200918053 l-[({5-[4-( { 〔3-(trifluoromethyl)benzene) Alkyl)phenyl]pyridin-2-ylindoleoxy)methyl]cyclopentanecarboxylic acid. 3 5. The heteroarylbenzene compound described below, a tautomer, a stereoisomer of the compound, or a pharmaceutically acceptable salt thereof or a solvate thereof, 1-[({5-[ 3-fluoro-4-( { 〔3 ·(trifluoromethyl)phenyl)carbonyl}amino)phenyl]pyrimidine-2-yl}oxy)methyl]cyclobutanecarboxylic acid 1-[({5 -[3-Ga-4-({[3-(dioxamethyl)benzyl]yl}amino)phenyl]pyridine-2-yl}oxy)methyl]cyclobutanecarboxylic acid. 3 6 - a medicine which is characterized by a heteroarylbenzene compound according to any one of claims 1 to 35, a tautomer of the compound, a stereoisomer, or a pharmaceutically acceptable substance thereof A salt or such a solvate is used as an active ingredient. 3 7 · A pharmaceutical product of claim 36, which is used for the prevention or treatment of a disease or condition which can be ameliorated by the inhibition of D G A T 1 . 38. The medicine of claim 37, which is obesity, hyperlipidemia, hypertriglyceridemia, abnormal lipid metabolism, diabetes, arteriosclerosis, or obesity caused by hyperlipemia Disease, hypertriglyceridemia, abnormal lipid metabolism, diabetes, arteriosclerosis, or prevention and treatment of hypertension. -348- 200918053 VII. Designation of representative drawings: (1) The representative representative of the case is: No (2), the symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best indication of the characteristics of the invention. Chemical formula: -5-