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WO2010064300A1 - Composition for treatment of esophageal cancer - Google Patents

Composition for treatment of esophageal cancer Download PDF

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Publication number
WO2010064300A1
WO2010064300A1 PCT/JP2008/071881 JP2008071881W WO2010064300A1 WO 2010064300 A1 WO2010064300 A1 WO 2010064300A1 JP 2008071881 W JP2008071881 W JP 2008071881W WO 2010064300 A1 WO2010064300 A1 WO 2010064300A1
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WO
WIPO (PCT)
Prior art keywords
group
amino
fluorophenyl
substituent
oxy
Prior art date
Application number
PCT/JP2008/071881
Other languages
French (fr)
Japanese (ja)
Inventor
浩 尾葉石
学之 中川
Original Assignee
エーザイ・アール・アンド・ディー・マネジメント株式会社
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Application filed by エーザイ・アール・アンド・ディー・マネジメント株式会社 filed Critical エーザイ・アール・アンド・ディー・マネジメント株式会社
Priority to PCT/JP2008/071881 priority Critical patent/WO2010064300A1/en
Publication of WO2010064300A1 publication Critical patent/WO2010064300A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • the present invention relates to esophageal cancer containing novel pyridine derivatives and pyrimidine derivatives or salts thereof or hydrates thereof having hepatocyte growth factor receptor inhibitory action, antitumor action, angiogenesis inhibitory action, cancer metastasis inhibitory action, etc. It relates to a therapeutic composition.
  • HGFR Hepatocyte growth factor receptor
  • pancreatic cancer stomach cancer, colon cancer, breast cancer, prostate cancer, lung cancer, kidney cancer, brain tumor, ovarian cancer, and esophageal cancer.
  • HGF hepatocyte growth factor
  • HGFR is also expressed in vascular endothelial cells, and HGF stimulates HGFR and promotes proliferation and migration of vascular endothelial cells, and thus has been reported to be involved in tumor angiogenesis (Non-Patent Document). 2). Furthermore, it has been reported that NK4, which is an HGF antagonist peptide, inhibits cancer cell invasion and inhibits tumor angiogenesis by blocking the HGF-HGFR signal (Non-Patent Documents 3 and 4). Therefore, a compound having an HGFR inhibitory action is expected to be useful as an antitumor agent, an angiogenesis inhibitor or a cancer metastasis inhibitor. On the other hand, there is Patent Document 1 as a document disclosing a low molecular compound having an HGFR inhibitory action.
  • An object of the present invention is to search for and find a composition for treating esophageal cancer by suppressing abnormal cell growth, morphological change and motility enhancement through HGFR in vivo.
  • R is 1 Is a 3- to 10-membered non-aromatic heterocyclic group (provided that the ring-constituting atom always contains a nitrogen atom and has a bond from the nitrogen atom) or the formula —NR 11a R 11b (Wherein R 11a And R 11b Are the same or different and are a hydrogen atom, C 1-6 Alkyl group, C 3-6 Alkenyl group, C 3-6 Alkynyl group, C 3-10 A cycloalkyl group, C 6-10 An aryl group, a 5- to 10-membered heteroaryl group or a 4- to 10-membered non-aromatic heterocyclic group.
  • R 11a And R 11b May have a substituent selected from the following substituent group a or the following substituent group b.
  • substituent group a A halogen atom, a hydroxyl group, a mercapto group, a nitro group, a cyano group and an oxo group;
  • Substituent group b C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 A cycloalkyl group, C 6-10 Aryl group, 5- to 10-membered heteroaryl group, 3- to 10-membered non-aromatic heterocyclic group, C 1-6 Alkoxy group, C 3-6 Alkenyloxy group, C 3-6 Alkynyloxy group, C 3-10 Cycloalkoxy group, C 6-10 Aryloxy group, 5- to 10-membered heteroaryloxy group, 4- to 10-membered non-aromatic heterocyclic oxy group, C 1-6 Alkylthio group,
  • T 3 Is a hydrogen atom, C 1-6 Alkyl group, C 3-6 Alkenyl group, C 3-6 Alkynyl group, C 3-10 A cycloalkyl group, C 6-10 An aryl group, a 5- to 10-membered heteroaryl group or a 4- to 10-membered non-aromatic heterocyclic group.
  • R T1 Is a hydrogen atom or C 1-6 An alkyl group is meant. And each of the above groups may have a substituent selected from the following substituent group c.
  • R 1 May have a substituent selected from the substituent group a or the substituent group b.
  • R 2 And R 3 Means a hydrogen atom.
  • R 4 , R 5 , R 6 And R 7 Are the same or different and are a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a trifluoromethyl group, C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxy group, amino group, mono-C 1-6 Alkylamino group, di-C 1-6 Alkylamino group, formula —CO—R 12 (Wherein R 12 Is a hydrogen atom, a hydroxyl group, C 1-6 Alkyl group, C 1-6 Alkoxy group, amino group, mono-C 1-6 Alkylamino group or di-C 1-6 An alkylamino group is meant.
  • R 8 Is a hydrogen atom or C 1-6 An alkyl group is meant.
  • R 9 Is a 3- to 10-membered non-aromatic heterocyclic group (provided that the ring-constituting atom always contains a nitrogen atom and has a bond from the nitrogen atom) or the formula —NR 11a R 11b (Wherein R 11a And R 11b Means a group represented by a group represented by the same meaning as defined above. However, R 9 May have a substituent selected from the substituent group a or the substituent group b. N means an integer of 1 to 2.
  • a composition for treating esophageal cancer comprising a compound represented by the formula: [2]
  • R 1 Is a 3- to 10-membered non-aromatic heterocyclic group (however, in the atoms constituting the ring, which may have a substituent selected from the substituent group a or the substituent group b described in [1] above)
  • R 1 May have a substituent selected from the substituent group a or the substituent group b described in [1] above (Wherein a represents an integer of 1 to 4) or a substituent selected from substituent group a or substituent group b described in [1] above.
  • Good expression (Wherein b represents an integer of 1 to 3.
  • Z represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, or a formula —NR.
  • composition for treating esophageal cancer which is a group represented by: [4]
  • R 1 Is an azetidin-1-yl group which may have a substituent selected from the following substituent group d, a pyrrolidin-1-yl group which may have a substituent selected from the following substituent group d,
  • a piperidin-1-yl group optionally having a substituent selected from the following substituent group d; an azepan-1-yl group optionally having a substituent selected from the following substituent group d;
  • a piperazin-1-yl group optionally having a substituent selected from group d, a diazepan-1-yl group optionally having a substituent selected from substituent group d below, and the following substituent group a morpholin-4-yl group optionally having a substituent selected from d, a thiomorpholin-4-yl group optionally having a substituent selected from the following substituent group d, or the following substituent group
  • T 5 Is C 1-6 Alkyl group, C 3-10 Cycloalkyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, hydroxyl group, C 1-6 Alkoxy group, amino group, mono-C 1-6 Alkylamino group or di-C 1-6 An alkylamino group is meant. ), And each of the above groups is a hydroxyl group, C 1-6 Alkyl group, di-C 1-6 It may have an alkylamino group, an azetidinyl group or a pyrrolidinyl group.
  • R 1 Azetidin-1-yl group optionally having a substituent selected from the following substituent group e, pyrrolidin-1-yl group optionally having a substituent selected from the following substituent group e, A piperidin-1-yl group optionally having a substituent selected from the following substituent group e; a piperazin-1-yl group optionally having a substituent selected from the following substituent group e; A diazepan-1-yl group optionally having a substituent selected from group e or a morpholin-4-yl group optionally having a substituent selected from substituent group e below [1] The composition for esophageal cancer treatment as described.
  • Substituent group e It consists of a methyl group, an ethyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group and a piperazinyl group, each of the above groups having a hydroxyl group, a methyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group or a piperidinyl group. May be.
  • R 1 Is an azetidin-1-yl group optionally having a substituent selected from the following substituent group g, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g, and the following substituent group g
  • R 1 Azetidin-1-yl group optionally having a substituent selected from the following substituent group g-1, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g-1,
  • Substituent group g-1 An azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a dimethylaminomethyl group, a dimethylaminoethyl group, an azetidin-1-ylmethyl group, a pyrrolidin-1-ylmethyl group, and a piperidin-1-ylmethyl group, It may have a methyl group or a dimethylamino group.
  • R 1 The composition for treating esophageal cancer according to [1], wherein is an azetidin-1-yl group having a dimethylamino group, a pyrrolidin-1-yl group having a dimethylamino group, or a piperidin-1-yl group having a dimethylamino group .
  • R 1 Is an azetidin-1-yl group optionally having a substituent selected from the following substituent group g-2, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g-2, or The composition for treating esophageal cancer according to [1], which is a piperidin-1-yl group having a substituent selected from substituent group g-2.
  • [Substituent group g-2] Hydroxyl group, methoxy group, hydroxymethyl group and dimethylaminoacetoxy group.
  • R 1 [2- (dimethylamino) ethyl] piperazin-1-yl group, 4-pyrrolidin-1-ylpiperidin-1-yl group, 4-[(dimethylamino) methyl] piperidin-1-yl group, 4- Azetidin-1-ylpiperidin-1-yl group, 4- [3- (dimethylamino) azetidin-1-yl] piperidin-1-yl group, 4- (4-methylpiperazin-1-yl) piperidin-1- Yl group, 4- (1-methylpiperidin-4-yl) piperazin-1-yl group, 4- (1-methylazetidin-3-yl) piperazin-1-yl group, 4- (dimethylamino) piperidine- 1-yl group, 4- (azetidin-1-ylmethyl) piperidin-1-yl group, 4- (pyrrolidin-1-ylmethyl) piperidin-1-yl group, (3S) -3- ( (d
  • R 1 Is the formula -NR 11a R 11b (Wherein R 11a And R 11b Is R according to [1] above. 11a And R 11b Means the same.
  • R 11d Is C 1-6 Alkyl group or formula (Wherein c represents an integer of 1 to 3.
  • Z 1 Is an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group or a formula —NR Z1 -(Wherein R Z1 Is a hydrogen atom or C 1-6 An alkyl group is meant. ). ). ). ). R 11d May have a substituent selected from the substituent group a or the substituent group b described in [1] above.
  • R 11f Is C 1-6 It means an alkyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group. However, R 11f May have a substituent selected from the substituent group d described in [4] above.
  • R 1 Is the formula -NR 11g R 11h (Wherein R 11g Means a hydrogen atom or a methyl group.
  • R 11h Means an n-propyl group, n-butyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group. However, R 11h May have a substituent selected from the following substituent group f.
  • R 1 Is of the formula —N (CH 3 ) R 11i (Wherein R 11i Means n-propyl, n-butyl, pyrrolidin-3-yl or piperidin-4-yl. However, R 11i Has a substituent selected from the following substituent group h.
  • R 1 Is of the formula —N (CH 3 ) R 11j (Wherein R 11j Means 1-methylpiperidin-4-yl group or 1-ethylpiperidin-4-yl group.
  • R 1 Is a methyl (1-methylpiperidin-4-yl) amino group, (1-ethylpiperidin-4-yl) (methyl) amino group, [3- (dimethylamino) propyl] (methyl) amino group or ⁇ 1-
  • R 4 , R 5 , R 6 And R 7 are the same or different and each represents a hydrogen atom, a halogen atom or C 1-6
  • R 8 The composition for treating esophageal cancer according to any one of [1] to [13], wherein is a hydrogen atom.
  • R 9 May have a substituent selected from the substituent group a or the substituent group b described in [1] above.
  • 3-10 Mono-C which may have a cycloalkylamino group or a substituent selected from the substituent group a or the substituent group b described in [1] above 6-10
  • R 9 May have a substituent selected from the following substituent group i: 3-10 Mono-C which may have a cycloalkylamino group or a substituent selected from the following substituent group i 6-10
  • a cyclohexylamino group which may have, a cycloheptylamino group which may have a substituent selected from the substituent group i described in [19-1] above, or the substitution described in [19-1] above The composition for treating esophageal cancer according to any one of [1] to [17], which is a phenylamino group which may have a substituent selected from group i.
  • the compound represented by the general formula (I) is (1) N- [4-( ⁇ 2-[( ⁇ 4- [2- (Dimethylamino) ethyl] piperazin-1-yl ⁇ carbonyl) amino] pyridin-4-yl ⁇ oxy) -2-fluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide, (2) N- (2-Fluoro-4- ⁇ [2-( ⁇ [methyl (1-methylpiperidin-4-yl) amino] carbonyl ⁇ amino) pyridin-4-yl] oxy ⁇ phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide, (3) N- (4-Fluorophenyl) -N ′- ⁇ 2-fluoro-4-[(2- ⁇ [(4-pyrrolidin-1-ylpiperidin-1-yl) carbonyl] amino ⁇ pyridin-4
  • the compound represented by the general formula (I) is (1) N- (2-Fluoro-4- ⁇ [2-( ⁇ [4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl ⁇ amino) pyridin-4-yl] oxy ⁇ phenyl) -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide (2) N- [4-( ⁇ 2-[(azetidin-1-ylcarbonyl) amino] pyridin-4-yl ⁇ oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1- dicarboxamide (3) N- ⁇ 2,5-Difluoro-4--4-[(2- ⁇ [(3-hydroxyzetidin-1-yl) carbonyl] amino ⁇ pyridin-4-yl) oxy] phenyl ⁇ -N ′-(4- fluorphenyl)
  • a method for treating esophageal cancer comprising administering the composition for treating esophageal cancer according to any one of [1] to [21] to a patient with esophageal cancer.
  • the compound according to the present invention has an HGFR tyrosine kinase inhibitory action and inhibits the growth of human cancer cells based on HGFR activation.
  • the compound according to the present invention inhibits migration of human cancer cells.
  • the compounds according to the invention inhibit the proliferation of vascular endothelial cells via the HGF-HGFR signal.
  • the compound according to the present invention inhibits the growth of human esophageal cancer cells (Pharmacological Test Example 1). Therefore, the compound according to the present invention is useful as a composition for treating esophageal cancer.
  • the cancer type that is the target of the cancer therapeutic composition or cancer therapeutic agent is not particularly limited, and examples thereof include brain tumors (including pituitary adenoma and glioma), head and neck cancer, cervical cancer, jaw cancer, and maxilla.
  • submandibular gland cancer including tongue cancer, oral floor cancer, gingival cancer, buccal mucosa cancer, hard palate cancer), salivary gland cancer, sublingual gland cancer, parotid gland cancer, nasal cavity cancer, sinus cancer (Including maxillary sinus cancer, frontal sinus cancer, ethmoid sinus cancer, sphenoid sinus cancer), laryngeal cancer (including supraglottic cancer, glottic cancer, subglottic cancer), esophageal cancer, lung cancer (primary bronchial cancer, non-bronchial cancer) Small cell lung cancer (including lung adenocarcinoma, squamous cell carcinoma, large cell lung cancer), small cell lung cancer (including buckwheat cell type (lymphocyte-like type), intermediate cell type), mixed small cell / large cell lung cancer) Breast cancer, pancreatic cancer (including pancreatic duct cancer), gastric cancer (including Skills gastric cancer, undifferentiated gastric cancer), biliary tract cancer (including bile
  • the structural formula of a compound may represent a certain isomer for convenience, but the present invention includes all geometric isomers, optical isomers based on asymmetric carbon, and stereoisomerism that occur in the structure of the compound. Isomers such as isomers and tautomers, and mixtures of isomers, and are not limited to the description of the formula for convenience, and may be either isomer or mixture. Therefore, the compound of the present invention may have an asymmetric carbon atom in the molecule, and an optically active substance and a racemate may exist. However, the present invention is not limited to one and includes both. In addition, there are cases where crystal polymorphism may exist, but it is not limited in the same manner, and any one of the crystal forms may be a single crystal form or a mixture of crystal forms.
  • the compounds according to the present invention include anhydrides and hydrates.
  • a compound produced by metabolism, such as oxidation, reduction, hydrolysis, and conjugation, in vivo, and a compound according to the present invention undergoes metabolism such as oxidation, reduction, hydrolysis, and conjugation in vivo.
  • the compounds that produce the compounds according to the present invention are also encompassed by the claims of the present invention.
  • the “salt” includes, for example, a salt with an inorganic acid, a salt with an organic acid, a salt with an inorganic base, a salt with an organic base, a salt with an acidic or basic amino acid, etc., among which pharmacologically acceptable.
  • the salts to be prepared are preferred.
  • salts with inorganic acid include salts with hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like.
  • salts with organic acids include acetic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, lactic acid, stearic acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid. And salt.
  • salts with inorganic bases include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, aluminum salt and ammonium salt.
  • salts with an organic base include salts with diethylamine, diethanolamine, meglumine, N, N-dibenzylethylenediamine and the like.
  • Preferable examples of the salt with acidic amino acid include salts with aspartic acid, glutamic acid and the like.
  • Preferable examples of the salt with basic amino acid include salts with arginine, lysine, ornithine and the like.
  • Halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • C 1-6 alkyl group means a linear or branched alkyl group having 1 to 6 carbon atoms. Specific examples thereof include a methyl group, an ethyl group, a 1-propyl group (n -Propyl group), 2-propyl group (i-propyl group), 2-methyl-1-propyl group (i-butyl group), 2-methyl-2-propyl group (t-butyl group), 1-butyl group (N-butyl group), 2-butyl group (s-butyl group), 1-pentyl group, 2-pentyl group, 3-pentyl group, 2-methyl-1-butyl group, 3-methyl-1-butyl group 2-methyl-2-butyl group, 3-methyl-2-butyl group, 2,2-dimethyl-1-propyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 2- Methyl-1-pentyl group, 3-methyl-1-pentyl group, 4-methyl-1-pent
  • the “C 2-6 alkenyl group” means a straight or branched alkenyl group having 2 to 6 carbon atoms having one double bond.
  • an ethenyl group (vinyl Group), 1-propenyl group, 2-propenyl group (allyl group), 1-butenyl group, 2-butenyl group, 3-butenyl group, pentenyl group, hexenyl group and the like.
  • C 3-6 alkenyl group means a straight or branched alkenyl group having 3 to 6 carbon atoms having one double bond, and specific examples include a 2-propenyl group. (Allyl group), 2-butenyl group, 3-butenyl group, pentenyl group, hexenyl group and the like.
  • the “C 2-6 alkynyl group” means a straight or branched alkynyl group having 1 to 3 carbon atoms and having one triple bond. Specific examples thereof include an ethynyl group, 1- Examples include propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, pentynyl group, hexynyl group and the like.
  • C 3-6 alkynyl group means a straight or branched alkynyl group having 3 to 6 carbon atoms having one triple bond. Specific examples thereof include a 2-propynyl group, Examples thereof include 2-butynyl group, 3-butynyl group, pentynyl group, hexynyl group and the like.
  • the “C 1-6 alkylene group” means a divalent group derived by removing one arbitrary hydrogen atom from the above-defined “C 1-6 alkyl group”, and specific examples thereof include a methylene group. 1,2-ethylene group, 1,1-ethylene group, 1,3-propylene group, tetramethylene group, pentamethylene group, hexamethylene group and the like.
  • C 3-10 cycloalkyl group means a monocyclic or bicyclic saturated aliphatic hydrocarbon group having 3 to 10 carbon atoms. Specific examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group.
  • the “C 6-10 aryl group” means an aromatic hydrocarbon cyclic group having 6 to 10 carbon atoms, and specific examples thereof include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, an indenyl group. Group, azulenyl group, heptalenyl group and the like.
  • Hetero atom means nitrogen atom, oxygen atom or sulfur atom.
  • the “5- to 10-membered heteroaryl group” is an aromatic cyclic group having 5 to 10 atoms constituting the ring and containing 1 to 5 heteroatoms in the atoms constituting the ring.
  • Specific examples include furyl, thienyl, pyrrolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, isothiazolyl, furazanyl, thiadiazolyl, oxadiazolyl Group, pyridyl group, pyrazinyl group, pyridazinyl group, pyrimidinyl group, triazinyl group, purinyl group, pteridinyl group, quinolyl group, isoquinolyl group, naphthyridinyl group, quinoxalinyl group, cinnolinyl group, quinazolinyl group, phthal
  • Preferable examples of the “5- to 10-membered heteroaryl group” include furyl group, thienyl group, pyrrolyl group, imidazolyl group, thiazolyl group, pyrazolyl group, oxazolyl group, isoxazolyl group, isothiazolyl group, pyridyl group, and pyrimidinyl group. be able to.
  • “3- to 10-membered non-aromatic heterocyclic group” means (1) The number of atoms constituting the ring is 3 to 10, (2) containing 1 to 2 heteroatoms in the atoms constituting the ring; (3) The ring may contain 1 to 2 heavy bonds, (4) The ring may contain 1 to 3 carbonyl groups, sulfinyl groups or sulfonyl groups. (5) A non-aromatic cyclic group which is monocyclic or bicyclic, and when a nitrogen atom is contained in the atoms constituting the ring, a bond may be taken out from the nitrogen atom.
  • heptyl group morpholinyl group, thiomorpholinyl group, 1 1,1-dioxothiomorpholinyl group, oxiranyl group, oxetanyl group, tetrahydrofuryl group, tetrahydropyranyl group, dioxanyl group, tetrahydrothienyl group, tetrahydrothiopyranyl group, oxazolidinyl group, thiazolidinyl group and the like.
  • Suitable examples of the “3- to 10-membered non-aromatic heterocyclic group” include aziridinyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, azepanyl group, piperazinyl group, diazepanyl group, morpholinyl group, thiomorpholinyl group, 1,1 -A dioxothiomorpholinyl group, a tetrahydrofuryl group and a tetrahydropyranyl group can be mentioned.
  • “4- to 10-membered non-aromatic heterocyclic group” means (1) The number of atoms constituting the ring is 4 to 10, (2) containing 1 to 2 heteroatoms in the atoms constituting the ring; (3) The ring may contain 1 to 2 double bonds, (4) The ring may contain 1 to 3 carbonyl groups, sulfinyl groups or sulfonyl groups. (5) A non-aromatic cyclic group which is monocyclic or bicyclic, and when a nitrogen atom is contained in the atoms constituting the ring, a bond may be taken out from the nitrogen atom.
  • azetidinyl group pyrrolidinyl group, piperidinyl group, azepanyl group, azocanyl group, piperazinyl group, diazepanyl group, diazocanyl group, diazabicyclo [2.2.1] heptyl group, morpholinyl group, thiomorpholinyl group, 1,1- Examples thereof include a dioxothiomorpholinyl group, an oxetanyl group, a tetrahydrofuryl group, a tetrahydropyranyl group, a dioxanyl group, a tetrahydrothienyl group, a tetrahydrothiopyranyl group, an oxazolidinyl group, and a thiazolidinyl group.
  • Preferable examples of the “4- to 10-membered non-aromatic heterocyclic group” include azetidinyl group, pyrrolidinyl group, piperidinyl group, azepanyl group, piperazinyl group, diazepanyl group, morpholinyl group, thiomorpholinyl group, 1,1-dioxo Examples thereof include a thiomorpholinyl group, a tetrahydrofuryl group, and a tetrahydropyranyl group.
  • C 3-10 cycloalkyl C 1-6 alkyl group any hydrogen atom in the definition of "C 1-6 alkyl group” was replaced with the above defined “C 3-10 cycloalkyl group” group
  • Specific examples include cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, cyclooctylmethyl group, cyclononylmethyl group, cyclodecylmethyl group, bicyclo [2 2.1] heptylmethyl group (norbornylmethyl group), bicyclo [4.4.0] decylmethyl group (decalylmethyl group), and the like.
  • C 6-10 aryl C 1-6 alkyl group means a group in which any hydrogen atom in the above-defined “C 1-6 alkyl group” is substituted with the above-defined “C 6-10 aryl group” Specific examples include a benzyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, phenethyl group, 1-naphthylethyl group, 2-naphthylethyl group and the like.
  • the “5- to 10-membered heteroaryl C 1-6 alkyl group” is a group in which any hydrogen atom in the above-defined “C 1-6 alkyl group” is substituted with the above-defined “5- to 10-membered heteroaryl group”
  • Specific examples include furylmethyl, thienylmethyl, pyrrolylmethyl, imidazolylmethyl, triazolylmethyl, tetrazolylmethyl, thiazolylmethyl, pyrazolylmethyl, oxazolylmethyl, iso Oxazolylmethyl, isothiazolylmethyl, furazanylmethyl, thiadiazolylmethyl, oxadiazolylmethyl, pyridylmethyl, pyrazinylmethyl, pyridazinylmethyl, pyrimidinylmethyl, triazinylmethyl , Furylethyl group, thienylethyl group, pyrrolylethyl group, imidazolylethyl group, tria
  • “5- to 10-membered heteroaryl C 1-6 alkyl group” include furylmethyl group, thienylmethyl group, pyrrolylmethyl group, imidazolylmethyl group, thiazolylmethyl group, pyrazolylmethyl group, oxazolylmethyl group, iso Oxazolylmethyl, isothiazolylmethyl, pyridylmethyl, pyrimidinylmethyl, furylethyl, thienylethyl, pyrrolylethyl, imidazolylethyl, thiazolylethyl, pyrazolylethyl, oxazolylethyl, isoxa Examples thereof include a zolylethyl group, an isothiazolylethyl group, a pyridylethyl group, and a pyrimidinylethyl group.
  • “3- to 10-membered non-aromatic heterocyclic C 1-6 alkyl group” means any hydrogen atom in the above-defined “C 1-6 alkyl group” as defined in the above-mentioned “3- to 10-membered non-aromatic heterocyclic ring”.
  • a group substituted by the formula group includes aziridinylmethyl group, azetidinylmethyl group, pyrrolidinylmethyl group, piperidinylmethyl group, azepanylmethyl group, azocanylmethyl group, piperazinylmethyl Group, diazepanylmethyl group, diazocanylmethyl group, morpholinylmethyl group, thiomorpholinylmethyl group, 1,1-dioxothiomorpholinylmethyl group, oxiranylmethyl group, oxetanylmethyl group Tetrahydrofurylmethyl group, tetrahydropyranylmethyl group, dioxanylmethyl group, tetrahydrothienylmethyl group, tetrahydrothiopyranylmethyl group, oxa Lydinylmethyl group, thiazolidinylmethyl group, aziridinylethyl group, azetidinylethyl group, pyrrolidinylethyl group, piperid
  • “3 to 10-membered non-aromatic heterocyclic C 1-6 alkyl group” include azetidinylmethyl group, pyrrolidinylmethyl group, piperidinylmethyl group, azepanylmethyl group, piperazinylmethyl group , Diazepanylmethyl group, morpholinylmethyl group, thiomorpholinylmethyl group, tetrahydrofurylmethyl group, azetidinylethyl group, pyrrolidinylethyl group, piperidinylethyl group, azepanylethyl group, piperazinyl Examples thereof include an ethyl group, a diazepanylethyl group, a morpholinylethyl group, a thiomorpholinylethyl group, and a tetrahydrofurylethyl group.
  • the “C 1-6 alkoxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 1-6 alkyl group”, and specifically includes a methoxy group, an ethoxy group, 1- Propoxy group (n-propoxy group), 2-propoxy group (i-propoxy group), 2-methyl-1-propoxy group (i-butoxy group), 2-methyl-2-propoxy group (t-butoxy group), 1-butoxy group (n-butoxy group), 2-butoxy group (s-butoxy group), 1-pentyloxy group, 2-pentyloxy group, 3-pentyloxy group, 2-methyl-1-butoxy group, 3 -Methyl-1-butoxy group, 2-methyl-2-butoxy group, 3-methyl-2-butoxy group, 2,2-dimethyl-1-propoxy group, 1-hexyloxy group, 2-hexyloxy group, 3 -Hexyloxy 2-methyl-1-pentyloxy group, 3-methyl-1-pentyloxy group, 4-methyl-1-penty
  • C 1-6 alkylthio group means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 1-6 alkyl group”. Specific examples thereof include a methylthio group, an ethylthio group, a 1- Propylthio group (n-propylthio group), 2-propylthio group (i-propylthio group), 2-methyl-1-propylthio group (i-butylthio group), 2-methyl-2-propylthio group (t-butylthio group), 1-butylthio group (n-butylthio group), 2-butylthio group (s-butylthio group), 1-pentylthio group, 2-pentylthio group, 3-pentylthio group, 2-methyl-1-butylthio group, 3-methyl- 1-butylthio group, 2-methyl-2-butylthio group, 3-methyl-2-butylthio group, 2,2-dimethyl-1-propy
  • the “C 3-6 alkenyloxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 3-6 alkenyl group”. Specifically, for example, a 2-propenyloxy group (Allyloxy group), 2-butenyloxy group, 3-butenyloxy group, pentenyloxy group, hexenyloxy group and the like.
  • the “C 3-6 alkenylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 3-6 alkenyl group”.
  • a specific example includes 2- Examples include propenylthio group (allylthio group), 2-butenylthio group, 3-butenylthio group, pentenylthio group, hexenylthio group and the like.
  • C 3-6 alkynyloxy group means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 3-6 alkynyl group”. Specific examples include a 2-propynyloxy group, -Butynyloxy group, 3-butynyloxy group, pentynyloxy group, hexynyloxy group and the like.
  • C 3-6 alkynylthio group means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 3-6 alkynyl group”. Specific examples include a 2-propynylthio group, 2 -Butynylthio group, 3-butynylthio group, pentynylthio group, hexynylthio group and the like.
  • C 3-10 cycloalkoxy group means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 3-10 cycloalkyl group”. Specific examples thereof include a cyclopropoxy group, cyclobutoxy group, and the like. Group, cyclopentyloxy group, cyclohexyloxy group, cycloheptyloxy group, cyclooctyloxy group and the like.
  • the “C 3-10 cycloalkylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 3-10 cycloalkyl group”.
  • Specific examples include a cyclopropylthio group, a cyclopropyl group, Examples thereof include a butylthio group, a cyclopentylthio group, a cyclohexylthio group, a cycloheptylthio group, and a cyclooctylthio group.
  • the “C 6-10 aryloxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 6-10 aryl group”. Specific examples thereof include a phenoxy group and a 1-naphthoxy group. 2-naphthoxy group, indenyloxy group, azulenyloxy group, heptalenyloxy group and the like.
  • the “C 6-10 arylthio group” means a group having a sulfur atom bonded to the end of the above-defined “C 6-10 aryl group”. Specific examples thereof include a phenylthio group, a 1-naphthylthio group, A 2-naphthylthio group, an indenylthio group, an azulenylthio group, a heptalenylthio group and the like can be mentioned.
  • the “5- to 10-membered heteroaryloxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “5- to 10-membered heteroaryl group”.
  • Specific examples include a furyloxy group, thienyl.
  • the “5- to 10-membered heteroarylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “5- to 10-membered heteroaryl group”.
  • Specific examples include a furylthio group and a thienylthio group.
  • Pyrrolylthio group imidazolylthio group, triazolylthio group, thiazolylthio group, pyrazolylthio group, oxazolylthio group, isoxazolylthio group, isothiazolylthio group, furazanylthio group, thiadiazolylthio group, oxadiazolylthio group, pyridylthio group , Pyrazinylthio group, pyridazinylthio group, pyrimidinylthio group, triazinylthio group and the like.
  • “4- to 10-membered non-aromatic heterocyclic group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “4- to 10-membered non-aromatic heterocyclic group”.
  • the “4- to 10-membered non-aromatic heterocyclic thio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “4- to 10-membered non-aromatic heterocyclic group”.
  • “Mono-C 1-6 alkylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “C 1-6 alkyl group”. Specific examples include methylamino Group, ethylamino group, 1-propylamino group (n-propylamino group), 2-propylamino group (i-propylamino group), 2-methyl-1-propylamino group (i-butylamino group), 2 -Methyl-2-propylamino group (t-butylamino group), 1-butylamino group (n-butylamino group), 2-butylamino group (s-butylamino group), 1-pentylamino group, 2- Pentylamino group, 3-pentylamino group, 2-methyl-1-butylamino group, 3-methyl-1-butylamino group, 2-methyl-2-butylamino group, 3-methyl-2-butylamino group, 2,2-jime 1-he
  • “Mono-C 3-10 cycloalkylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “C 3-10 cycloalkyl group”. Examples thereof include a cyclopropylamino group, a cyclobutylamino group, a cyclopentylamino group, a cyclohexylamino group, a cycloheptylamino group, and a cyclooctylamino group.
  • “Mono-C 6-10 arylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “C 6-10 aryl group”. Specific examples include phenylamino Group, 1-naphthylamino group, 2-naphthylamino group, indenylamino group, azulenylamino group, heptalenylamino group and the like.
  • “Mono-5 to 10-membered heteroarylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “5 to 10-membered heteroaryl group”.
  • Furylamino group, thienylamino group, pyrrolylamino group, imidazolylamino group, triazolylamino group, tetrazolylamino group, thiazolylamino group, pyrazolylamino group, oxazolylamino group, isoxazolylamino group, isothiazo Examples include a tolylamino group, a furazanylamino group, a thiadiazolylamino group, an oxadiazolylamino group, a pyridylamino group, a pyrazinylamino group, a pyridazinylamino group, a pyrimidinylamino group, and a triazinylamino group
  • Suitable examples of the “mono-5 to 10-membered heteroarylamino group” include a furylamino group, a thienylamino group, a pyrrolylamino group, an imidazolylamino group, a thiazolylamino group, a pyrazolylamino group, an oxazolylamino group, and an isoxazolyl group. Examples thereof include a ruamino group, an isothiazolylamino group, a pyridylamino group, and a pyrimidinylamino group.
  • “Mono-4 to 10-membered non-aromatic heterocyclic amino group” means a group in which one hydrogen atom in the amino group is substituted with the above-mentioned “4 to 10-membered non-aromatic heterocyclic group” Specific examples include azetidinylamino group, pyrrolidinylamino group, piperidinylamino group, azepanylamino group, azocanylamino group, piperazinylamino group, diazepanylamino group, diazocanylamino group, Morpholinylamino group, thiomorpholinylamino group, 1,1-dioxothiomorpholinylamino group, oxetanylamino group, tetrahydrofurylamino group, tetrahydropyranylamino group, tetrahydrothienylamino group, tetrahydrothiopyranyl An amino group etc. are mention
  • Suitable examples of the “mono-4 to 10-membered non-aromatic heterocyclic amino group” include pyrrolidinylamino group, piperidinylamino group, azepanylamino group, piperazinylamino group, diazepanylamino group, Examples thereof include a morpholinylamino group, a thiomorpholinylamino group, and a tetrahydrofurylamino group.
  • the "di -C 1-6 alkylamino group”, the two hydrogen atoms in an amino group, each same or different, means a group obtained by substituting the above-defined "C 1-6 alkyl group", specifically Examples include N, N-dimethylamino group, N, N-diethylamino group, N, N-di-n-propylamino group, N, N-di-i-propylamino group, N, N-di-n.
  • R 1 is a 3- to 10-membered non-aromatic heterocyclic group (provided that a nitrogen atom is necessarily contained in the atoms constituting the ring and a bond is drawn from the nitrogen atom) or a formula — NR 11a R 11b (wherein R 11a and R 11b are the same or different and each represents a hydrogen atom, a C 1-6 alkyl group, a C 3-6 alkenyl group, a C 3-6 alkynyl group, a C 3-10 cycloalkyl group) Group, C 6-10 aryl group, 5- to 10-membered heteroaryl group or 4- to 10-membered non-aromatic heterocyclic group, provided that R 11a and R 11b are the following substituent group a or the following substituents Which may have a substituent selected from group b).
  • R 1 may have a substituent selected from the following substituent group a or the following substituent group b.
  • Suitable examples of R 1 include the formula (Wherein a represents an integer of 1 to 4), a group represented by the formula (Wherein b represents an integer of 1 to 3.
  • R Z represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, or a formula —NR Z — (wherein R Z represents a hydrogen atom or C 1- 6 means an alkyl group.)
  • R Z represents a hydrogen atom or C 1- 6 means an alkyl group.
  • the groups represented by the above formulas (II) and (III) are the following substituent group a or Which may have a substituent selected from the substituent group b) or a formula —NR 11c R 11d (wherein R 11c represents a hydrogen atom or a C 1-6 alkyl group.
  • R 11d represents C 1-6 alkyl group or formula (Wherein c is an integer of 1 to 3.
  • Z 1 is an oxygen atom, sulfur atom, carbonyl group, sulfonyl group or formula —NR Z1 — (wherein R Z1 is a hydrogen atom or C 1 Means a -6 alkyl group.) Means a group represented by). However, R 11d may have a substituent selected from the following substituent group a or the following substituent group b. ).
  • R 1 More preferred examples of R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group, azepan-1-yl group, piperazin-1-yl group, diazepan-1-yl A group, morpholin-4-yl group, thiomorpholin-4-yl group, 1,1-dioxothiomorpholin-4-yl group or a formula —NR 11e R 11f (wherein R 11e is a hydrogen atom or C 1 .R 11f meaning -6 alkyl group means a C 1-6 alkyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group However, R 11f may have a substituent selected from the following substituent group d.
  • R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group, piperazin-1-yl group, diazepan-1-yl group, morpholin-4-yl A group (wherein each group may have a substituent selected from the following substituent group e) or a formula —NR 11g R 11h (wherein R 11g represents a hydrogen atom or a methyl group) R 11h represents an n-propyl group, n-butyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group, provided that R 11h may have a substituent selected from the following substituent group f)).
  • R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group or piperazin-1-yl group (provided that azetidin-1-yl group has the following substituents)
  • the pyrrolidin-1-yl group, the piperidin-1-yl group and the piperazin-1-yl group may have a substituent selected from the following substituent group g.
  • R 11i represents an n-propyl group, an n-butyl group, a pyrrolidin-3-yl group, or a piperidin-4-yl group, provided that R 11i has a substituent selected from the following substituent group h).
  • R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group or piperazin-1-yl group (provided that the azetidin-1-yl group is substituted by
  • the pyrrolidin-1-yl group, piperidin-1-yl group and piperazin-1-yl group may be selected from the following substituent group g-1 Azetidin-1-yl group having a dimethylamino group, pyrrolidin-1-yl group having a dimethylamino group, piperidin-1-yl group having a dimethylamino group, formula —N (CH 3 ) R 11j (wherein, R 11j is meant 1-methylpiperidin-4-yl group or 1-ethyl-piperidin-4-yl group.), a group represented by selected from the following substituent group g-2 An azetidin-1-yl group which may have a substituent, a pyrroli
  • R 1 include [2- (dimethylamino) ethyl] piperazin-1-yl group, 4-pyrrolidin-1-ylpiperidin-1-yl group, 4-[(dimethylamino) methyl ] Piperidin-1-yl group, 4-azetidin-1-yl piperidin-1-yl group, 4- [3- (dimethylamino) azetidin-1-yl] piperidin-1-yl group, 4- (4-methyl Piperazin-1-yl) piperidin-1-yl group, 4- (1-methylpiperidin-4-yl) piperazin-1-yl group, 4- (1-methylazetidin-3-yl) piperazin-1-yl A 4- (dimethylamino) piperidin-1-yl group, a 4- (azetidin-1-ylmethyl) piperidin-1-yl group, a 4- (pyrrolidin-1-ylmethyl) piperidin-1-yl group, 3
  • the substituent group a means a group consisting of a halogen atom, a hydroxyl group, a mercapto group, a nitro group, a cyano group, and an oxo group.
  • Substituent group b includes a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-10 cycloalkyl group, a C 6-10 aryl group, a 5-10 membered heteroaryl group, 3- to 10-membered non-aromatic heterocyclic group, C 1-6 alkoxy group, C 3-6 alkenyloxy group, C 3-6 alkynyloxy group, C 3-10 cycloalkoxy group, C 6-10 aryloxy group 5- to 10-membered heteroaryloxy group, 4- to 10-membered non-aromatic heterocyclic oxy group, C 1-6 alkylthio group, C 3-6 alkenylthio group, C 3-6 alkynylthio group, C 3-10 cyclo An alkylthio group, a C 6-10 arylthio group, a 5- to 10-membered heteroary
  • T 2 is a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula —C ( ⁇ O) —O—, a group represented by the formula —O—C ( ⁇ O) —, or a formula —SO 2 —.
  • T 3 is a hydrogen atom, a C 1-6 alkyl group, a C 3-6 alkenyl group, a C 3-6 alkynyl group, a C 3-10 cycloalkyl group, a C 6-10 aryl group, or a 5-10 membered heteroaryl group Or a 4- to 10-membered non-aromatic heterocyclic group.
  • R T1 means a hydrogen atom or a C 1-6 alkyl group.
  • Substituent group c includes halogen atom, hydroxyl group, mercapto group, nitro group, cyano group, oxo group, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-10 cycloalkyl Group, C 6-10 aryl group, 5-10 membered heteroaryl group, 3-10 membered non-aromatic heterocyclic group, C 1-6 alkoxy group, C 1-6 alkylthio group, mono-C 1-6 alkyl It means a group consisting of an amino group and a di-C 1-6 alkylamino group.
  • Substituent group d includes a halogen atom, a hydroxyl group, a mercapto group, a cyano group, a formyl group, an oxo group, a C 1-6 alkyl group, a C 3-10 cycloalkyl group, a C 1-6 alkoxy group, an amino group, a mono- A C 1-6 alkylamino group, a di-C 1-6 alkylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a diazepanyl group, and a formula —T 4 -T 5 (wherein T 4 is a carbonyl group) Or a sulfonyl group is meant.
  • T 5 is a C 1-6 alkyl group, a C 3-10 cycloalkyl group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a hydroxyl group, a C 1-6 alkoxy group, an amino group, a mono-C 1-6 alkylamino group or Means a di-C 1-6 alkylamino group; ) Represents a group consisting of groups represented by However, each group described in the substituent group d may have a hydroxyl group, a C 1-6 alkyl group, a di-C 1-6 alkylamino group, an azetidinyl group, or a pyrrolidinyl group.
  • the substituent group e means a methyl group, an ethyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, and a piperazinyl group.
  • each group described in the substituent group e may have a hydroxyl group, a methyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, or a piperidinyl group.
  • the substituent group f means a methyl group, an ethyl group, an n-propyl group, an acetyl group, a dimethylamino group, a diethylamino group, an azetidinyl group, a pyrrolidinyl group, and a piperazinyl group.
  • each group described in the substituent group f may have a methyl group or a dimethylamino group.
  • Substituent group g includes dimethylamino group, azetidinyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group, dimethylaminomethyl group, dimethylaminoethyl group, azetidin-1-ylmethyl group, pyrrolidin-1-ylmethyl group and piperidin-1- It means an ylmethyl group.
  • each group described in the substituent group g may have a methyl group or a dimethylamino group.
  • Substituent group g-1 includes azetidinyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group, dimethylaminomethyl group, dimethylaminoethyl group, azetidin-1-ylmethyl group, pyrrolidin-1-ylmethyl group and piperidin-1-ylmethyl group Means. However, each group described in the substituent group g-1 may have a methyl group or a dimethylamino group.
  • Substituent group g-2 means a hydroxyl group, a methoxy group, a hydroxymethyl group, and a dimethylaminoacetoxy group.
  • the substituent group h means a dimethylamino group, a diethylamino group, a dimethylaminoethyl group, a dimethylaminopropyl group and a 1-methylazetidin-3-yl group.
  • R 2 and R 3 represent a hydrogen atom.
  • R 4 , R 5 , R 6 and R 7 are the same or different and are a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a trifluoromethyl group, a C 1-6 alkyl group, a C 2-6 alkenyl group, C 2 -6 alkynyl group, C 1-6 alkoxy group, amino group, mono-C 1-6 alkylamino group, di-C 1-6 alkylamino group, formula —CO—R 12 wherein R 12 is hydrogen An atom, a hydroxyl group, a C 1-6 alkyl group, a C 1-6 alkoxy group, an amino group, a mono-C 1-6 alkylamino group or a di-C 1-6 alkylamino group).
  • R 4 , R 5 , R 6 and R 7 include a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group or a trifluoromethyl group. More preferred examples of R 4 , R 5 , R 6 and R 7 include a hydrogen atom, a halogen atom or a C 1-6 alkyl group. More preferred examples of R 4 , R 5 , R 6 and R 7 include a hydrogen atom, a fluorine atom, a chlorine atom or a methyl group.
  • R 4 , R 5 , R 6 and R 7 are 1) when all are hydrogen atoms, 2) when all are substituents other than hydrogen atoms, 3) when they are substituents other than hydrogen atoms or hydrogen atoms Any of them may be used, but preferably 2 to 4 of R 4 , R 5 , R 6 and R 7 are hydrogen atoms.
  • the formula As preferable examples of the group represented by the formula: A group or formula represented by And a group represented by
  • R 8 represents a hydrogen atom or a C 1-6 alkyl group.
  • a preferred example of R 8 is a hydrogen atom.
  • R 9 represents a 3- to 10-membered non-aromatic heterocyclic group (provided that a nitrogen atom is necessarily contained in the atoms constituting the ring and a bond is drawn from the nitrogen atom) or a formula — A group represented by a group represented by NR 11a R 11b (wherein R 11a and R 11b have the same meanings as defined above). However, R 9 may have a substituent selected from the substituent group a or the substituent group b.
  • R 9 include mono-C 1-6 alkylamino group, mono-C 3-10 cycloalkylamino group, mono-C 6-10 arylamino group, mono-5-10 membered heteroarylamino Group or a mono-4 to 10-membered non-aromatic heterocyclic amino group (provided that R 9 may have a substituent selected from the substituent group a or the substituent group b).
  • R 9 is mono- -C 3-10 cycloalkylamino or mono -C 6-10 arylamino group (wherein, R 9 is the above-mentioned substituent group a or the above-mentioned substituent group It may have a substituent selected from b).
  • R 9 include a mono-C 3-10 cycloalkylamino group or a mono-C 6-10 arylamino group (wherein R 9 is a substituent selected from the following substituent group i) May be included.)
  • [Substituent group i] A halogen atom, a trifluoromethyl group, a cyano group, a C 1-6 alkyl group and a C 1-6 alkoxy group;
  • Particularly preferred examples of R 9 include a cyclopentylamino group, a cyclohexylamino group, a cycloheptylamino group, and a phenylamino group (provided that R 9 has a substituent selected from the above substituent group i). May be.
  • a most preferred example of R 9 is a phenylamino group which may have a substituent selected from the above substituent group i.
  • n means an integer of 1 to 2.
  • a preferred example of n is 1.
  • each aspect of the R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X and n in the compound is selected. And compounds in which they are arbitrarily combined.
  • More preferred specific examples of the compound represented by the general formula (I) include the compounds shown below.
  • the phrase “may have a substituent selected from the substituent group” means that it may have 1 to 3 substituents arbitrarily selected from the substituents described in the substituent group. Means good.
  • the compound according to the present invention can be produced based on the description in International Publication No. 2007/023768.
  • Pharmacological Test Example 1 Inhibitory action on human esophageal cancer cell proliferation
  • Human esophageal cancer cells (OE19, OE21 and OE33) were purchased from Dainippon Sumitomo Pharma Co., Ltd. OE19, OE21 or OE33 was suspended in RPMI 1640 medium (purchased from Sigma) containing 10% FBS. The cell suspension (2 ⁇ 10 4 cells / ml) was added to a 96-well plate for cell culture (purchased from FALCON, product number 353075) at 0.1 ml / well in a 5% CO 2 incubator (37 ° C.). Incubated overnight.
  • a test substance diluted with RPMI 1640 medium containing 10% FBS was added to each well, and further cultured in a 5% CO 2 incubator (37 ° C.) for 3 days.
  • 10 ⁇ l of Cell Counting Kit-8 purchased from DOJINDO, product number 343-07623 was added to each well and incubated in a 5% CO 2 incubator (37 ° C.) for about 2 hours.
  • the measurement wavelength was 450 nm and the control wavelength was 660 nm, and the absorbance of each well was measured using a plate reader MTP-500 (manufactured by Corona Electric Co., Ltd.).
  • the compound according to the present invention has an excellent HGFR inhibitory action and is useful as a composition for treating esophageal cancer.

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Abstract

Disclosed is a compound represented by the general formula (I) shown below, a salt of the compound, or a hydrate of the compound or the salt, which is useful in a composition for the treatment of esophageal cancer. [Formula] (I) wherein R1 represents a 3- to 10-membered non-aromatic heterocyclic group or the like; R2 and R3 independently represent a hydrogen atom; R4, R5, R6 and R7 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group or the like; R8 represents a hydrogen atom or the like; R9 represents a 3- to 10-membered non-aromatic heterocyclic group or the like; n represents an integer of 1 or 2; and X represents a group represented by the formula: -CH= or a nitrogen atom.

Description

食道癌治療用組成物Esophageal cancer treatment composition
　本発明は、肝細胞増殖因子受容体阻害作用、抗腫瘍作用、血管新生阻害作用、癌転移抑制作用などを有する新規なピリジン誘導体およびピリミジン誘導体もしくはその塩またはそれらの水和物を含有する食道癌治療用組成物に関する。 The present invention relates to esophageal cancer containing novel pyridine derivatives and pyrimidine derivatives or salts thereof or hydrates thereof having hepatocyte growth factor receptor inhibitory action, antitumor action, angiogenesis inhibitory action, cancer metastasis inhibitory action, etc. It relates to a therapeutic composition.
　膵臓癌、胃癌、大腸癌、乳癌、前立腺癌、肺癌、腎癌、脳腫瘍、卵巣癌、食道癌など種々の腫瘍において、肝細胞増殖因子受容体（Ｈｅｐａｔｏｃｙｔｅ　ｇｒｏｗｔｈ　ｆａｃｔｏｒ　ｒｅｃｅｐｔｏｒ；以下、「ＨＧＦＲ」と略す）の過剰発現が報告されている（非特許文献１および５）。これら腫瘍細胞に発現したＨＧＦＲは、恒常的に、または肝細胞増殖因子（Ｈｅｐａｔｏｃｙｔｅ　ｇｒｏｗｔｈ　ｆａｃｔｏｒ；以下、「ＨＧＦ」と略す）に刺激されて、細胞内領域のチロシンキナーゼ自己リン酸化を起こすため、癌悪性化（異常増殖、浸潤または転移能亢進）に関与しているものと考えられている。
　また、ＨＧＦＲは、血管内皮細胞にも発現しており、ＨＧＦがＨＧＦＲを刺激し、血管内皮細胞の増殖および遊走を促進するため、腫瘍血管新生に関与することが報告されている（非特許文献２）。
　さらに、ＨＧＦ拮抗ペプチドであるＮＫ４が、ＨＧＦ－ＨＧＦＲシグナルを遮断することにより、癌細胞の浸潤を抑制し、腫瘍血管新生を阻害することが報告されている（非特許文献３、４）。
　したがって、ＨＧＦＲ阻害作用を有する化合物は、抗腫瘍剤、血管新生阻害剤または癌転移抑制剤として有用であることが期待される。
　一方、ＨＧＦＲ阻害作用を有する低分子化合物を開示した文献として、特許文献１がある。 Hepatocyte growth factor receptor (hereinafter abbreviated as “HGFR”) in various tumors such as pancreatic cancer, stomach cancer, colon cancer, breast cancer, prostate cancer, lung cancer, kidney cancer, brain tumor, ovarian cancer, and esophageal cancer. ) Has been reported (Non-patent Documents 1 and 5). HGFR expressed in these tumor cells is stimulated constitutively or by hepatocyte growth factor (hereinafter abbreviated as “HGF”) to cause tyrosine kinase autophosphorylation in the intracellular region. It is thought to be involved in malignant transformation (abnormal growth, invasion or increased metastatic potential).
In addition, HGFR is also expressed in vascular endothelial cells, and HGF stimulates HGFR and promotes proliferation and migration of vascular endothelial cells, and thus has been reported to be involved in tumor angiogenesis (Non-Patent Document). 2).
Furthermore, it has been reported that NK4, which is an HGF antagonist peptide, inhibits cancer cell invasion and inhibits tumor angiogenesis by blocking the HGF-HGFR signal (Non-Patent Documents 3 and 4).
Therefore, a compound having an HGFR inhibitory action is expected to be useful as an antitumor agent, an angiogenesis inhibitor or a cancer metastasis inhibitor.
On the other hand, there is Patent Document 1 as a document disclosing a low molecular compound having an HGFR inhibitory action.
国際公開第２００７／０２３７６８号パンフレットInternational Publication No. 2007/023768 Pamphlet
　本発明の目的は、生体内におけるＨＧＦＲを介した細胞の異常増殖、形態変化および運動能亢進を抑制することによる食道癌治療用組成物を探索し見出すことにある。 An object of the present invention is to search for and find a composition for treating esophageal cancer by suppressing abnormal cell growth, morphological change and motility enhancement through HGFR in vivo.
　本発明者らは、上記事情に鑑み鋭意研究を重ねた結果、下記一般式（Ｉ）で表される新規なピリジン誘導およびピリミジン誘導体もしくはその塩またはそれらの水和物が優れたＨＧＦＲ阻害作用を有し、かつ抗食道癌治療作用を示すことを見出し、本発明を完成した。 As a result of intensive studies in view of the above circumstances, the present inventors have found that a novel pyridine derivative represented by the following general formula (I) and a pyrimidine derivative or a salt thereof or a hydrate thereof have an excellent HGFR inhibitory action. And the present invention was completed.
　すなわち、本発明は以下の［１］～［２４］を提供する。
［１］一般式
Figure JPOXMLDOC01-appb-C000005
 　（式中、Ｒ１は、３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）または式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、同一または異なって、水素原子、Ｃ１－６アルキル基、Ｃ３－６アルケニル基、Ｃ３－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員へテロアリール基または４～１０員非芳香族ヘテロ環式基を意味する。ただし、Ｒ１１ａおよびＲ１１ｂは、下記置換基群ａまたは下記置換基群ｂから選ばれる置換基を有していてもよい。
［置換基群ａ］
ハロゲン原子、水酸基、メルカプト基、ニトロ基、シアノ基およびオキソ基。
［置換基群ｂ］
Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基、３～１０員非芳香族ヘテロ環式基、Ｃ１－６アルコキシ基、Ｃ３－６アルケニルオキシ基、Ｃ３－６アルキニルオキシ基、Ｃ３－１０シクロアルコキシ基、Ｃ６－１０アリールオキシ基、５～１０員ヘテロアリールオキシ基、４～１０員非芳香族ヘテロ環オキシ基、Ｃ１－６アルキルチオ基、Ｃ３－６アルケニルチオ基、Ｃ３－６アルキニルチオ基、Ｃ３－１０シクロアルキルチオ基、Ｃ６－１０アリールチオ基、５～１０員ヘテロアリールチオ基、４～１０員非芳香族ヘテロ環チオ基および式－Ｔ１－Ｔ２－Ｔ３
　(式中、Ｔ１は、単結合またはＣ１－６アルキレン基を意味する。
　Ｔ２は、カルボニル基、スルフィニル基、スルホニル基、式－Ｃ（＝Ｏ）－Ｏ－で表される基、式－Ｏ－Ｃ（＝Ｏ）－で表される基、式－ＳＯ２－Ｏ－で表される基、式－Ｏ－ＳＯ２－で表される基、式－ＮＲＴ１－で表される基、式－Ｃ（＝Ｏ）－ＮＲＴ１－で表される基、式－ＮＲＴ１－Ｃ（＝Ｏ）－で表される基、式－ＳＯ２－ＮＲＴ１－で表される基または式－ＮＲＴ１－ＳＯ２－で表される基を意味する。
　Ｔ３は、水素原子、Ｃ１－６アルキル基、Ｃ３－６アルケニル基、Ｃ３－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基または４～１０員非芳香族ヘテロ環式基を意味する。
　ＲＴ１は、水素原子またはＣ１－６アルキル基を意味する。）で表される基からなり、上記各基は、下記置換基群ｃから選ばれる置換基を有していてもよい。
［置換基群ｃ］
ハロゲン原子、水酸基、メルカプト基、ニトロ基、シアノ基、オキソ基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基、３～１０員非芳香族ヘテロ環式基、Ｃ１－６アルコキシ基、Ｃ１－６アルキルチオ基、モノ－Ｃ１－６アルキルアミノ基およびジ－Ｃ１－６アルキルアミノ基。）で表される基を意味する。
　ただし、Ｒ１は、上記置換基群ａまたは上記置換基群ｂから選ばれる置換基を有していてもよい。
　Ｒ２およびＲ３は、水素原子を意味する。
　Ｒ４、Ｒ５、Ｒ６およびＲ７は、同一または異なって、水素原子、ハロゲン原子、水酸基、シアノ基、トリフルオロメチル基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基、ジ－Ｃ１－６アルキルアミノ基、式－ＣＯ－Ｒ１２（式中、Ｒ１２は、水素原子、水酸基、Ｃ１－６アルキル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基またはジ－Ｃ１－６アルキルアミノ基を意味する。）で表される基を意味する。
　Ｒ８は、水素原子またはＣ１－６アルキル基を意味する。
　Ｒ９は、３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）または式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、上記定義と同意義を意味する）で表される基で表される基を意味する。
　ただし、Ｒ９は、上記置換基群ａまたは上記置換基群ｂから選ばれる置換基を有していてもよい。
　ｎは、１ないし２の整数を意味する。
　Ｘは、式－Ｃ（Ｒ１０）＝（式中、Ｒ１０は、水素原子、ハロゲン原子、シアノ基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、式－ＣＯ－Ｒ１２（式中、Ｒ１２は、上記定義と同意義を意味する。）で表される基を意味する。）で表される基または窒素原子を意味する。）
で表される化合物もしくはその塩またはそれらの水和物を含有する食道癌治療用組成物。
［２］　Ｒ１が、上記［１］に記載の置換基群ａまたは置換基群ｂから選ばれる置換基を有していてもよい３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）である［１］記載の食道癌治療用組成物。
［３］　Ｒ１が、上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよい式
Figure JPOXMLDOC01-appb-C000006
 （式中、ａは、１ないし４の整数を意味する。）で表される基または上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよい式
Figure JPOXMLDOC01-appb-C000007
 （式中、ｂは、１ないし３の整数を意味する。Ｚは、酸素原子、硫黄原子、カルボニル基、スルホニル基または式－ＮＲＺ－（式中、ＲＺは、水素原子またはＣ１－６アルキル基を意味する。）で表される基を意味する。）で表される基である［１］記載の食道癌治療用組成物。
［４］　Ｒ１が、下記置換基群ｄから選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいピロリジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいピペリジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいアゼパン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいピペラジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいジアゼパン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいモルホリン－４－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいチオモルホリン－４－イル基または下記置換基群ｄから選ばれる置換基を有していてもよい１，１－ジオキソチオモルホリン－４－イル基である［１］記載の食道癌治療用組成物。
［置換基群ｄ］
ハロゲン原子、水酸基、メルカプト基、シアノ基、ホルミル基、オキソ基、Ｃ１－６アルキル基、Ｃ３－１０シクロアルキル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基、ジ－Ｃ１－６アルキルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジアゼパニル基および式－Ｔ４－Ｔ５　(式中、Ｔ４は、カルボニル基またはスルホニル基を意味する。Ｔ５は、Ｃ１－６アルキル基、Ｃ３－１０シクロアルキル基、アゼチジニル基、ピロリジニル基、ピペリジニル基、水酸基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基またはジ－Ｃ１－６アルキルアミノ基を意味する。)で表される基からなり、上記各基は、水酸基、Ｃ１－６アルキル基、ジ－Ｃ１－６アルキルアミノ基、アゼチジニル基またはピロリジニル基を有していてもよい。
［５］　Ｒ１が、下記置換基群ｅから選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいピロリジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいピペリジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいピペラジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいジアゼパン－１－イル基または下記置換基群ｅから選ばれる置換基を有していてもよいモルホリン－４－イル基である［１］記載の食道癌治療用組成物。
［置換基群ｅ］
メチル基、エチル基、ジメチルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基およびピペラジニル基からなり、上記各基は、水酸基、メチル基、ジメチルアミノ基、アゼチジニル基、ピロリジニル基またはピペリジニル基を有していてもよい。
［６］　Ｒ１が、下記置換基群ｇから選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｇから選ばれる置換基を有するピロリジン－１－イル基、下記置換基群ｇから選ばれる置換基を有するピペリジン－１－イル基または下記置換基群ｇから選ばれる置換基を有するピペラジン－１－イル基である［１］記載の食道癌治療用組成物。
［置換基群ｇ］
ジメチルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジメチルアミノメチル基、ジメチルアミノエチル基、アゼチジン－１－イルメチル基、ピロリジン－１－イルメチル基およびピペリジン－１－イルメチル基からなり、上記各基は、メチル基またはジメチルアミノ基を有していてもよい。
［６－１］　Ｒ１が、下記置換基群ｇ－１から選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｇ－１から選ばれる置換基を有するピロリジン－１－イル基、下記置換基群ｇ－１から選ばれる置換基を有するピペリジン－１－イル基または下記置換基群ｇ－１から選ばれる置換基を有するピペラジン－１－イル基である［１］記載の食道癌治療用組成物。
［置換基群ｇ－１］
アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジメチルアミノメチル基、ジメチルアミノエチル基、アゼチジン－１－イルメチル基、ピロリジン－１－イルメチル基およびピペリジン－１－イルメチル基からなり、上記各基は、メチル基またはジメチルアミノ基を有していてもよい。
［６－２］　Ｒ１が、ジメチルアミノ基を有するアゼチジン－１－イル基、ジメチルアミノ基を有するピロリジン－１－イル基またはジメチルアミノ基を有するピペリジン－１－イル基である［１］記載の食道癌治療用組成物。
［６－３］　Ｒ１が、下記置換基群ｇ－２から選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｇ－２から選ばれる置換基を有するピロリジン－１－イル基または下記置換基群ｇ－２から選ばれる置換基を有するピペリジン－１－イル基である［１］記載の食道癌治療用組成物。
［置換基群ｇ－２］
水酸基、メトキシ基、ヒドロキシメチル基およびジメチルアミノアセトキシ基。
［６－４］　Ｒ１が、［２－（ジメチルアミノ）エチル］ピペラジン－１－イル基、４－ピロリジン－１－イルピペリジン－１－イル基、４－［（ジメチルアミノ）メチル］ピペリジン－１－イル基、４－アゼチジン－１－イルピペリジン－１－イル基、４－［３－（ジメチルアミノ）アゼチジン－１－イル］ピペリジン－１－イル基、４－（４－メチルピペラジン－１－イル）ピペリジン－１－イル基、４－（１－メチルピペリジン－４－イル）ピペラジン－１－イル基、４－（１－メチルアゼチジン－３－イル）ピペラジン－１－イル基、４－（ジメチルアミノ）ピペリジン－１－イル基、４－（アゼチジン－１－イルメチル）ピペリジン－１－イル基、４－（ピロリジン－１－イルメチル）ピペリジン－１－イル基、（３Ｓ）－３－（ジメチルアミノ）ピロリジン－１－イル基、（３Ｒ）－３－（ジメチルアミノ）ピロリジン－１－イル基、アゼチジン－１－イル基、ピロリジン－１－イル基、モルホリン－４－イル基、４－メチルピペラジン－１－イル基、３－ヒドロキシアゼチジン－１－イル基、１，３’－ビアゼチジン－１’－イル基、３－（ヒドロキシメチル）アゼチジン－１－イル基、３－（ジメチルアミノ）アゼチジン－１－イル基、３－［（ジメチルアミノ）メチル］アゼチジン－１－イル基、４－ヒドロキシピペリジン－１－イル基、４－（ヒドロキシメチル）ピペリジン－１－イル基、（３Ｒ）－３－ヒドロキシピロリジン－１－イル基、（３Ｓ）－３－ヒドロキシピロリジン－１－イル基、３－（アゼチジン－１－イルメチル）アゼチジン－１－イル基または３－（２－ジメチルアミノアセトキシ）アゼチジン－１－イル基である［１］記載の食道癌治療用組成物。
［７］　Ｒ１が、式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、上記［１］に記載のＲ１１ａおよびＲ１１ｂと同意義を意味する。）で表される基である［１］記載の食道癌治療用組成物。
［８］　Ｒ１が、式－ＮＲ１１ｃＲ１１ｄ（式中、Ｒ１１ｃは、水素原子またはＣ１－６アルキル基を意味する。Ｒ１１ｄは、Ｃ１－６アルキル基または式
Figure JPOXMLDOC01-appb-C000008
 （式中、ｃは、１ないし３の整数を意味する。Ｚ１は、酸素原子、硫黄原子、カルボニル基、スルホニル基または式－ＮＲＺ１－（式中、ＲＺ１は、水素原子またはＣ１－６アルキル基を意味する。）で表される基を意味する。）で表される基を意味する。ただし、Ｒ１１ｄは上記［１］に記載の置換基群ａまたは置換基群ｂから選ばれる置換基を有していてもよい。）で表される基である［１］記載の食道癌治療用組成物。
［９］　Ｒ１が、式－ＮＲ１１ｅＲ１１ｆ（式中、Ｒ１１ｅは、水素原子またはＣ１－６アルキル基を意味する。Ｒ１１ｆは、Ｃ１－６アルキル基、ピロリジン－３－イル基、ピペリジン－３－イル基、ピペリジン－４－イル基またはテトラヒドロピラン－４－イル基を意味する。ただし、Ｒ１１ｆは、上記［４］に記載の置換基群ｄから選ばれる置換基を有していてもよい。）で表される基である［１］記載の食道癌治療用組成物。
［１０］　Ｒ１が、式－ＮＲ１１ｇＲ１１ｈ（式中、Ｒ１１ｇは、水素原子またはメチル基を意味する。Ｒ１１ｈは、ｎ－プロピル基、ｎ－ブチル基、ピロリジン－３－イル基、ピペリジン－３－イル基、ピペリジン－４－イル基またはテトラヒドロピラン－４－イル基を意味する。ただし、Ｒ１１ｈは、下記置換基群ｆから選ばれる置換基を有していてもよい。）で表される基である［１］記載の食道癌治療用組成物。
［置換基群ｆ］
メチル基、エチル基、ｎ－プロピル基、アセチル基、ジメチルアミノ基、ジエチルアミノ基、アゼチジニル基、ピロリジニル基およびピペラジニル基からなり、上記各基は、メチル基またはジメチルアミノ基を有していてもよい。
［１１］　Ｒ１が、式－Ｎ（ＣＨ３）Ｒ１１ｉ（式中、Ｒ１１ｉは、ｎ－プロピル基、ｎ－ブチル基、ピロリジン－３－イル基またはピペリジン－４－イル基を意味する。ただし、Ｒ１１ｉは、下記置換基群ｈから選ばれる置換基を有する。）で表される基である［１］記載の食道癌治療用組成物。
［置換基群ｈ］
ジメチルアミノ基、ジエチルアミノ基、ジメチルアミノエチル基、ジメチルアミノプロピル基および１－メチルアゼチジン－３－イル基。
［１２］　Ｒ１が、式－Ｎ（ＣＨ３）Ｒ１１ｊ（式中、Ｒ１１ｊは、１－メチルピペリジン－４－イル基または１－エチルピペリジン－４－イル基を意味する。）で表される基である［１］記載の食道癌治療用組成物。
［１２－１］　Ｒ１が、式－Ｎ（ＣＨ３）Ｒ１１ｋ（式中、Ｒ１１ｋは、３－（ジメチルアミノ）プロピル基または１－［２－（ジメチルアミノ）エチル］ピペリジン－４－イル基を意味する。）で表される基である［１］記載の食道癌治療用組成物。
［１２－２］　Ｒ１が、メチル（１－メチルピペリジン－４－イル）アミノ基、（１－エチルピペリジン－４－イル）（メチル）アミノ基、［３－（ジメチルアミノ）プロピル］（メチル）アミノ基または｛１－［２－（ジメチルアミノ）エチル］ピペリジン－４－イル｝（メチル）アミノ基である［１］記載の食道癌治療用組成物。
［１３］　Ｒ４、Ｒ５、Ｒ６およびＲ７が、同一または異なって、水素原子、ハロゲン原子またはＣ１－６アルキル基である［１］～［１２－２］のいずれか１記載の食道癌治療用組成物。
［１４］　Ｒ８が、水素原子である［１］～［１３］のいずれか１記載の食道癌治療用組成物。
［１５］　Ｘが、式－Ｃ（Ｒ１０ａ）＝（式中、Ｒ１０ａは、水素原子、ハロゲン原子またはシアノ基を意味する。）で表される基である［１］～［１４］のいずれか１記載の食道癌治療用組成物。
［１６］　Ｘが、窒素原子である［１］～［１４］のいずれか１記載の食道癌治療用組成物。
［１７］　ｎが、１である［１］～［１６］のいずれか１記載の食道癌治療用組成物。
［１８］　Ｒ９が、上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ１－６アルキルアミノ基、上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ３－１０シクロアルキルアミノ基、上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ６－１０アリールアミノ基、上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－５～１０員へテロアリールアミノ基または上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－４～１０員非芳香族ヘテロ環アミノ基である［１］～［１７］のいずれか１記載の食道癌治療用組成物。
［１９］　Ｒ９が、上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ３－１０シクロアルキルアミノ基または上記［１］に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ６－１０アリールアミノ基である［１］～［１７］のいずれか１記載の食道癌治療用組成物。
［１９－１］　Ｒ９が、下記置換基群ｉから選ばれる置換基を有していてもよいモノ－Ｃ３－１０シクロアルキルアミノ基または下記置換基群ｉから選ばれる置換基を有していてもよいモノ－Ｃ６－１０アリールアミノ基である［１］～［１７］のいずれか１記載の食道癌治療用組成物。
［置換基群ｉ］
ハロゲン原子、トリフルオロメチル基、シアノ基、Ｃ１－６アルキル基およびＣ１－６アルコキシ基。
［１９－２］　Ｒ９が、上記［１９－１］に記載の置換基群ｉから選ばれる置換基を有していてもよいシクロペンチルアミノ基、上記［１９－１］に記載の置換基群ｉから選ばれる置換基を有していてもよいシクロヘキシルアミノ基、上記［１９－１］に記載の置換基群ｉから選ばれる置換基を有していてもよいシクロヘプチルアミノ基または上記［１９－１］に記載の置換基群ｉから選ばれる置換基を有していてもよいフェニルアミノ基である［１］～［１７］のいずれか１記載の食道癌治療用組成物。
［２０］　一般式（Ｉ）で表される化合物が、
（１）Ｎ－［４－（｛２－［（｛４－［２－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｅｔｈｙｌ］ｐｉｐｅｒａｚｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３）Ｎ－（４－Ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（４－ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４）Ｎ－［４－（｛２－［（｛４－［（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ｐｉｐｅｒｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（５）Ｎ－｛４－［（２－｛［（４－Ａｚｅｔｉｄｉｎ－１－ｙｌｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］－２－ｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（６）Ｎ－［４－（｛２－［（｛４－［３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｐｉｐｅｒｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（７）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（８）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ｐｉｐｅｒａｚｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（９）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（１－ｍｅｔｈｙｌａｚｅｔｉｄｉｎ－３－ｙｌ）ｐｉｐｅｒａｚｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１０）Ｎ－（４－｛［２－（｛［４－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１１）Ｎ－（４－｛［２－（｛［４－（Ａｚｅｔｉｄｉｎ－１－ｙｌｍｅｔｈｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１２）Ｎ－（４－Ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［４－（ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｍｅｔｈｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１３）Ｎ－（４－｛［２－（｛［（３Ｓ）－３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１４）Ｎ－（４－｛［２－（｛［（３Ｒ）－３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１５）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１６）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１７）Ｎ－［４－（｛２－［（｛４－［３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｐｉｐｅｒｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１８）Ｎ－（４－｛［２－（｛［（１－Ｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１９）Ｎ－［４－（｛２－［（Ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２０）Ｎ－（４－Ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－［２－ｆｌｕｏｒｏ－４－（｛２－［（ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２１）Ｎ－｛２－Ｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２２）Ｎ－［４－（｛２－［（１，３’－Ｂｉａｚｅｔｉｄｉｎ－１’－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２３）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２４）Ｎ－（４－｛［２－（｛［３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２５）Ｎ－［４－（｛２－［（｛３－［（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ａｚｅｔｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２６）Ｎ－｛２－Ｆｌｕｏｒｏ－４－［（２－｛［（４－ｈｙｄｒｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２７）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２８）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｒ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２９）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｓ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３０）Ｎ－［４－（｛２－［（Ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３１）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３２）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３３）Ｎ－［２，５－Ｄｉｆｌｕｏｒｏ－４－（｛２－［（｛３－［（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ａｚｅｔｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３４）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３５）Ｎ－｛４－［（２－｛［３－（Ａｚｅｔｉｄｉｎ－１－ｙｌｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３６）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３７）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（４－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｍｉｄｉｎ－６－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３８）Ｎ－［４－（｛４－［（｛３－［（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ａｚｅｔｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｍｉｄｉｎ－６－ｙｌ｝ｏｘｙ）－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３９）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［４－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｍｉｄｉｎ－６－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４０）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［４－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｍｉｄｉｎ－６－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４１）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［４－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｍｉｄｉｎ－６－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４２）Ｎ－（４－｛［２－（｛［４－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４３）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４４）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（４－ｈｙｄｒｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４５）Ｎ－｛４－［（２－｛［（４－Ａｚｅｔｉｄｉｎ－１－ｙｌｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｏｘｙ｝－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４６）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［３－（２－ｄｉｍｅｔｈｙｌａｍｉｎｏａｃｅｔｏｘｙ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４７）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｓ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅまたは
（４８）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｒ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅである［１］記載の食道癌治療用組成物。
［２１］　一般式（Ｉ）で表される化合物が、
（１）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（２）Ｎ－［４－（｛２－［（ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（３）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（４）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（５）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（６）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅである［１］記載の食道癌治療用組成物。
［２２］　食道癌の患者に［１］～［２１］のいずれか１記載の食道癌治療用組成物を投与することを特徴とする食道癌の治療方法。
［２３］　食道癌治療用組成物を製造するための、上記一般式（Ｉ）で表される化合物もしくはその塩またはそれらの水和物の使用。
［２４］　食道癌治療用組成物に使用するための、上記一般式（Ｉ）で表される化合物もしくはその塩またはそれらの水和物。 That is, the present invention provides the following [1] to [24].
[1] General formula
Figure JPOXMLDOC01-appb-C000005
 (Where R is1Is a 3- to 10-membered non-aromatic heterocyclic group (provided that the ring-constituting atom always contains a nitrogen atom and has a bond from the nitrogen atom) or the formula —NR11aR11b(Wherein R11aAnd R11bAre the same or different and are a hydrogen atom, C1-6Alkyl group, C3-6Alkenyl group, C3-6Alkynyl group, C3-10A cycloalkyl group, C6-10An aryl group, a 5- to 10-membered heteroaryl group or a 4- to 10-membered non-aromatic heterocyclic group. However, R11aAnd R11bMay have a substituent selected from the following substituent group a or the following substituent group b.
[Substituent group a]
A halogen atom, a hydroxyl group, a mercapto group, a nitro group, a cyano group and an oxo group;
[Substituent group b]
C1-6Alkyl group, C2-6Alkenyl group, C2-6Alkynyl group, C3-10A cycloalkyl group, C6-10Aryl group, 5- to 10-membered heteroaryl group, 3- to 10-membered non-aromatic heterocyclic group, C1-6Alkoxy group, C3-6Alkenyloxy group, C3-6Alkynyloxy group, C3-10Cycloalkoxy group, C6-10Aryloxy group, 5- to 10-membered heteroaryloxy group, 4- to 10-membered non-aromatic heterocyclic oxy group, C1-6Alkylthio group, C3-6Alkenylthio group, C3-6Alkynylthio group, C3-10A cycloalkylthio group, C6-10Arylthio groups, 5- to 10-membered heteroarylthio groups, 4- to 10-membered non-aromatic heterocyclic thio groups and the formula -T1-T2-T3
(Where T1Is a single bond or C1-6An alkylene group is meant.
T2Is a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula —C (═O) —O—, a group represented by the formula —O—C (═O) —, the formula —SO2A group represented by -O-, a formula -O-SO2A group represented by the formula: -NRT1A group represented by the formula: -C (= O) -NRT1A group represented by the formula: -NRT1A group represented by —C (═O) —, the formula —SO2-NRT1A group represented by-or the formula -NRT1-SO2Means a group represented by-.
T3Is a hydrogen atom, C1-6Alkyl group, C3-6Alkenyl group, C3-6Alkynyl group, C3-10A cycloalkyl group, C6-10An aryl group, a 5- to 10-membered heteroaryl group or a 4- to 10-membered non-aromatic heterocyclic group.
RT1Is a hydrogen atom or C1-6An alkyl group is meant. And each of the above groups may have a substituent selected from the following substituent group c.
[Substituent group c]
Halogen atom, hydroxyl group, mercapto group, nitro group, cyano group, oxo group, C1-6Alkyl group, C2-6Alkenyl group, C2-6Alkynyl group, C3-10A cycloalkyl group, C6-10Aryl group, 5- to 10-membered heteroaryl group, 3- to 10-membered non-aromatic heterocyclic group, C1-6Alkoxy group, C1-6Alkylthio group, mono-C1-6Alkylamino groups and di-C1-6An alkylamino group; ).
However, R1May have a substituent selected from the substituent group a or the substituent group b.
R2And R3Means a hydrogen atom.
R4, R5, R6And R7Are the same or different and are a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a trifluoromethyl group, C1-6Alkyl group, C2-6Alkenyl group, C2-6Alkynyl group, C1-6Alkoxy group, amino group, mono-C1-6Alkylamino group, di-C1-6Alkylamino group, formula —CO—R12(Wherein R12Is a hydrogen atom, a hydroxyl group, C1-6Alkyl group, C1-6Alkoxy group, amino group, mono-C1-6Alkylamino group or di-C1-6An alkylamino group is meant. ).
R8Is a hydrogen atom or C1-6An alkyl group is meant.
R9Is a 3- to 10-membered non-aromatic heterocyclic group (provided that the ring-constituting atom always contains a nitrogen atom and has a bond from the nitrogen atom) or the formula —NR11aR11b(Wherein R11aAnd R11bMeans a group represented by a group represented by the same meaning as defined above.
However, R9May have a substituent selected from the substituent group a or the substituent group b.
N means an integer of 1 to 2.
X is the formula -C (R10) = (Where R is10Is a hydrogen atom, a halogen atom, a cyano group, C1-6Alkyl group, C2-6Alkenyl group, C2-6Alkynyl group, formula —CO—R12(Wherein R12Means the same as defined above. ). ) Or a nitrogen atom. )
A composition for treating esophageal cancer comprising a compound represented by the formula:
[2] R1Is a 3- to 10-membered non-aromatic heterocyclic group (however, in the atoms constituting the ring, which may have a substituent selected from the substituent group a or the substituent group b described in [1] above) The composition for treating esophageal cancer according to [1], wherein a nitrogen atom is necessarily contained in and a bond is derived from the nitrogen atom).
[3] R1May have a substituent selected from the substituent group a or the substituent group b described in [1] above
Figure JPOXMLDOC01-appb-C000006
 (Wherein a represents an integer of 1 to 4) or a substituent selected from substituent group a or substituent group b described in [1] above. Good expression
Figure JPOXMLDOC01-appb-C000007
 (Wherein b represents an integer of 1 to 3. Z represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, or a formula —NR.Z-(Wherein RZIs a hydrogen atom or C1-6An alkyl group is meant. ). The composition for treating esophageal cancer according to [1], which is a group represented by:
[4] R1Is an azetidin-1-yl group which may have a substituent selected from the following substituent group d, a pyrrolidin-1-yl group which may have a substituent selected from the following substituent group d, A piperidin-1-yl group optionally having a substituent selected from the following substituent group d; an azepan-1-yl group optionally having a substituent selected from the following substituent group d; A piperazin-1-yl group optionally having a substituent selected from group d, a diazepan-1-yl group optionally having a substituent selected from substituent group d below, and the following substituent group a morpholin-4-yl group optionally having a substituent selected from d, a thiomorpholin-4-yl group optionally having a substituent selected from the following substituent group d, or the following substituent group d 1,1-dioxy optionally having a substituent selected from Thiomorpholine-4-yl group [1] for treating esophageal cancer composition.
[Substituent group d]
Halogen atom, hydroxyl group, mercapto group, cyano group, formyl group, oxo group, C1-6Alkyl group, C3-10A cycloalkyl group, C1-6Alkoxy group, amino group, mono-C1-6Alkylamino group, di-C1-6Alkylamino, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, diazepanyl and formula -T4-T5(Where T4Means a carbonyl group or a sulfonyl group. T5Is C1-6Alkyl group, C3-10Cycloalkyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, hydroxyl group, C1-6Alkoxy group, amino group, mono-C1-6Alkylamino group or di-C1-6An alkylamino group is meant. ), And each of the above groups is a hydroxyl group, C1-6Alkyl group, di-C1-6It may have an alkylamino group, an azetidinyl group or a pyrrolidinyl group.
[5] R1Azetidin-1-yl group optionally having a substituent selected from the following substituent group e, pyrrolidin-1-yl group optionally having a substituent selected from the following substituent group e, A piperidin-1-yl group optionally having a substituent selected from the following substituent group e; a piperazin-1-yl group optionally having a substituent selected from the following substituent group e; A diazepan-1-yl group optionally having a substituent selected from group e or a morpholin-4-yl group optionally having a substituent selected from substituent group e below [1] The composition for esophageal cancer treatment as described.
[Substituent group e]
It consists of a methyl group, an ethyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group and a piperazinyl group, each of the above groups having a hydroxyl group, a methyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group or a piperidinyl group. May be.
[6] R1Is an azetidin-1-yl group optionally having a substituent selected from the following substituent group g, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g, and the following substituent group g The composition for treating esophageal cancer according to [1], which is a piperidin-1-yl group having a substituent selected from: or a piperazin-1-yl group having a substituent selected from the following substituent group g:
[Substituent group g]
Consisting of dimethylamino group, azetidinyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group, dimethylaminomethyl group, dimethylaminoethyl group, azetidin-1-ylmethyl group, pyrrolidin-1-ylmethyl group and piperidin-1-ylmethyl group, Each group may have a methyl group or a dimethylamino group.
[6-1] R1Azetidin-1-yl group optionally having a substituent selected from the following substituent group g-1, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g-1, The treatment for esophageal cancer according to [1], which is a piperidin-1-yl group having a substituent selected from the substituent group g-1 or a piperazin-1-yl group having a substituent selected from the following substituent group g-1 Composition.
[Substituent group g-1]
An azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a dimethylaminomethyl group, a dimethylaminoethyl group, an azetidin-1-ylmethyl group, a pyrrolidin-1-ylmethyl group, and a piperidin-1-ylmethyl group, It may have a methyl group or a dimethylamino group.
[6-2] R1The composition for treating esophageal cancer according to [1], wherein is an azetidin-1-yl group having a dimethylamino group, a pyrrolidin-1-yl group having a dimethylamino group, or a piperidin-1-yl group having a dimethylamino group .
[6-3] R1Is an azetidin-1-yl group optionally having a substituent selected from the following substituent group g-2, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g-2, or The composition for treating esophageal cancer according to [1], which is a piperidin-1-yl group having a substituent selected from substituent group g-2.
[Substituent group g-2]
Hydroxyl group, methoxy group, hydroxymethyl group and dimethylaminoacetoxy group.
[6-4] R1[2- (dimethylamino) ethyl] piperazin-1-yl group, 4-pyrrolidin-1-ylpiperidin-1-yl group, 4-[(dimethylamino) methyl] piperidin-1-yl group, 4- Azetidin-1-ylpiperidin-1-yl group, 4- [3- (dimethylamino) azetidin-1-yl] piperidin-1-yl group, 4- (4-methylpiperazin-1-yl) piperidin-1- Yl group, 4- (1-methylpiperidin-4-yl) piperazin-1-yl group, 4- (1-methylazetidin-3-yl) piperazin-1-yl group, 4- (dimethylamino) piperidine- 1-yl group, 4- (azetidin-1-ylmethyl) piperidin-1-yl group, 4- (pyrrolidin-1-ylmethyl) piperidin-1-yl group, (3S) -3- (dimethylamino) Loridin-1-yl group, (3R) -3- (dimethylamino) pyrrolidin-1-yl group, azetidin-1-yl group, pyrrolidin-1-yl group, morpholin-4-yl group, 4-methylpiperazine- 1-yl group, 3-hydroxyazetidin-1-yl group, 1,3′-biazetidin-1′-yl group, 3- (hydroxymethyl) azetidin-1-yl group, 3- (dimethylamino) azetidine- 1-yl group, 3-[(dimethylamino) methyl] azetidin-1-yl group, 4-hydroxypiperidin-1-yl group, 4- (hydroxymethyl) piperidin-1-yl group, (3R) -3- Hydroxypyrrolidin-1-yl group, (3S) -3-hydroxypyrrolidin-1-yl group, 3- (azetidin-1-ylmethyl) azetidin-1-yl group or 3- (2- Methylamino acetoxy) azetidin-1-yl is based on [1] for treating esophageal cancer composition.
[7] R1Is the formula -NR11aR11b(Wherein R11aAnd R11bIs R according to [1] above.11aAnd R11bMeans the same. The composition for treating esophageal cancer according to [1], which is a group represented by:
[8] R1Is the formula -NR11cR11d(Wherein R11cIs a hydrogen atom or C1-6An alkyl group is meant. R11dIs C1-6Alkyl group or formula
Figure JPOXMLDOC01-appb-C000008
 (Wherein c represents an integer of 1 to 3. Z1Is an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group or a formula —NRZ1-(Wherein RZ1Is a hydrogen atom or C1-6An alkyl group is meant. ). ). However, R11dMay have a substituent selected from the substituent group a or the substituent group b described in [1] above. The composition for treating esophageal cancer according to [1], which is a group represented by:
[9] R1Is the formula -NR11eR11f(Wherein R11eIs a hydrogen atom or C1-6An alkyl group is meant. R11fIs C1-6It means an alkyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group. However, R11fMay have a substituent selected from the substituent group d described in [4] above. The composition for treating esophageal cancer according to [1], which is a group represented by:
[10] R1Is the formula -NR11gR11h(Wherein R11gMeans a hydrogen atom or a methyl group. R11hMeans an n-propyl group, n-butyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group. However, R11hMay have a substituent selected from the following substituent group f. The composition for treating esophageal cancer according to [1], which is a group represented by:
[Substituent group f]
It consists of a methyl group, an ethyl group, an n-propyl group, an acetyl group, a dimethylamino group, a diethylamino group, an azetidinyl group, a pyrrolidinyl group, and a piperazinyl group, and each of the above groups may have a methyl group or a dimethylamino group .
[11] R1Is of the formula —N (CH3) R11i(Wherein R11iMeans n-propyl, n-butyl, pyrrolidin-3-yl or piperidin-4-yl. However, R11iHas a substituent selected from the following substituent group h. The composition for treating esophageal cancer according to [1], which is a group represented by:
[Substituent group h]
Dimethylamino group, diethylamino group, dimethylaminoethyl group, dimethylaminopropyl group and 1-methylazetidin-3-yl group.
[12] R1Is of the formula —N (CH3) R11j(Wherein R11jMeans 1-methylpiperidin-4-yl group or 1-ethylpiperidin-4-yl group. The composition for treating esophageal cancer according to [1], which is a group represented by:
[12-1] R1Is of the formula —N (CH3) R11k(Wherein R11kMeans a 3- (dimethylamino) propyl group or a 1- [2- (dimethylamino) ethyl] piperidin-4-yl group. The composition for treating esophageal cancer according to [1], which is a group represented by:
[12-2] R1Is a methyl (1-methylpiperidin-4-yl) amino group, (1-ethylpiperidin-4-yl) (methyl) amino group, [3- (dimethylamino) propyl] (methyl) amino group or {1- The composition for treating esophageal cancer according to [1], which is a [2- (dimethylamino) ethyl] piperidin-4-yl} (methyl) amino group.
[13] R4, R5, R6And R7Are the same or different and each represents a hydrogen atom, a halogen atom or C1-6The composition for treating esophageal cancer according to any one of [1] to [12-2], which is an alkyl group.
[14] R8The composition for treating esophageal cancer according to any one of [1] to [13], wherein is a hydrogen atom.
[15] X is the formula -C (R10a) = (Where R is10aMeans a hydrogen atom, a halogen atom or a cyano group. The composition for treating esophageal cancer according to any one of [1] to [14], which is a group represented by:
[16] The composition for treating esophageal cancer according to any one of [1] to [14], wherein X is a nitrogen atom.
[17] The composition for treating esophageal cancer according to any one of [1] to [16], wherein n is 1.
[18] R9May have a substituent selected from the substituent group a or the substituent group b described in [1] above.1-6Mono-C which may have an alkylamino group and a substituent selected from substituent group a or substituent group b described in [1] above3-10A cycloalkylamino group, which may have a substituent selected from the substituent group a or the substituent group b described in [1] above;6-10An arylamino group, a mono-5 to 10-membered heteroarylamino group optionally having a substituent selected from the substituent group a or the substituent group b described in [1] above, or the above [1] Any one of [1] to [17], which is a mono-4- to 10-membered non-aromatic heterocyclic amino group optionally having a substituent selected from the substituent group a or the substituent group b A composition for treating esophageal cancer.
[19] R9May have a substituent selected from the substituent group a or the substituent group b described in [1] above.3-10Mono-C which may have a cycloalkylamino group or a substituent selected from the substituent group a or the substituent group b described in [1] above6-10The composition for treating esophageal cancer according to any one of [1] to [17], which is an arylamino group.
[19-1] R9May have a substituent selected from the following substituent group i:3-10Mono-C which may have a cycloalkylamino group or a substituent selected from the following substituent group i6-10The composition for treating esophageal cancer according to any one of [1] to [17], which is an arylamino group.
[Substituent group i]
Halogen atom, trifluoromethyl group, cyano group, C1-6Alkyl groups and C1-6An alkoxy group;
[19-2] R9Is a cyclopentylamino group optionally having a substituent selected from the substituent group i described in [19-1], and a substituent selected from the substituent group i described in [19-1]. A cyclohexylamino group which may have, a cycloheptylamino group which may have a substituent selected from the substituent group i described in [19-1] above, or the substitution described in [19-1] above The composition for treating esophageal cancer according to any one of [1] to [17], which is a phenylamino group which may have a substituent selected from group i.
[20] The compound represented by the general formula (I) is
(1) N- [4-({2-[({4- [2- (Dimethylamino) ethyl] piperazin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide,
(2) N- (2-Fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(3) N- (4-Fluorophenyl) -N ′-{2-fluoro-4-[(2-{[(4-pyrrolidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} cyclopropane-1,1-dicboxamide,
(4) N- [4-({2-[({4-[(Dimethylamino) methyl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorphenyl] -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(5) N- {4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] -2-fluorophenyl} -N ′-(4 -Fluorphenyl) cyclopropane-1,1-dicboxamide,
(6) N- [4-({2-[({4- [3- (Dimethylamino) azetinin-1-yl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2- fluorphenyl] -N ′-(4-fluorphenyl) cyclopropane-1,1-dicboxamide,
(7) N- (2-Fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(8) N- (2-Fluoro-4-{[2-({[4- (1-methylpiperidin-4-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(9) N- (2-Fluoro-4-{[2-({[4- (1-methylazetidin-3-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(10) N- (4-{[2-({[4- (Dimethylamino) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(11) N- (4-{[2-({[4- (Azetidin-1-ylmethyl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(12) N- (4-Fluorophenyl) -N ′-(2-fluoro-4-{[2-({[4- (pyrrolidin-1-ylmethyl) piperidin-1-yl] carbonyl} amino) pyridin-4 -Yl] oxy} phenyl) cyclopropane-1,1-dicboxamide,
(13) N- (4-{[2-({[(3S) -3- (Dimethylamino) pyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(14) N- (4-{[2-({[(3R) -3- (Dimethylamino) pyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(15) N- (2-Fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-phenylcyclopropane -1,1-dicarboxamide,
(16) N- (2-Fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-phenylcyclopropane-1, 1-dicboxamide,
(17) N- [4-({2-[({4- [3- (Dimethylamino) azetinin-1-yl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2- fluorphenyl] -N′-phenylcyclopropane-1,1-dicboxamide,
(18) N- (4-{[2-({[(1-Ethylpiperidin-4-yl) (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N'- phenylcyclopropane-1, 1-dicboxamide,
(19) N- [4-({2-[(Azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1- dicarboxamide,
(20) N- (4-Fluorophenyl) -N ′-[2-fluoro-4-({2-[(pyrrolidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) phenyl] cyclopropane-1,1 -Dicarboxamide,
(21) N- {2-Fluoro-4-[(2-{[(3-hydroxyazetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N '-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(22) N- [4-({2-[(1,3′-Biacetidin-1′-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(23) N- (2-Fluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4 -Fluorphenyl) cyclopropane-1,1-dicboxamide,
(24) N- (4-{[2-({[3- (Dimethylamino) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(25) N- [4-({2-[({3-[(Dimethylamino) methyl] azetinin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorphenyl] -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(26) N- {2-Fluoro-4-[(2-{[(4-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(27) N- (2-Fluoro-4-{[2-({[4- (hydroxymethyl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4 -Fluorphenyl) cyclopropane-1,1-dicboxamide,
(28) N- (2-Fluoro-4-{[2-({[(3R) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(29) N- (2-Fluoro-4-{[2-({[(3S) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(30) N- [4-({2-[(Azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2,5-difluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(31) N- {2,5-Difluoro-4--4-[(2-{[(3-hydroxyzetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(32) N- (2,5-Difluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(33) N- [2,5-Difluoro-4--4-({2-[({3-[(dimethylamino) methyl] azetinin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) phenyl]- N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(34) N- (2,5-Difluoro-4--4-[[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(35) N- {4-[(2-{[3- (Azetidin-1-ylmethyl) azetinin-1-ylcarbonyl] amino} pyridin-4-yl) oxy] -2,5-difluorophenyl} -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(36) N- (2,5-Difluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(37) N- {2,5-Difluoro-4--4-[(4-{[(3-hydroxyzetidin-1-yl) carbonyl] amino} pyrimidin-6-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(38) N- [4-({4-[({3-[(Dimethylamino) methyl] azetinin-1-yl} carbonyl) amino] pyrimidin-6-yl} oxy) -2,5-difluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide,
(39) N- (2,5-Difluoro-4-{[4-({[3- (hydroxymethyl) azetinin-1-yl] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N'- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(40) N- (2,5-Difluoro-4-{[4-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N ' -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(41) N- (2,5-Difluoro-4--4-{[4-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(42) N- (4-{[2-({[4- (Dimethylamino) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2,5-difluorophenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(43) N- {2,5-Difluoro-4--4-[(2-{[(4-methylpiperazin-1-yl) carbonyl] amino} pyridin-4-yl] oxy} phenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(44) N- {2,5-Difluoro-4--4-[(2-{[(4-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(45) N- {4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] oxy} -2,5-difluorophenyl} -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide,
(46) N- (2,5-Difluoro-4--4-[[2-({[3- (2-dimethylaminoacetoxy) azetinin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(47) N- (2,5-Difluoro-4--4-[[2-({[(3S) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide or
(48) N- (2,5-Difluoro-4-{[2-({[(3R) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ The composition for treating esophageal cancer according to [1], which is-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide.
[21] The compound represented by the general formula (I) is
(1) N- (2-Fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide
(2) N- [4-({2-[(azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1- dicarboxamide
(3) N- {2,5-Difluoro-4--4-[(2-{[(3-hydroxyzetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1,1-dicboxamide
(4) N- (2,5-Difluoro-4--4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide
(5) N- (2,5-Difluoro-4--4-[[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide
(6) N- (2,5-Difluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'- The composition for treating esophageal cancer according to [1], which is (4-fluorophenyl) cyclopropane-1, 1-dicboxamide.
[22] A method for treating esophageal cancer, comprising administering the composition for treating esophageal cancer according to any one of [1] to [21] to a patient with esophageal cancer.
[23] Use of the compound represented by the above general formula (I) or a salt thereof or a hydrate thereof for producing a composition for treating esophageal cancer.
[24] A compound represented by the above general formula (I) or a salt thereof or a hydrate thereof for use in a composition for treating esophageal cancer.
　国際公開第２００７／０２３７６８号パンフレットに開示されているように、本発明に係る化合物は、ＨＧＦＲチロシンキナーゼ阻害作用を有し、ＨＧＦＲ活性化に基づくヒト癌細胞の増殖を阻害する。また、本発明に係る化合物は、ヒト癌細胞の遊走を阻害する。さらに本発明に係る化合物は、ＨＧＦ－ＨＧＦＲシグナルを介した血管内皮細胞の増殖を阻害する。 As disclosed in WO 2007/023768, the compound according to the present invention has an HGFR tyrosine kinase inhibitory action and inhibits the growth of human cancer cells based on HGFR activation. In addition, the compound according to the present invention inhibits migration of human cancer cells. Furthermore, the compounds according to the invention inhibit the proliferation of vascular endothelial cells via the HGF-HGFR signal.
　本発明に係る化合物は、ヒト食道癌細胞の増殖を阻害する（薬理試験例１）。したがって、本発明に係る化合物は食道癌治療用組成物として有用である。 The compound according to the present invention inhibits the growth of human esophageal cancer cells (Pharmacological Test Example 1). Therefore, the compound according to the present invention is useful as a composition for treating esophageal cancer.
　しかしながら、癌治療用組成物または癌治療剤の対象となる癌種は、特に限定されず、例えば、脳腫瘍（下垂体腺腫、神経膠腫を含む）、頭頸部癌、頚癌、顎癌、上顎癌、顎下腺癌、口腔癌（舌癌、口腔底癌、歯肉癌、頬粘膜癌、硬口蓋癌を含む）、唾液腺癌、舌下腺癌、耳下腺癌、鼻腔癌、副鼻腔癌（上顎洞癌、前頭洞癌、篩骨洞癌、蝶形骨洞癌を含む）、喉頭癌（声門上癌、声門癌、声門下癌を含む）、食道癌、肺癌（気管支原生癌、非小細胞肺癌（肺腺癌、扁平上皮癌、大細胞肺癌を含む）、小細胞肺癌（燕麦細胞型（リンパ球様型）、中間細胞型を含む）、混在小細胞・大細胞肺癌を含む）、乳癌、膵癌（膵管癌を含む）、胃癌（スキルス胃癌、未分化胃癌を含む）、胆道癌（胆管癌、胆嚢癌を含む）、小腸または十二指腸の癌、大腸癌（結腸癌、直腸癌、盲腸癌、Ｓ状結腸癌、上行結腸癌、横行結腸癌、下行結腸癌を含む）、膀胱癌、腎癌（腎細胞癌を含む）、肝癌（肝細胞癌、肝内胆管癌を含む）、前立腺癌、子宮癌（子宮頸癌、子宮体癌を含む）、卵巣癌、甲状腺癌、咽頭癌（上咽頭癌、中咽頭癌、下咽頭癌を含む）、肉腫（例えば、骨肉腫、軟骨肉腫、カポジ肉腫、筋肉腫、血管肉腫、繊維肉腫など）、悪性リンパ腫（ホジキン型リンパ腫、非ホジキン型リンパ腫を含む）、白血病（例えば、慢性骨髄性白血病（ＣＭＬ）、急性骨髄白血病（ＡＭＬ）、慢性リンパ球性白血病（ＣＬＬ）および急性リンパ性白血病（ＡＬＬ）、リンパ腫、多発性骨髄腫（ＭＭ）、骨髄異型成症候群等を含む）、皮膚癌（基底細胞癌、有棘細胞癌、悪性黒色腫、菌状息肉症、セザリー症候群、日光角化症、ボーエン病、バージェット病を含む）およびメラノーマなどを挙げることができる。 However, the cancer type that is the target of the cancer therapeutic composition or cancer therapeutic agent is not particularly limited, and examples thereof include brain tumors (including pituitary adenoma and glioma), head and neck cancer, cervical cancer, jaw cancer, and maxilla. Cancer, submandibular gland cancer, oral cancer (including tongue cancer, oral floor cancer, gingival cancer, buccal mucosa cancer, hard palate cancer), salivary gland cancer, sublingual gland cancer, parotid gland cancer, nasal cavity cancer, sinus cancer (Including maxillary sinus cancer, frontal sinus cancer, ethmoid sinus cancer, sphenoid sinus cancer), laryngeal cancer (including supraglottic cancer, glottic cancer, subglottic cancer), esophageal cancer, lung cancer (primary bronchial cancer, non-bronchial cancer) Small cell lung cancer (including lung adenocarcinoma, squamous cell carcinoma, large cell lung cancer), small cell lung cancer (including buckwheat cell type (lymphocyte-like type), intermediate cell type), mixed small cell / large cell lung cancer) Breast cancer, pancreatic cancer (including pancreatic duct cancer), gastric cancer (including Skills gastric cancer, undifferentiated gastric cancer), biliary tract cancer (including bile duct cancer, gallbladder cancer), small intestine or duodenal cancer, Intestinal cancer (including colon cancer, rectal cancer, cecal cancer, sigmoid colon cancer, ascending colon cancer, transverse colon cancer, descending colon cancer), bladder cancer, renal cancer (including renal cell carcinoma), liver cancer (hepatocellular carcinoma) , Including intrahepatic bile duct cancer), prostate cancer, uterine cancer (including cervical cancer, endometrial cancer), ovarian cancer, thyroid cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, hypopharyngeal cancer), Sarcomas (eg, osteosarcoma, chondrosarcoma, Kaposi's sarcoma, myoma, angiosarcoma, fibrosarcoma, etc.), malignant lymphoma (including Hodgkin-type lymphoma, non-Hodgkin-type lymphoma), leukemia (eg, chronic myelogenous leukemia (CML)) Acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and acute lymphocytic leukemia (ALL), lymphoma, multiple myeloma (MM), myelodysplastic syndrome, etc.), skin cancer (basal cell carcinoma) , Squamous cell carcinoma, malignant melanoma, mycosis fungoides, sezari Syndrome, actinic keratosis, Bowen's disease, including bar jet's disease) and melanoma, and the like.
　以下に、本明細書において記載する記号、用語等の定義等を示して、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail with definitions of symbols, terms and the like described in the present specification.
　本明細書中においては、化合物の構造式が便宜上一定の異性体を表すことがあるが、本発明には化合物の構造上生ずる全ての幾何異性体、不斉炭素に基づく光学異性体、立体異性体、互変異性体等の異性体および異性体混合物を含み、便宜上の式の記載に限定されるものではなく、いずれか一方の異性体でも混合物でもよい。したがって、本発明の化合物には、分子内に不斉炭素原子を有し光学活性体およびラセミ体が存在することがありうるが、本発明においては一方に限定されず、いずれもが含まれる。また、結晶多形が存在することもあるが同様に限定されず、いずれかの結晶形が単一であっても結晶形混合物であってもよい。そして、本発明に係る化合物には無水物と水和物が包含される。 In the present specification, the structural formula of a compound may represent a certain isomer for convenience, but the present invention includes all geometric isomers, optical isomers based on asymmetric carbon, and stereoisomerism that occur in the structure of the compound. Isomers such as isomers and tautomers, and mixtures of isomers, and are not limited to the description of the formula for convenience, and may be either isomer or mixture. Therefore, the compound of the present invention may have an asymmetric carbon atom in the molecule, and an optically active substance and a racemate may exist. However, the present invention is not limited to one and includes both. In addition, there are cases where crystal polymorphism may exist, but it is not limited in the same manner, and any one of the crystal forms may be a single crystal form or a mixture of crystal forms. The compounds according to the present invention include anhydrides and hydrates.
　また、本発明に係る化合物が生体内で酸化、還元、加水分解、抱合等の代謝を受けて生じる化合物（いわゆる代謝物）、生体内で酸化、還元、加水分解、抱合等の代謝を受けて本発明に係る化合物を生成する化合物（いわゆるプロドラッグ）も本発明の特許請求の範囲に包含される。 In addition, a compound (so-called metabolite) produced by metabolism, such as oxidation, reduction, hydrolysis, and conjugation, in vivo, and a compound according to the present invention undergoes metabolism such as oxidation, reduction, hydrolysis, and conjugation in vivo. The compounds that produce the compounds according to the present invention (so-called prodrugs) are also encompassed by the claims of the present invention.
　「塩」とは、例えば無機酸との塩、有機酸との塩、無機塩基との塩、有機塩基との塩、酸性または塩基性アミノ酸との塩などがあげられ、中でも薬理学的に許容される塩が好ましい。 The “salt” includes, for example, a salt with an inorganic acid, a salt with an organic acid, a salt with an inorganic base, a salt with an organic base, a salt with an acidic or basic amino acid, etc., among which pharmacologically acceptable. The salts to be prepared are preferred.
　無機酸との塩の好適な例としては、例えば塩酸、臭化水素酸、硫酸、硝酸、リン酸などとの塩があげられる。有機酸との塩の好適な例としては、例えば酢酸、コハク酸、フマル酸、マレイン酸、酒石酸、クエン酸、乳酸、ステアリン酸、安息香酸、メタンスルホン酸、エタンスルホン酸、ｐ－トルエンスルホン酸などとの塩があげられる。 Preferable examples of the salt with inorganic acid include salts with hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like. Preferable examples of salts with organic acids include acetic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, lactic acid, stearic acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid. And salt.
　無機塩基との塩の好適な例としては、例えばナトリウム塩、カリウム塩などのアルカリ金属塩、カルシウム塩、マグネシウム塩などのアルカリ土類金属塩、アルミニウム塩、アンモニウム塩などがあげられる。有機塩基との塩の好適な例としては、例えばジエチルアミン、ジエタノールアミン、メグルミン、Ｎ，Ｎ－ジベンジルエチレンジアミンなどとの塩があげられる。 Preferable examples of salts with inorganic bases include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, aluminum salt and ammonium salt. Preferable examples of the salt with an organic base include salts with diethylamine, diethanolamine, meglumine, N, N-dibenzylethylenediamine and the like.
　酸性アミノ酸との塩の好適な例としては、例えばアスパラギン酸、グルタミン酸などとの塩があげられる。塩基性アミノ酸との塩の好適な例としては、例えばアルギニン、リジン、オルニチンなどとの塩があげられる。 Preferable examples of the salt with acidic amino acid include salts with aspartic acid, glutamic acid and the like. Preferable examples of the salt with basic amino acid include salts with arginine, lysine, ornithine and the like.
　「ハロゲン原子」とは、フッ素原子、塩素原子、臭素原子またはヨウ素原子を意味する。 “Halogen atom” means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
　「Ｃ１－６アルキル基」とは、炭素数１ないし６個の直鎖状または分枝鎖状のアルキル基を意味し、具体例としては、メチル基、エチル基、１－プロピル基（ｎ－プロピル基）、２－プロピル基（ｉ－プロピル基）、２－メチル－１－プロピル基（ｉ－ブチル基）、２－メチル－２－プロピル基（ｔ－ブチル基）、１－ブチル基（ｎ－ブチル基）、２－ブチル基（ｓ－ブチル基）、１－ペンチル基、２－ペンチル基、３－ペンチル基、２－メチル－１－ブチル基、３－メチル－１－ブチル基、２－メチル－２－ブチル基、３－メチル－２－ブチル基、２，２－ジメチル－１－プロピル基、１－へキシル基、２－へキシル基、３－へキシル基、２－メチル－１－ペンチル基、３－メチル－１－ペンチル基、４－メチル－１－ペンチル基、２－メチル－２－ペンチル基、３－メチル－２－ペンチル基、４－メチル－２－ペンチル基、２－メチル－３－ペンチル基、３－メチル－３－ペンチル基、２，３－ジメチル－１－ブチル基、３，３－ジメチル－１－ブチル基、２，２－ジメチル－１－ブチル基、２－エチル－１－ブチル基、３，３－ジメチル－２－ブチル基、２，３－ジメチル－２－ブチル基などがあげられる。 The “C 1-6 alkyl group” means a linear or branched alkyl group having 1 to 6 carbon atoms. Specific examples thereof include a methyl group, an ethyl group, a 1-propyl group (n -Propyl group), 2-propyl group (i-propyl group), 2-methyl-1-propyl group (i-butyl group), 2-methyl-2-propyl group (t-butyl group), 1-butyl group (N-butyl group), 2-butyl group (s-butyl group), 1-pentyl group, 2-pentyl group, 3-pentyl group, 2-methyl-1-butyl group, 3-methyl-1-butyl group 2-methyl-2-butyl group, 3-methyl-2-butyl group, 2,2-dimethyl-1-propyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 2- Methyl-1-pentyl group, 3-methyl-1-pentyl group, 4-methyl-1-pentyl group, 2-methyl Tyl-2-pentyl group, 3-methyl-2-pentyl group, 4-methyl-2-pentyl group, 2-methyl-3-pentyl group, 3-methyl-3-pentyl group, 2,3-dimethyl-1 -Butyl group, 3,3-dimethyl-1-butyl group, 2,2-dimethyl-1-butyl group, 2-ethyl-1-butyl group, 3,3-dimethyl-2-butyl group, 2,3- Examples thereof include a dimethyl-2-butyl group.
　「Ｃ２－６アルケニル基」とは、二重結合を１個有する、炭素数２ないし６個の直鎖状または分枝鎖状のアルケニル基を意味し、具体例としては、エテニル基（ビニル基）、１－プロペニル基、２－プロペニル基（アリル基）、１－ブテニル基、２－ブテニル基、３－ブテニル基、ペンテニル基、ヘキセニル基などがあげられる。 The “C 2-6 alkenyl group” means a straight or branched alkenyl group having 2 to 6 carbon atoms having one double bond. As a specific example, an ethenyl group (vinyl Group), 1-propenyl group, 2-propenyl group (allyl group), 1-butenyl group, 2-butenyl group, 3-butenyl group, pentenyl group, hexenyl group and the like.
　「Ｃ３－６アルケニル基」とは、二重結合を１個有する、炭素数３ないし６個の直鎖状または分枝鎖状のアルケニル基を意味し、具体例としては、２－プロペニル基（アリル基）、２－ブテニル基、３－ブテニル基、ペンテニル基、ヘキセニル基などがあげられる。 The “C 3-6 alkenyl group” means a straight or branched alkenyl group having 3 to 6 carbon atoms having one double bond, and specific examples include a 2-propenyl group. (Allyl group), 2-butenyl group, 3-butenyl group, pentenyl group, hexenyl group and the like.
　「Ｃ２－６アルキニル基」とは、三重結合を１個有する、炭素数２ないし６個の直鎖状または分枝鎖状のアルキニル基を意味し、具体例としては、エチニル基、１－プロピニル基、２－プロピニル基、１－ブチニル基、２－ブチニル基、３－ブチニル基、ペンチニル基、ヘキシニル基などがあげられる。 The “C 2-6 alkynyl group” means a straight or branched alkynyl group having 1 to 3 carbon atoms and having one triple bond. Specific examples thereof include an ethynyl group, 1- Examples include propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, pentynyl group, hexynyl group and the like.
　「Ｃ３－６アルキニル基」とは、三重結合を１個有する、炭素数３ないし６個の直鎖状または分枝鎖状のアルキニル基を意味し、具体例としては、２－プロピニル基、２－ブチニル基、３－ブチニル基、ペンチニル基、ヘキシニル基などがあげられる。 The “C 3-6 alkynyl group” means a straight or branched alkynyl group having 3 to 6 carbon atoms having one triple bond. Specific examples thereof include a 2-propynyl group, Examples thereof include 2-butynyl group, 3-butynyl group, pentynyl group, hexynyl group and the like.
　「Ｃ１－６アルキレン基」とは、上記定義「Ｃ１－６アルキル基」からさらに任意の水素原子を１個除いて誘導される二価の基を意味し、具体例としては、メチレン基、１，２－エチレン基、１，１－エチレン基、１，３－プロピレン基、テトラメチレン基、ペンタメチレン基、ヘキサメチレン基などがあげられる。 The “C 1-6 alkylene group” means a divalent group derived by removing one arbitrary hydrogen atom from the above-defined “C 1-6 alkyl group”, and specific examples thereof include a methylene group. 1,2-ethylene group, 1,1-ethylene group, 1,3-propylene group, tetramethylene group, pentamethylene group, hexamethylene group and the like.
　「Ｃ３－１０シクロアルキル基」とは、炭素数が３ないし１０個の単環または二環の飽和脂肪族炭化水素基を意味し、具体例としては、シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基、シクロヘプチル基、シクロオクチル基、シクロノニル基、シクロデシル基、ビシクロ[２．１．０]ペンチル基、ビシクロ[３．１．０]ヘキシル基、ビシクロ[２．１．１]ヘキシル基、ビシクロ[４．１．０]ヘプチル基、ビシクロ[２．２．１]ヘプチル基（ノルボルニル基）、ビシクロ[３．３．０]オクチル基、ビシクロ[３．２．１]オクチル基、ビシクロ[２．２．２]オクチル基、ビシクロ[４．３．０]ノニル基、ビシクロ[３．３．１]ノニル基、ビシクロ[４．４．０]デシル基（デカリル基）、ビシクロ[３．３．２]デシル基などがあげられる。 The “C 3-10 cycloalkyl group” means a monocyclic or bicyclic saturated aliphatic hydrocarbon group having 3 to 10 carbon atoms. Specific examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group. Cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclononyl group, cyclodecyl group, bicyclo [2.1.0] pentyl group, bicyclo [3.1.0] hexyl group, bicyclo [2.1.1] hexyl group , Bicyclo [4.1.0] heptyl group, bicyclo [2.2.1] heptyl group (norbornyl group), bicyclo [3.3.0] octyl group, bicyclo [3.2.1] octyl group, bicyclo [2.2.2] octyl group, bicyclo [4.3.0] nonyl group, bicyclo [3.3.1] nonyl group, bicyclo [4.4.0] decyl group (decalyl group), bicyclo [3 3.2] Decyl group I can get lost.
　「Ｃ６－１０アリール基」とは、炭素数が６ないし１０個の芳香族の炭化水素環式基を意味し、具体例としては、フェニル基、１－ナフチル基、２－ナフチル基、インデニル基、アズレニル基、ヘプタレニル基などがあげられる。 The “C 6-10 aryl group” means an aromatic hydrocarbon cyclic group having 6 to 10 carbon atoms, and specific examples thereof include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, an indenyl group. Group, azulenyl group, heptalenyl group and the like.
　「ヘテロ原子」とは、窒素原子、酸素原子または硫黄原子を意味する。 “Hetero atom” means nitrogen atom, oxygen atom or sulfur atom.
　「５～１０員ヘテロアリール基」とは、環を構成する原子の数が５ないし１０個であり、環を構成する原子中に１ないし５個のヘテロ原子を含有する芳香族性の環式基を意味し、具体例としては、フリル基、チエニル基、ピロリル基、イミダゾリル基、トリアゾリル基、テトラゾリル基、チアゾリル基、ピラゾリル基、オキサゾリル基、イソオキサゾリル基、イソチアゾリル基、フラザニル基、チアジアゾリル基、オキサジアゾリル基、ピリジル基、ピラジニル基、ピリダジニル基、ピリミジニル基、トリアジニル基、プリニル基、プテリジニル基、キノリル基、イソキノリル基、ナフチリジニル基、キノキサリニル基、シンノリニル基、キナゾリニル基、フタラジニル基、イミダゾピリジル基、イミダゾチアゾリル基、イミダゾオキサゾリル基、ベンゾチアゾリル基、ベンゾオキサゾリル基、ベンズイミダゾリル基、インドリル基、イソインドリル基、インダゾリル基、ピロロピリジル基、チエノピリジル基、フロピリジル基、ベンゾチアジアゾリル基、ベンゾオキサジアゾリル基、ピリドピリミジニル基、ベンゾフリル基、ベンゾチエニル基、チエノフリル基などがあげられる。 The “5- to 10-membered heteroaryl group” is an aromatic cyclic group having 5 to 10 atoms constituting the ring and containing 1 to 5 heteroatoms in the atoms constituting the ring. Specific examples include furyl, thienyl, pyrrolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, isothiazolyl, furazanyl, thiadiazolyl, oxadiazolyl Group, pyridyl group, pyrazinyl group, pyridazinyl group, pyrimidinyl group, triazinyl group, purinyl group, pteridinyl group, quinolyl group, isoquinolyl group, naphthyridinyl group, quinoxalinyl group, cinnolinyl group, quinazolinyl group, phthalazinyl group, imidazopyridyl group, imidazothia group Zolyl group, imidazooxazo Group, benzothiazolyl group, benzoxazolyl group, benzimidazolyl group, indolyl group, isoindolyl group, indazolyl group, pyrrolopyridyl group, thienopyridyl group, furopyridyl group, benzothiadiazolyl group, benzooxadiazolyl group, pyridopyrimidinyl group Benzofuryl group, benzothienyl group, thienofuryl group and the like.
　「５～１０員ヘテロアリール基」の好適な例としては、フリル基、チエニル基、ピロリル基、イミダゾリル基、チアゾリル基、ピラゾリル基、オキサゾリル基、イソオキサゾリル基、イソチアゾリル基、ピリジル基、ピリミジニル基をあげることができる。 Preferable examples of the “5- to 10-membered heteroaryl group” include furyl group, thienyl group, pyrrolyl group, imidazolyl group, thiazolyl group, pyrazolyl group, oxazolyl group, isoxazolyl group, isothiazolyl group, pyridyl group, and pyrimidinyl group. be able to.
　「３～１０員非芳香族ヘテロ環式基」とは、
（１）環を構成する原子の数が３ないし１０個であり、
（２）環を構成する原子中に１ないし２個のヘテロ原子を含有し、
（３）環中に重結合を１ないし２個含んでいてもよく、
（４）環中にカルボニル基、スルフィニル基またはスルホニル基を１ないし３個含んでいてもよい、
（５）単環式または二環式である非芳香族性の環式基を意味し、環を構成する原子中に窒素原子を含有する場合、窒素原子から結合手が出ていてもよい。具体例としては、アジリジニル基、アゼチジニル基、ピロリジニル基、ピペリジニル基、アゼパニル基、アゾカニル基、ピペラジニル基、ジアゼパニル基、ジアゾカニル基、ジアザビシクロ[２．２．１]ヘプチル基、モルホリニル基、チオモルホリニル基、１，１－ジオキソチオモルホリニル基、オキシラニル基、オキセタニル基、テトラヒドロフリル基、テトラヒドロピラニル基、ジオキサニル基、テトラヒドロチエニル基、テトラヒドロチオピラニル基、オキサゾリジニル基、チアゾリジニル基などがあげられる。 “3- to 10-membered non-aromatic heterocyclic group” means
(1) The number of atoms constituting the ring is 3 to 10,
(2) containing 1 to 2 heteroatoms in the atoms constituting the ring;
(3) The ring may contain 1 to 2 heavy bonds,
(4) The ring may contain 1 to 3 carbonyl groups, sulfinyl groups or sulfonyl groups.
(5) A non-aromatic cyclic group which is monocyclic or bicyclic, and when a nitrogen atom is contained in the atoms constituting the ring, a bond may be taken out from the nitrogen atom. Specific examples include aziridinyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, azepanyl group, azocanyl group, piperazinyl group, diazepanyl group, diazocanyl group, diazabicyclo [2.2.1] heptyl group, morpholinyl group, thiomorpholinyl group, 1 1,1-dioxothiomorpholinyl group, oxiranyl group, oxetanyl group, tetrahydrofuryl group, tetrahydropyranyl group, dioxanyl group, tetrahydrothienyl group, tetrahydrothiopyranyl group, oxazolidinyl group, thiazolidinyl group and the like.
　「３～１０員非芳香族ヘテロ環式基」の好適な例としては、アジリジニル基、アゼチジニル基、ピロリジニル基、ピペリジニル基、アゼパニル基、ピペラジニル基、ジアゼパニル基、モルホリニル基、チオモルホリニル基、１，１－ジオキソチオモルホリニル基、テトラヒドロフリル基、テトラヒドロピラニル基をあげることができる。 Suitable examples of the “3- to 10-membered non-aromatic heterocyclic group” include aziridinyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, azepanyl group, piperazinyl group, diazepanyl group, morpholinyl group, thiomorpholinyl group, 1,1 -A dioxothiomorpholinyl group, a tetrahydrofuryl group and a tetrahydropyranyl group can be mentioned.
　「４～１０員非芳香族ヘテロ環式基」とは、
（１）環を構成する原子の数が４ないし１０個であり、
（２）環を構成する原子中に１ないし２個のヘテロ原子を含有し、
（３）環中に二重結合を１ないし２個含んでいてもよく、
（４）環中にカルボニル基、スルフィニル基またはスルホニル基を１ないし３個含んでいてもよい、
（５）単環式または二環式である非芳香族性の環式基を意味し、環を構成する原子中に窒素原子を含有する場合、窒素原子から結合手が出ていてもよい。具体例としては、アゼチジニル基、ピロリジニル基、ピペリジニル基、アゼパニル基、アゾカニル基、ピペラジニル基、ジアゼパニル基、ジアゾカニル基、ジアザビシクロ[２．２．１]ヘプチル基、モルホリニル基、チオモルホリニル基、１，１－ジオキソチオモルホリニル基、オキセタニル基、テトラヒドロフリル基、テトラヒドロピラニル基、ジオキサニル基、テトラヒドロチエニル基、テトラヒドロチオピラニル基、オキサゾリジニル基、チアゾリジニル基などがあげられる。 “4- to 10-membered non-aromatic heterocyclic group” means
(1) The number of atoms constituting the ring is 4 to 10,
(2) containing 1 to 2 heteroatoms in the atoms constituting the ring;
(3) The ring may contain 1 to 2 double bonds,
(4) The ring may contain 1 to 3 carbonyl groups, sulfinyl groups or sulfonyl groups.
(5) A non-aromatic cyclic group which is monocyclic or bicyclic, and when a nitrogen atom is contained in the atoms constituting the ring, a bond may be taken out from the nitrogen atom. Specific examples include azetidinyl group, pyrrolidinyl group, piperidinyl group, azepanyl group, azocanyl group, piperazinyl group, diazepanyl group, diazocanyl group, diazabicyclo [2.2.1] heptyl group, morpholinyl group, thiomorpholinyl group, 1,1- Examples thereof include a dioxothiomorpholinyl group, an oxetanyl group, a tetrahydrofuryl group, a tetrahydropyranyl group, a dioxanyl group, a tetrahydrothienyl group, a tetrahydrothiopyranyl group, an oxazolidinyl group, and a thiazolidinyl group.
　「４～１０員非芳香族ヘテロ環式基」の好適な例としては、アゼチジニル基、ピロリジニル基、ピペリジニル基、アゼパニル基、ピペラジニル基、ジアゼパニル基、モルホリニル基、チオモルホリニル基、１，１－ジオキソチオモルホリニル基、テトラヒドロフリル基、テトラヒドロピラニル基をあげることができる。 Preferable examples of the “4- to 10-membered non-aromatic heterocyclic group” include azetidinyl group, pyrrolidinyl group, piperidinyl group, azepanyl group, piperazinyl group, diazepanyl group, morpholinyl group, thiomorpholinyl group, 1,1-dioxo Examples thereof include a thiomorpholinyl group, a tetrahydrofuryl group, and a tetrahydropyranyl group.
　「Ｃ３－１０シクロアルキルＣ１－６アルキル基」とは、上記定義「Ｃ１－６アルキル基」中の任意の水素原子を、上記定義「Ｃ３－１０シクロアルキル基」で置換した基を意味し、具体例としては、シクロプロピルメチル基、シクロブチルメチル基、シクロペンチルメチル基、シクロヘキシルメチル基、シクロヘプチルメチル基、シクロオクチルメチル基、シクロノニルメチル基、シクロデシルメチル基、ビシクロ[２．２．１]ヘプチルメチル基（ノルボルニルメチル基）、ビシクロ[４．４．０]デシルメチル基（デカリルメチル基）などがあげられる。 The "C 3-10 cycloalkyl C 1-6 alkyl group", any hydrogen atom in the definition of "C 1-6 alkyl group", was replaced with the above defined "C 3-10 cycloalkyl group" group Specific examples include cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, cyclooctylmethyl group, cyclononylmethyl group, cyclodecylmethyl group, bicyclo [2 2.1] heptylmethyl group (norbornylmethyl group), bicyclo [4.4.0] decylmethyl group (decalylmethyl group), and the like.
　「Ｃ６－１０アリールＣ１－６アルキル基」とは、上記定義「Ｃ１－６アルキル基」中の任意の水素原子を、上記定義「Ｃ６－１０アリール基」で置換した基を意味し、具体例としては、ベンジル基、１－ナフチルメチル基、２－ナフチルメチル基、フェネチル基、１－ナフチルエチル基、２－ナフチルエチル基などがあげられる。 “C 6-10 aryl C 1-6 alkyl group” means a group in which any hydrogen atom in the above-defined “C 1-6 alkyl group” is substituted with the above-defined “C 6-10 aryl group” Specific examples include a benzyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, phenethyl group, 1-naphthylethyl group, 2-naphthylethyl group and the like.
　「５～１０員へテロアリールＣ１－６アルキル基」とは、上記定義「Ｃ１－６アルキル基」中の任意の水素原子を、上記定義「５～１０員ヘテロアリール基」で置換した基を意味し、具体例としては、フリルメチル基、チエニルメチル基、ピロリルメチル基、イミダゾリルメチル基、トリアゾリルメチル基、テトラゾリルメチル基、チアゾリルメチル基、ピラゾリルメチル基、オキサゾリルメチル基、イソオキサゾリルメチル基、イソチアゾリルメチル基、フラザニルメチル基、チアジアゾリルメチル基、オキサジアゾリルメチル基、ピリジルメチル基、ピラジニルメチル基、ピリダジニルメチル基、ピリミジニルメチル基、トリアジニルメチル基、フリルエチル基、チエニルエチル基、ピロリルエチル基、イミダゾリルエチル基、トリアゾリルエチル基、テトラゾリルエチル基、チアゾリルエチル基、ピラゾリルエチル基、オキサゾリルエチル基、イソオキサゾリルエチル基、イソチアゾリルエチル基、フラザニルエチル基、チアジアゾリルエチル基、オキサジアゾリルエチル基、ピリジルエチル基、ピラジニルエチル基、ピリダジニルエチル基、ピリミジニルエチル基、トリアジニルエチル基などがあげられる。 The “5- to 10-membered heteroaryl C 1-6 alkyl group” is a group in which any hydrogen atom in the above-defined “C 1-6 alkyl group” is substituted with the above-defined “5- to 10-membered heteroaryl group” Specific examples include furylmethyl, thienylmethyl, pyrrolylmethyl, imidazolylmethyl, triazolylmethyl, tetrazolylmethyl, thiazolylmethyl, pyrazolylmethyl, oxazolylmethyl, iso Oxazolylmethyl, isothiazolylmethyl, furazanylmethyl, thiadiazolylmethyl, oxadiazolylmethyl, pyridylmethyl, pyrazinylmethyl, pyridazinylmethyl, pyrimidinylmethyl, triazinylmethyl , Furylethyl group, thienylethyl group, pyrrolylethyl group, imidazolylethyl group, tria Rylethyl group, tetrazolylethyl group, thiazolylethyl group, pyrazolylethyl group, oxazolylethyl group, isoxazolylethyl group, isothiazolylethyl group, furazanylethyl group, thiadiazolylethyl group, oxadiazolylethyl group, Examples include pyridylethyl group, pyrazinylethyl group, pyridazinylethyl group, pyrimidinylethyl group, triazinylethyl group and the like.
　「５～１０員ヘテロアリールＣ１－６アルキル基」の好適な例としては、フリルメチル基、チエニルメチル基、ピロリルメチル基、イミダゾリルメチル基、チアゾリルメチル基、ピラゾリルメチル基、オキサゾリルメチル基、イソオキサゾリルメチル基、イソチアゾリルメチル基、ピリジルメチル基、ピリミジニルメチル基、フリルエチル基、チエニルエチル基、ピロリルエチル基、イミダゾリルエチル基、チアゾリルエチル基、ピラゾリルエチル基、オキサゾリルエチル基、イソオキサゾリルエチル基、イソチアゾリルエチル基、ピリジルエチル基、ピリミジニルエチル基をあげることができる。 Preferable examples of “5- to 10-membered heteroaryl C 1-6 alkyl group” include furylmethyl group, thienylmethyl group, pyrrolylmethyl group, imidazolylmethyl group, thiazolylmethyl group, pyrazolylmethyl group, oxazolylmethyl group, iso Oxazolylmethyl, isothiazolylmethyl, pyridylmethyl, pyrimidinylmethyl, furylethyl, thienylethyl, pyrrolylethyl, imidazolylethyl, thiazolylethyl, pyrazolylethyl, oxazolylethyl, isoxa Examples thereof include a zolylethyl group, an isothiazolylethyl group, a pyridylethyl group, and a pyrimidinylethyl group.
　「３～１０員非芳香族ヘテロ環Ｃ１－６アルキル基」とは、上記定義「Ｃ１－６アルキル基」中の任意の水素原子を、上記定義「３～１０員非芳香族ヘテロ環式基」で置換した基を意味し、具体例としては、アジリジニルメチル基、アゼチジニルメチル基、ピロリジニルメチル基、ピペリジニルメチル基、アゼパニルメチル基、アゾカニルメチル基、ピペラジニルメチル基、ジアゼパニルメチル基、ジアゾカニルメチル基、モルホリニルメチル基、チオモルホリニルメチル基、１，１－ジオキソチオモルホリニルメチル基、オキシラニルメチル基、オキセタニルメチル基、テトラヒドロフリルメチル基、テトラヒドロピラニルメチル基、ジオキサニルメチル基、テトラヒドロチエニルメチル基、テトラヒドロチオピラニルメチル基、オキサゾリジニルメチル基、チアゾリジニルメチル基、アジリジニルエチル基、アゼチジニルエチル基、ピロリジニルエチル基、ピペリジニルエチル基、アゼパニルエチル基、アゾカニルエチル基、ピペラジニルエチル基、ジアゼパニルエチル基、ジアゾカニルエチル基、モルホリニルエチル基、チオモルホリニルエチル基、１，１－ジオキソチオモルホリニルエチル基、オキシラニルエチル基、オキセタニルエチル基、テトラヒドロフリルエチル基、テトラヒドロピラニルエチル基、ジオキサニルエチル基、テトラヒドロチエニルエチル基、テトラヒドロチオピラニルエチル基、オキサゾリジニルエチル基、チアゾリジニルエチル基などがあげられる。 “3- to 10-membered non-aromatic heterocyclic C 1-6 alkyl group” means any hydrogen atom in the above-defined “C 1-6 alkyl group” as defined in the above-mentioned “3- to 10-membered non-aromatic heterocyclic ring”. A group substituted by the formula group, and specific examples include aziridinylmethyl group, azetidinylmethyl group, pyrrolidinylmethyl group, piperidinylmethyl group, azepanylmethyl group, azocanylmethyl group, piperazinylmethyl Group, diazepanylmethyl group, diazocanylmethyl group, morpholinylmethyl group, thiomorpholinylmethyl group, 1,1-dioxothiomorpholinylmethyl group, oxiranylmethyl group, oxetanylmethyl group Tetrahydrofurylmethyl group, tetrahydropyranylmethyl group, dioxanylmethyl group, tetrahydrothienylmethyl group, tetrahydrothiopyranylmethyl group, oxa Lydinylmethyl group, thiazolidinylmethyl group, aziridinylethyl group, azetidinylethyl group, pyrrolidinylethyl group, piperidinylethyl group, azepanylethyl group, azocanylethyl group, piperazinylethyl group, diazepanyl Ethyl group, diazocanylethyl group, morpholinylethyl group, thiomorpholinylethyl group, 1,1-dioxothiomorpholinylethyl group, oxiranylethyl group, oxetanylethyl group, tetrahydrofurylethyl group, Examples thereof include a tetrahydropyranylethyl group, a dioxanylethyl group, a tetrahydrothienylethyl group, a tetrahydrothiopyranylethyl group, an oxazolidinylethyl group, and a thiazolidinylethyl group.
　「３～１０員非芳香族ヘテロ環Ｃ１－６アルキル基」の好適な例としては、アゼチジニルメチル基、ピロリジニルメチル基、ピペリジニルメチル基、アゼパニルメチル基、ピペラジニルメチル基、ジアゼパニルメチル基、モルホリニルメチル基、チオモルホリニルメチル基、テトラヒドロフリルメチル基、アゼチジニルエチル基、ピロリジニルエチル基、ピペリジニルエチル基、アゼパニルエチル基、ピペラジニルエチル基、ジアゼパニルエチル基、モルホリニルエチル基、チオモルホリニルエチル基、テトラヒドロフリルエチル基をあげることができる。 Preferable examples of “3 to 10-membered non-aromatic heterocyclic C 1-6 alkyl group” include azetidinylmethyl group, pyrrolidinylmethyl group, piperidinylmethyl group, azepanylmethyl group, piperazinylmethyl group , Diazepanylmethyl group, morpholinylmethyl group, thiomorpholinylmethyl group, tetrahydrofurylmethyl group, azetidinylethyl group, pyrrolidinylethyl group, piperidinylethyl group, azepanylethyl group, piperazinyl Examples thereof include an ethyl group, a diazepanylethyl group, a morpholinylethyl group, a thiomorpholinylethyl group, and a tetrahydrofurylethyl group.
　「Ｃ１－６アルコキシ基」とは、上記定義「Ｃ１－６アルキル基」の末端に酸素原子が結合した基であることを意味し、具体的としては、メトキシ基、エトキシ基、１－プロポキシ基（ｎ－プロポキシ基）、２－プロポキシ基（ｉ－プロポキシ基）、２－メチル－１－プロポキシ基（ｉ－ブトキシ基）、２－メチル－２－プロポキシ基（ｔ－ブトキシ基）、１－ブトキシ基（ｎ－ブトキシ基）、２－ブトキシ基（ｓ－ブトキシ基）、１－ペンチルオキシ基、２－ペンチルオキシ基、３－ペンチルオキシ基、２－メチル－１－ブトキシ基、３－メチル－１－ブトキシ基、２－メチル－２－ブトキシ基、３－メチル－２－ブトキシ基、２，２－ジメチル－１－プロポキシ基、１－へキシルオキシ基、２－へキシルオキシ基、３－へキシルオキシ基、２－メチル－１－ペンチルオキシ基、３－メチル－１－ペンチルオキシ基、４－メチル－１－ペンチルオキシ基、２－メチル－２－ペンチルオキシ基、３－メチル－２－ペンチルオキシ基、４－メチル－２－ペンチルオキシ基、２－メチル－３－ペンチルオキシ基、３－メチル－３－ペンチルオキシ基、２，３－ジメチル－１－ブトキシ基、３，３－ジメチル－１－ブトキシ基、２，２－ジメチル－１－ブトキシ基、２－エチル－１－ブトキシ基、３，３－ジメチル－２－ブトキシ基、２，３－ジメチル－２－ブトキシ基などがあげられる。 The “C 1-6 alkoxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 1-6 alkyl group”, and specifically includes a methoxy group, an ethoxy group, 1- Propoxy group (n-propoxy group), 2-propoxy group (i-propoxy group), 2-methyl-1-propoxy group (i-butoxy group), 2-methyl-2-propoxy group (t-butoxy group), 1-butoxy group (n-butoxy group), 2-butoxy group (s-butoxy group), 1-pentyloxy group, 2-pentyloxy group, 3-pentyloxy group, 2-methyl-1-butoxy group, 3 -Methyl-1-butoxy group, 2-methyl-2-butoxy group, 3-methyl-2-butoxy group, 2,2-dimethyl-1-propoxy group, 1-hexyloxy group, 2-hexyloxy group, 3 -Hexyloxy 2-methyl-1-pentyloxy group, 3-methyl-1-pentyloxy group, 4-methyl-1-pentyloxy group, 2-methyl-2-pentyloxy group, 3-methyl-2-pentyloxy group 4-methyl-2-pentyloxy group, 2-methyl-3-pentyloxy group, 3-methyl-3-pentyloxy group, 2,3-dimethyl-1-butoxy group, 3,3-dimethyl-1- Examples include butoxy, 2,2-dimethyl-1-butoxy, 2-ethyl-1-butoxy, 3,3-dimethyl-2-butoxy, 2,3-dimethyl-2-butoxy, and the like.
　「Ｃ１－６アルキルチオ基」とは、上記定義「Ｃ１－６アルキル基」の末端に硫黄原子が結合した基であることを意味し、具体例としては、メチルチオ基、エチルチオ基、１－プロピルチオ基（ｎ－プロピルチオ基）、２－プロピルチオ基（ｉ－プロピルチオ基）、２－メチル－１－プロピルチオ基（ｉ－ブチルチオ基）、２－メチル－２－プロピルチオ基（ｔ－ブチルチオ基）、１－ブチルチオ基（ｎ－ブチルチオ基）、２－ブチルチオ基（ｓ－ブチルチオ基）、１－ペンチルチオ基、２－ペンチルチオ基、３－ペンチルチオ基、２－メチル－１－ブチルチオ基、３－メチル－１－ブチルチオ基、２－メチル－２－ブチルチオ基、３－メチル－２－ブチルチオ基、２，２－ジメチル－１－プロピルチオ基、１－へキシルチオ基、２－へキシルチオ基、３－へキシルチオ基、２－メチル－１－ペンチルチオ基、３－メチル－１－ペンチルチオ基、４－メチル－１－ペンチルチオ基、２－メチル－２－ペンチルチオ基、３－メチル－２－ペンチルチオ基、４－メチル－２－ペンチルチオ基、２－メチル－３－ペンチルチオ基、３－メチル－３－ペンチルチオ基、２，３－ジメチル－１－ブチルチオ基、３，３－ジメチル－１－ブチルチオ基、２，２－ジメチル－１－ブチルチオ基、２－エチル－１－ブチルチオ基、３，３－ジメチル－２－ブチルチオ基、２，３－ジメチル－２－ブチルチオ基などがあげられる。 The “C 1-6 alkylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 1-6 alkyl group”. Specific examples thereof include a methylthio group, an ethylthio group, a 1- Propylthio group (n-propylthio group), 2-propylthio group (i-propylthio group), 2-methyl-1-propylthio group (i-butylthio group), 2-methyl-2-propylthio group (t-butylthio group), 1-butylthio group (n-butylthio group), 2-butylthio group (s-butylthio group), 1-pentylthio group, 2-pentylthio group, 3-pentylthio group, 2-methyl-1-butylthio group, 3-methyl- 1-butylthio group, 2-methyl-2-butylthio group, 3-methyl-2-butylthio group, 2,2-dimethyl-1-propylthio group, 1-hexylthio group, 2-hexyl group Ruthio group, 3-hexylthio group, 2-methyl-1-pentylthio group, 3-methyl-1-pentylthio group, 4-methyl-1-pentylthio group, 2-methyl-2-pentylthio group, 3-methyl-2 -Pentylthio group, 4-methyl-2-pentylthio group, 2-methyl-3-pentylthio group, 3-methyl-3-pentylthio group, 2,3-dimethyl-1-butylthio group, 3,3-dimethyl-1- Examples thereof include a butylthio group, a 2,2-dimethyl-1-butylthio group, a 2-ethyl-1-butylthio group, a 3,3-dimethyl-2-butylthio group, and a 2,3-dimethyl-2-butylthio group.
　「Ｃ３－６アルケニルオキシ基」とは、上記定義「Ｃ３－６アルケニル基」の末端に酸素原子が結合した基であることを意味し、具体的には例えば、２－プロペニルオキシ基（アリルオキシ基）、２－ブテニルオキシ基、３－ブテニルオキシ基、ペンテニルオキシ基、ヘキセニルオキシ基などがあげられる。 The “C 3-6 alkenyloxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 3-6 alkenyl group”. Specifically, for example, a 2-propenyloxy group ( Allyloxy group), 2-butenyloxy group, 3-butenyloxy group, pentenyloxy group, hexenyloxy group and the like.
　「Ｃ３－６アルケニルチオ基」とは、上記定義「Ｃ３－６アルケニル基」の末端に硫黄原子が結合した基であることを意味し、具体例としては、具体例としては、２－プロペニルチオ基（アリルチオ基）、２－ブテニルチオ基、３－ブテニルチオ基、ペンテニルチオ基、ヘキセニルチオ基などがあげられる。 The “C 3-6 alkenylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 3-6 alkenyl group”. As a specific example, a specific example includes 2- Examples include propenylthio group (allylthio group), 2-butenylthio group, 3-butenylthio group, pentenylthio group, hexenylthio group and the like.
　「Ｃ３－６アルキニルオキシ基」とは、上記定義「Ｃ３－６アルキニル基」の末端に酸素原子が結合した基であることを意味し、具体例としては、２－プロピニルオキシ基、２－ブチニルオキシ基、３－ブチニルオキシ基、ペンチニルオキシ基、ヘキシニルオキシ基などがあげられる。 The “C 3-6 alkynyloxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 3-6 alkynyl group”. Specific examples include a 2-propynyloxy group, -Butynyloxy group, 3-butynyloxy group, pentynyloxy group, hexynyloxy group and the like.
　「Ｃ３－６アルキニルチオ基」とは、上記定義「Ｃ３－６アルキニル基」の末端に硫黄原子が結合した基であることを意味し、具体例としては、２－プロピニルチオ基、２－ブチニルチオ基、３－ブチニルチオ基、ペンチニルチオ基、ヘキシニルチオ基などがあげられる。 The “C 3-6 alkynylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 3-6 alkynyl group”. Specific examples include a 2-propynylthio group, 2 -Butynylthio group, 3-butynylthio group, pentynylthio group, hexynylthio group and the like.
　「Ｃ３－１０シクロアルコキシ基」とは、上記定義「Ｃ３－１０シクロアルキル基」の末端に酸素原子が結合した基であることを意味し、具体例としては、シクロプロポキシ基、シクロブトキシ基、シクロペンチルオキシ基、シクロヘキシルオキシ基、シクロヘプチルオキシ基、シクロオクチルオキシ基などがあげられる。 “C 3-10 cycloalkoxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 3-10 cycloalkyl group”. Specific examples thereof include a cyclopropoxy group, cyclobutoxy group, and the like. Group, cyclopentyloxy group, cyclohexyloxy group, cycloheptyloxy group, cyclooctyloxy group and the like.
　「Ｃ３－１０シクロアルキルチオ基」とは、上記定義「Ｃ３－１０シクロアルキル基」の末端に硫黄原子が結合した基であることを意味し、具体例としては、シクロプロピルチオ基、シクロブチルチオ基、シクロペンチルチオ基、シクロヘキシルチオ基、シクロヘプチルチオ基、シクロオクチルチオ基などがあげられる。 The “C 3-10 cycloalkylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “C 3-10 cycloalkyl group”. Specific examples include a cyclopropylthio group, a cyclopropyl group, Examples thereof include a butylthio group, a cyclopentylthio group, a cyclohexylthio group, a cycloheptylthio group, and a cyclooctylthio group.
　「Ｃ６－１０アリールオキシ基」とは、上記定義「Ｃ６－１０アリール基」の末端に酸素原子が結合した基であることを意味し、具体例としては、フェノキシ基、１－ナフトキシ基、２－ナフトキシ基、インデニルオキシ基、アズレニルオキシ基、ヘプタレニルオキシ基などがあげられる。 The “C 6-10 aryloxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “C 6-10 aryl group”. Specific examples thereof include a phenoxy group and a 1-naphthoxy group. 2-naphthoxy group, indenyloxy group, azulenyloxy group, heptalenyloxy group and the like.
　「Ｃ６－１０アリールチオ基」とは、上記定義「Ｃ６－１０アリール基」の末端に硫黄原子が結合した基であることを意味し、具体例としては、フェニルチオ基、１－ナフチルチオ基、２－ナフチルチオ基、インデニルチオ基、アズレニルチオ基、ヘプタレニルチオ基などがあげられる。 The “C 6-10 arylthio group” means a group having a sulfur atom bonded to the end of the above-defined “C 6-10 aryl group”. Specific examples thereof include a phenylthio group, a 1-naphthylthio group, A 2-naphthylthio group, an indenylthio group, an azulenylthio group, a heptalenylthio group and the like can be mentioned.
　「５～１０員ヘテロアリールオキシ基」とは、上記定義「５～１０員ヘテロアリール基」の末端に酸素原子が結合した基であることを意味し、具体例としては、フリルオキシ基、チエニルオキシ基、ピロリルオキシ基、イミダゾリルオキシ基、トリアゾリルオキシ基、チアゾリルオキシ基、ピラゾリルオキシ基、オキサゾリルオキシ基、イソオキサゾリルオキシ基、イソチアゾリルオキシ基、フラザニルオキシ基、チアジアゾリルオキシ基、オキサジアゾリルオキシ基、ピリジルオキシ基、ピラジニルオキシ基、ピリダジニルオキシ基、ピリミジニルオキシ基、トリアジニルオキシ基などがあげられる。 The “5- to 10-membered heteroaryloxy group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “5- to 10-membered heteroaryl group”. Specific examples include a furyloxy group, thienyl. Oxy group, pyrrolyloxy group, imidazolyloxy group, triazolyloxy group, thiazolyloxy group, pyrazolyloxy group, oxazolyloxy group, isoxazolyloxy group, isothiazolyloxy group, furazanyloxy group, thiadiazolyloxy group, Examples thereof include an oxadiazolyloxy group, a pyridyloxy group, a pyrazinyloxy group, a pyridazinyloxy group, a pyrimidinyloxy group, and a triazinyloxy group.
　「５～１０員ヘテロアリールチオ基」とは、上記定義「５～１０員ヘテロアリール基」の末端に硫黄原子が結合した基であることを意味し、具体例としては、フリルチオ基、チエニルチオ基、ピロリルチオ基、イミダゾリルチオ基、トリアゾリルチオ基、チアゾリルチオ基、ピラゾリルチオ基、オキサゾリルチオ基、イソオキサゾリルチオ基、イソチアゾリルチオ基、フラザニルチオ基、チアジアゾリルチオ基、オキサジアゾリルチオ基、ピリジルチオ基、ピラジニルチオ基、ピリダジニルチオ基、ピリミジニルチオ基、トリアジニルチオ基などがあげられる。 The “5- to 10-membered heteroarylthio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “5- to 10-membered heteroaryl group”. Specific examples include a furylthio group and a thienylthio group. , Pyrrolylthio group, imidazolylthio group, triazolylthio group, thiazolylthio group, pyrazolylthio group, oxazolylthio group, isoxazolylthio group, isothiazolylthio group, furazanylthio group, thiadiazolylthio group, oxadiazolylthio group, pyridylthio group , Pyrazinylthio group, pyridazinylthio group, pyrimidinylthio group, triazinylthio group and the like.
　「４～１０員非芳香族ヘテロ環オキシ基」とは、上記定義「４～１０員非芳香族ヘテロ環式基」の末端に酸素原子が結合した基であることを意味し、具体例としては、アゼチジニルオキシ基、ピロリジニルオキシ基、ピペリジニルオキシ基、アゼパニルオキシ基、アゾカニルオキシ基、ピペラジニルオキシ基、ジアゼパニルオキシ基、ジアゾカニルオキシ基、モルホリニルオキシ基、チオモルホリニルオキシ基、１，１－ジオキソチオモルホリニルオキシ基、オキセタニルオキシ基、テトラヒドロフリルオキシ基、テトラヒドロピラニルオキシ基、テトラヒドロチエニルオキシ基、テトラヒドロチオピラニルオキシ基などがあげられる。 “4- to 10-membered non-aromatic heterocyclic group” means a group in which an oxygen atom is bonded to the terminal of the above-defined “4- to 10-membered non-aromatic heterocyclic group”. Is an azetidinyloxy group, pyrrolidinyloxy group, piperidinyloxy group, azepanyloxy group, azocanyloxy group, piperazinyloxy group, diazepanyloxy group, diazocanyloxy group, morpholinyloxy group Thiomorpholinyloxy group, 1,1-dioxothiomorpholinyloxy group, oxetanyloxy group, tetrahydrofuryloxy group, tetrahydropyranyloxy group, tetrahydrothienyloxy group, tetrahydrothiopyranyloxy group, etc. It is done.
　「４～１０員非芳香族ヘテロ環チオ基」とは、上記定義「４～１０員非芳香族ヘテロ環式基」の末端に硫黄原子が結合した基であることを意味し、具体例としては、アゼチジニルチオ基、ピロリジニルチオ基、ピペリジニルチオ基、アゼパニルチオ基、アゾカニルチオ基、ピペラジニルチオ基、ジアゼパニルチオ基、ジアゾカニルチオ基、オキセタニルチオ基、テトラヒドロフリルチオ基、テトラヒドロピラニルチオ基、テトラヒドロチエニルチオ基、テトラヒドロチオピラニルチオ基などがあげられる。 The “4- to 10-membered non-aromatic heterocyclic thio group” means a group in which a sulfur atom is bonded to the terminal of the above-defined “4- to 10-membered non-aromatic heterocyclic group”. Azetidinylthio group, pyrrolidinylthio group, piperidinylthio group, azepanylthio group, azocanylthio group, piperazinylthio group, diazepanylthio group, diazocanylthio group, oxetanylthio group, tetrahydrofurylthio group, tetrahydropyranylthio group, tetrahydrothienylthio group, tetrahydro And thiopyranylthio group.
　「モノ－Ｃ１－６アルキルアミノ基」とは、アミノ基中の１個の水素原子を、上記定義「Ｃ１－６アルキル基」で置換した基を意味し、具体例としては、メチルアミノ基、エチルアミノ基、１－プロピルアミノ基（ｎ－プロピルアミノ基）、２－プロピルアミノ基（ｉ－プロピルアミノ基）、２－メチル－１－プロピルアミノ基（ｉ－ブチルアミノ基）、２－メチル－２－プロピルアミノ基（ｔ－ブチルアミノ基）、１－ブチルアミノ基（ｎ－ブチルアミノ基）、２－ブチルアミノ基（ｓ－ブチルアミノ基）、１－ペンチルアミノ基、２－ペンチルアミノ基、３－ペンチルアミノ基、２－メチル－１－ブチルアミノ基、３－メチル－１－ブチルアミノ基、２－メチル－２－ブチルアミノ基、３－メチル－２－ブチルアミノ基、２，２－ジメチル－１－プロピルアミノ基、１－へキシルアミノ基、２－へキシルアミノ基、３－へキシルアミノ基、２－メチル－１－ペンチルアミノ基、３－メチル－１－ペンチルアミノ基、４－メチル－１－ペンチルアミノ基、２－メチル－２－ペンチルアミノ基、３－メチル－２－ペンチルアミノ基、４－メチル－２－ペンチルアミノ基、２－メチル－３－ペンチルアミノ基、３－メチル－３－ペンチルアミノ基、２，３－ジメチル－１－ブチルアミノ基、３，３－ジメチル－１－ブチルアミノ基、２，２－ジメチル－１－ブチルアミノ基、２－エチル－１－ブチルアミノ基、３，３－ジメチル－２－ブチルアミノ基、２，３－ジメチル－２－ブチルアミノ基などがあげられる。 “Mono-C 1-6 alkylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “C 1-6 alkyl group”. Specific examples include methylamino Group, ethylamino group, 1-propylamino group (n-propylamino group), 2-propylamino group (i-propylamino group), 2-methyl-1-propylamino group (i-butylamino group), 2 -Methyl-2-propylamino group (t-butylamino group), 1-butylamino group (n-butylamino group), 2-butylamino group (s-butylamino group), 1-pentylamino group, 2- Pentylamino group, 3-pentylamino group, 2-methyl-1-butylamino group, 3-methyl-1-butylamino group, 2-methyl-2-butylamino group, 3-methyl-2-butylamino group, 2,2-jime 1-hexylamino group, 1-hexylamino group, 2-hexylamino group, 3-hexylamino group, 2-methyl-1-pentylamino group, 3-methyl-1-pentylamino group, 4-methyl- 1-pentylamino group, 2-methyl-2-pentylamino group, 3-methyl-2-pentylamino group, 4-methyl-2-pentylamino group, 2-methyl-3-pentylamino group, 3-methyl- 3-pentylamino group, 2,3-dimethyl-1-butylamino group, 3,3-dimethyl-1-butylamino group, 2,2-dimethyl-1-butylamino group, 2-ethyl-1-butylamino group Group, 3,3-dimethyl-2-butylamino group, 2,3-dimethyl-2-butylamino group and the like.
　「モノ－Ｃ３－１０シクロアルキルアミノ基」とは、アミノ基中の１個の水素原子を、上記定義「Ｃ３－１０シクロアルキル基」で置換した基を意味し、具体例としては、シクロプロピルアミノ基、シクロブチルアミノ基、シクロペンチルアミノ基、シクロヘキシルアミノ基、シクロヘプチルアミノ基、シクロオクチルアミノ基などがあげられる。 “Mono-C 3-10 cycloalkylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “C 3-10 cycloalkyl group”. Examples thereof include a cyclopropylamino group, a cyclobutylamino group, a cyclopentylamino group, a cyclohexylamino group, a cycloheptylamino group, and a cyclooctylamino group.
　「モノ－Ｃ６－１０アリールアミノ基」とは、アミノ基中の１個の水素原子を、上記定義「Ｃ６－１０アリール基」で置換した基を意味し、具体例としては、フェニルアミノ基、１－ナフチルアミノ基、２－ナフチルアミノ基、インデニルアミノ基、アズレニルアミノ基、ヘプタレニルアミノ基などがあげられる。 “Mono-C 6-10 arylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “C 6-10 aryl group”. Specific examples include phenylamino Group, 1-naphthylamino group, 2-naphthylamino group, indenylamino group, azulenylamino group, heptalenylamino group and the like.
　「モノ－５～１０員へテロアリールアミノ基」とは、アミノ基中の１個の水素原子を、上記定義「５～１０員ヘテロアリール基」で置換した基を意味し、具体例としては、フリルアミノ基、チエニルアミノ基、ピロリルアミノ基、イミダゾリルアミノ基、トリアゾリルアミノ基、テトラゾリルアミノ基、チアゾリルアミノ基、ピラゾリルアミノ基、オキサゾリルアミノ基、イソオキサゾリルアミノ基、イソチアゾリルアミノ基、フラザニルアミノ基、チアジアゾリルアミノ基、オキサジアゾリルアミノ基、ピリジルアミノ基、ピラジニルアミノ基、ピリダジニルアミノ基、ピリミジニルアミノ基、トリアジニルアミノ基などがあげられる。 “Mono-5 to 10-membered heteroarylamino group” means a group in which one hydrogen atom in an amino group is substituted with the above-defined “5 to 10-membered heteroaryl group”. , Furylamino group, thienylamino group, pyrrolylamino group, imidazolylamino group, triazolylamino group, tetrazolylamino group, thiazolylamino group, pyrazolylamino group, oxazolylamino group, isoxazolylamino group, isothiazo Examples include a tolylamino group, a furazanylamino group, a thiadiazolylamino group, an oxadiazolylamino group, a pyridylamino group, a pyrazinylamino group, a pyridazinylamino group, a pyrimidinylamino group, and a triazinylamino group.
　「モノ－５～１０員ヘテロアリールアミノ基」の好適な例としては、フリルアミノ基、チエニルアミノ基、ピロリルアミノ基、イミダゾリルアミノ基、チアゾリルアミノ基、ピラゾリルアミノ基、オキサゾリルアミノ基、イソオキサゾリルアミノ基、イソチアゾリルアミノ基、ピリジルアミノ基、ピリミジニルアミノ基をあげることができる。 Suitable examples of the “mono-5 to 10-membered heteroarylamino group” include a furylamino group, a thienylamino group, a pyrrolylamino group, an imidazolylamino group, a thiazolylamino group, a pyrazolylamino group, an oxazolylamino group, and an isoxazolyl group. Examples thereof include a ruamino group, an isothiazolylamino group, a pyridylamino group, and a pyrimidinylamino group.
　「モノ－４～１０員非芳香族ヘテロ環アミノ基」とは、アミノ基中の１個の水素原子を、上記定義「４～１０員非芳香族ヘテロ環式基」で置換した基を意味し、具体例としては、アゼチジニルアミノ基、ピロリジニルアミノ基、ピペリジニルアミノ基、アゼパニルアミノ基、アゾカニルアミノ基、ピペラジニルアミノ基、ジアゼパニルアミノ基、ジアゾカニルアミノ基、モルホリニルアミノ基、チオモルホリニルアミノ基、１，１－ジオキソチオモルホリニルアミノ基、オキセタニルアミノ基、テトラヒドロフリルアミノ基、テトラヒドロピラニルアミノ基、テトラヒドロチエニルアミノ基、テトラヒドロチオピラニルアミノ基などがあげられる。 “Mono-4 to 10-membered non-aromatic heterocyclic amino group” means a group in which one hydrogen atom in the amino group is substituted with the above-mentioned “4 to 10-membered non-aromatic heterocyclic group” Specific examples include azetidinylamino group, pyrrolidinylamino group, piperidinylamino group, azepanylamino group, azocanylamino group, piperazinylamino group, diazepanylamino group, diazocanylamino group, Morpholinylamino group, thiomorpholinylamino group, 1,1-dioxothiomorpholinylamino group, oxetanylamino group, tetrahydrofurylamino group, tetrahydropyranylamino group, tetrahydrothienylamino group, tetrahydrothiopyranyl An amino group etc. are mention | raise | lifted.
　「モノ－４～１０員非芳香族ヘテロ環アミノ基」の好適な例としては、ピロリジニルアミノ基、ピペリジニルアミノ基、アゼパニルアミノ基、ピペラジニルアミノ基、ジアゼパニルアミノ基、モルホリニルアミノ基、チオモルホリニルアミノ基、テトラヒドロフリルアミノ基をあげることができる。 Suitable examples of the “mono-4 to 10-membered non-aromatic heterocyclic amino group” include pyrrolidinylamino group, piperidinylamino group, azepanylamino group, piperazinylamino group, diazepanylamino group, Examples thereof include a morpholinylamino group, a thiomorpholinylamino group, and a tetrahydrofurylamino group.
　「ジ－Ｃ１－６アルキルアミノ基」とは、アミノ基中の２個の水素原子を、それぞれ同一のまたは異なる、上記定義「Ｃ１－６アルキル基」で置換した基を意味し、具体例としては、Ｎ，Ｎ－ジメチルアミノ基、Ｎ，Ｎ－ジエチルアミノ基、Ｎ，Ｎ－ジ－ｎ－プロピルアミノ基、Ｎ，Ｎ－ジ－ｉ－プロピルアミノ基、Ｎ，Ｎ－ジ－ｎ－ブチルアミノ基、Ｎ，Ｎ－ジ－ｉ－ブチルアミノ基、Ｎ，Ｎ－ジ－ｓ－ブチルアミノ基、Ｎ，Ｎ－ジ－ｔ－ブチルアミノ基、Ｎ－エチル－Ｎ－メチルアミノ基、Ｎ－ｎ－プロピル－Ｎ－メチルアミノ基、Ｎ－ｉ－プロピル－Ｎ－メチルアミノ基、Ｎ－ｎ－ブチル－Ｎ－メチルアミノ基、Ｎ－ｉ－ブチル－Ｎ－メチルアミノ基、Ｎ－ｓ－ブチル－Ｎ－メチルアミノ基、Ｎ－ｔ－ブチル－Ｎ－メチルアミノ基などがあげられる。 The "di -C 1-6 alkylamino group", the two hydrogen atoms in an amino group, each same or different, means a group obtained by substituting the above-defined "C 1-6 alkyl group", specifically Examples include N, N-dimethylamino group, N, N-diethylamino group, N, N-di-n-propylamino group, N, N-di-i-propylamino group, N, N-di-n. -Butylamino group, N, N-di-i-butylamino group, N, N-di-s-butylamino group, N, N-di-t-butylamino group, N-ethyl-N-methylamino group Nn-propyl-N-methylamino group, Ni-propyl-N-methylamino group, Nn-butyl-N-methylamino group, Ni-butyl-N-methylamino group, N -S-butyl-N-methylamino group, Nt-butyl-N-methylamino group And the like.
　以下に、上記一般式（Ｉ）で示される、本発明に係る化合物における各置換基について説明する。 Hereinafter, each substituent in the compound according to the present invention represented by the general formula (I) will be described.
［Ｒ１の意義］
　Ｒ１は、３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）または式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、同一または異なって、水素原子、Ｃ１－６アルキル基、Ｃ３－６アルケニル基、Ｃ３－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員へテロアリール基または４～１０員非芳香族ヘテロ環式基を意味する。ただし、Ｒ１１ａおよびＲ１１ｂは、下記置換基群ａまたは下記置換基群ｂから選ばれる置換基を有していてもよい。）を意味する。
　ただし、Ｒ１は、下記置換基群ａまたは下記置換基群ｂから選ばれる置換基を有していてもよい。
　Ｒ１の好適な例としては、式
Figure JPOXMLDOC01-appb-C000009
 （式中、ａは、１ないし４の整数を意味する。）で表される基、式
Figure JPOXMLDOC01-appb-C000010
 （式中、ｂは、１ないし３の整数を意味する。Ｚは、酸素原子、硫黄原子、カルボニル基、スルホニル基または式－ＮＲＺ－（式中、ＲＺは、水素原子またはＣ１－６アルキル基を意味する。）で表される基を意味する。）で表される基（ただし、上記式（ＩＩ）および式（ＩＩＩ）で表される基は、下記置換基群ａまたは下記置換基群ｂから選ばれる置換基を有していてもよい。）または式－ＮＲ１１ｃＲ１１ｄ（式中、Ｒ１１ｃは、水素原子またはＣ１－６アルキル基を意味する。Ｒ１１ｄは、Ｃ１－６アルキル基または式
Figure JPOXMLDOC01-appb-C000011
 （式中、ｃは、１ないし３の整数を意味する。Ｚ１は、酸素原子、硫黄原子、カルボニル基、スルホニル基または式－ＮＲＺ１－（式中、ＲＺ１は、水素原子またはＣ１－６アルキル基を意味する。）で表される基を意味する。）で表される基を意味する。ただし、Ｒ１１ｄは、下記置換基群ａまたは下記置換基群ｂから選ばれる置換基を有していてもよい。）で表される基があげられる。
　Ｒ１のより好適な例としては、アゼチジン－１－イル基、ピロリジン－１－イル基、ピペリジン－１－イル基、アゼパン－１－イル基、ピペラジン－１－イル基、ジアゼパン－１－イル基、モルホリン－４－イル基、チオモルホリン－４－イル基、１，１－ジオキソチオモルホリン－４－イル基または式－ＮＲ１１ｅＲ１１ｆ（式中、Ｒ１１ｅは、水素原子またはＣ１－６アルキル基を意味する。Ｒ１１ｆは、Ｃ１－６アルキル基、ピロリジン－３－イル基、ピペリジン－３－イル基、ピペリジン－４－イル基またはテトラヒドロピラン－４－イル基を意味する。ただし、Ｒ１１ｆは、下記置換基群ｄから選ばれる置換基を有していてもよい。）で表される基（ただし、上記各基は、下記置換基群ｄから選ばれる置換基を有していてもよい。）があげられる。
　Ｒ１のさらに好適な例としては、アゼチジン－１－イル基、ピロリジン－１－イル基、ピペリジン－１－イル基、ピペラジン－１－イル基、ジアゼパン－１－イル基、モルホリン－４－イル基（ただし、上記各基は、下記置換基群ｅから選ばれる置換基を有していてもよい。）または式－ＮＲ１１ｇＲ１１ｈ（式中、Ｒ１１ｇは、水素原子またはメチル基を意味する。Ｒ１１ｈは、ｎ－プロピル基、ｎ－ブチル基、ピロリジン－３－イル基、ピペリジン－３－イル基、ピペリジン－４－イル基またはテトラヒドロピラン－４－イル基を意味する。ただし、Ｒ１１ｈは、下記置換基群ｆから選ばれる置換基を有していてもよい。）で表される基があげられる。
　Ｒ１の特に好適な例としては、アゼチジン－１－イル基、ピロリジン－１－イル基、ピペリジン－１－イル基もしくはピペラジン－１－イル基（ただし、アゼチジン－１－イル基は、下記置換基群ｇから選ばれる置換基を有していてもよく、ピロリジン－１－イル基、ピペリジン－１－イル基およびピペラジン－１－イル基は、下記置換基群ｇから選ばれる置換基を有する。）または式－Ｎ（ＣＨ３）Ｒ１１ｉ（式中、Ｒ１１ｉは、ｎ－プロピル基、ｎ－ブチル基、ピロリジン－３－イル基またはピペリジン－４－イル基を意味する。ただし、Ｒ１１ｉは、下記置換基群ｈから選ばれる置換基を有する。）で表される基があげられる。
　Ｒ１の最も好適な例としては、アゼチジン－１－イル基、ピロリジン－１－イル基、ピペリジン－１－イル基またはピペラジン－１－イル基（ただし、アゼチジン－１－イル基は、下記置換基群ｇ－１から選ばれる置換基を有していてもよく、ピロリジン－１－イル基、ピペリジン－１－イル基およびピペラジン－１－イル基は、下記置換基群ｇ－１から選ばれる置換基を有する。）、ジメチルアミノ基を有するアゼチジン－１－イル基、ジメチルアミノ基を有するピロリジン－１－イル基、ジメチルアミノ基を有するピペリジン－１－イル基、式－Ｎ（ＣＨ３）Ｒ１１ｊ（式中、Ｒ１１ｊは、１－メチルピペリジン－４－イル基または１－エチルピペリジン－４－イル基を意味する。）で表される基、下記置換基群ｇ－２から選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｇ－２から選ばれる置換基を有するピロリジン－１－イル基、下記置換基群ｇ－２から選ばれる置換基を有するピペリジン－１－イル基または式－Ｎ（ＣＨ３）Ｒ１１ｋ（式中、Ｒ１１ｋは、１－メチルピペリジン－４－イル基、１－エチルピペリジン－４－イル基、３－（ジメチルアミノ）プロピル基または１－［２－（ジメチルアミノ）エチル］ピペリジン－４－イル基を意味する。）で表される基があげられる。
　また、Ｒ１の最も好適な例としては、［２－（ジメチルアミノ）エチル］ピペラジン－１－イル基、４－ピロリジン－１－イルピペリジン－１－イル基、４－［（ジメチルアミノ）メチル］ピペリジン－１－イル基、４－アゼチジン－１－イルピペリジン－１－イル基、４－［３－（ジメチルアミノ）アゼチジン－１－イル］ピペリジン－１－イル基、４－（４－メチルピペラジン－１－イル）ピペリジン－１－イル基、４－（１－メチルピペリジン－４－イル）ピペラジン－１－イル基、４－（１－メチルアゼチジン－３－イル）ピペラジン－１－イル基、４－（ジメチルアミノ）ピペリジン－１－イル基、４－（アゼチジン－１－イルメチル）ピペリジン－１－イル基、４－（ピロリジン－１－イルメチル）ピペリジン－１－イル基、（３Ｓ）－３－（ジメチルアミノ）ピロリジン－１－イル基、（３Ｒ）－３－（ジメチルアミノ）ピロリジン－１－イル基、アゼチジン－１－イル基、ピロリジン－１－イル基、モルホリン－４－イル基、４－メチルピペラジン－１－イル基、３－ヒドロキシアゼチジン－１－イル基、１，３’－ビアゼチジン－１’－イル基、３－（ヒドロキシメチル）アゼチジン－１－イル基、３－（ジメチルアミノ）アゼチジン－１－イル基、３－［（ジメチルアミノ）メチル］アゼチジン－１－イル基、４－ヒドロキシピペリジン－１－イル基、４－（ヒドロキシメチル）ピペリジン－１－イル基、（３Ｒ）－３－ヒドロキシピロリジン－１－イル基、（３Ｓ）－３－ヒドロキシピロリジン－１－イル基、３－（アゼチジン－１－イルメチル）アゼチジン－１－イル基、３－（２－ジメチルアミノアセトキシ）アゼチジン－１－イル基、メチル（１－メチルピペリジン－４－イル）アミノ基、（１－エチルピペリジン－４－イル）（メチル）アミノ基、［３－（ジメチルアミノ）プロピル］（メチル）アミノ基または｛１－［２－（ジメチルアミノ）エチル］ピペリジン－４－イル｝（メチル）アミノ基があげられる。 [Significance of R 1 ]
R 1 is a 3- to 10-membered non-aromatic heterocyclic group (provided that a nitrogen atom is necessarily contained in the atoms constituting the ring and a bond is drawn from the nitrogen atom) or a formula — NR 11a R 11b (wherein R 11a and R 11b are the same or different and each represents a hydrogen atom, a C 1-6 alkyl group, a C 3-6 alkenyl group, a C 3-6 alkynyl group, a C 3-10 cycloalkyl group) Group, C 6-10 aryl group, 5- to 10-membered heteroaryl group or 4- to 10-membered non-aromatic heterocyclic group, provided that R 11a and R 11b are the following substituent group a or the following substituents Which may have a substituent selected from group b).
However, R 1 may have a substituent selected from the following substituent group a or the following substituent group b.
Suitable examples of R 1 include the formula
Figure JPOXMLDOC01-appb-C000009
 (Wherein a represents an integer of 1 to 4), a group represented by the formula
Figure JPOXMLDOC01-appb-C000010
 (Wherein b represents an integer of 1 to 3. Z represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, or a formula —NR Z — (wherein R Z represents a hydrogen atom or C 1- 6 means an alkyl group.) (Wherein the groups represented by the above formulas (II) and (III) are the following substituent group a or Which may have a substituent selected from the substituent group b) or a formula —NR 11c R 11d (wherein R 11c represents a hydrogen atom or a C 1-6 alkyl group. R 11d represents C 1-6 alkyl group or formula
Figure JPOXMLDOC01-appb-C000011
 (Wherein c is an integer of 1 to 3. Z 1 is an oxygen atom, sulfur atom, carbonyl group, sulfonyl group or formula —NR Z1 — (wherein R Z1 is a hydrogen atom or C 1 Means a -6 alkyl group.) Means a group represented by). However, R 11d may have a substituent selected from the following substituent group a or the following substituent group b. ).
More preferred examples of R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group, azepan-1-yl group, piperazin-1-yl group, diazepan-1-yl A group, morpholin-4-yl group, thiomorpholin-4-yl group, 1,1-dioxothiomorpholin-4-yl group or a formula —NR 11e R 11f (wherein R 11e is a hydrogen atom or C 1 .R 11f meaning -6 alkyl group means a C 1-6 alkyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group However, R 11f may have a substituent selected from the following substituent group d. (However, each of the above groups is a substituent selected from the following substituent group d.) Have Good).
More preferred examples of R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group, piperazin-1-yl group, diazepan-1-yl group, morpholin-4-yl A group (wherein each group may have a substituent selected from the following substituent group e) or a formula —NR 11g R 11h (wherein R 11g represents a hydrogen atom or a methyl group) R 11h represents an n-propyl group, n-butyl group, pyrrolidin-3-yl group, piperidin-3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group, provided that R 11h may have a substituent selected from the following substituent group f)).
Particularly preferred examples of R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group or piperazin-1-yl group (provided that azetidin-1-yl group has the following substituents) The pyrrolidin-1-yl group, the piperidin-1-yl group and the piperazin-1-yl group may have a substituent selected from the following substituent group g. ) Or the formula —N (CH 3 ) R 11i (wherein R 11i represents an n-propyl group, an n-butyl group, a pyrrolidin-3-yl group, or a piperidin-4-yl group, provided that R 11i has a substituent selected from the following substituent group h)).
Most preferred examples of R 1 include azetidin-1-yl group, pyrrolidin-1-yl group, piperidin-1-yl group or piperazin-1-yl group (provided that the azetidin-1-yl group is substituted by The pyrrolidin-1-yl group, piperidin-1-yl group and piperazin-1-yl group may be selected from the following substituent group g-1 Azetidin-1-yl group having a dimethylamino group, pyrrolidin-1-yl group having a dimethylamino group, piperidin-1-yl group having a dimethylamino group, formula —N (CH 3 ) R 11j (wherein, R 11j is meant 1-methylpiperidin-4-yl group or 1-ethyl-piperidin-4-yl group.), a group represented by selected from the following substituent group g-2 An azetidin-1-yl group which may have a substituent, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g-2, and a substituent selected from the following substituent group g-2 A piperidin-1-yl group or a formula —N (CH 3 ) R 11k (wherein R 11k is a 1-methylpiperidin-4-yl group, a 1-ethylpiperidin-4-yl group, 3- (dimethylamino); A propyl group or a 1- [2- (dimethylamino) ethyl] piperidin-4-yl group)).
The most preferred examples of R 1 include [2- (dimethylamino) ethyl] piperazin-1-yl group, 4-pyrrolidin-1-ylpiperidin-1-yl group, 4-[(dimethylamino) methyl ] Piperidin-1-yl group, 4-azetidin-1-yl piperidin-1-yl group, 4- [3- (dimethylamino) azetidin-1-yl] piperidin-1-yl group, 4- (4-methyl Piperazin-1-yl) piperidin-1-yl group, 4- (1-methylpiperidin-4-yl) piperazin-1-yl group, 4- (1-methylazetidin-3-yl) piperazin-1-yl A 4- (dimethylamino) piperidin-1-yl group, a 4- (azetidin-1-ylmethyl) piperidin-1-yl group, a 4- (pyrrolidin-1-ylmethyl) piperidin-1-yl group, 3S) -3- (dimethylamino) pyrrolidin-1-yl group, (3R) -3- (dimethylamino) pyrrolidin-1-yl group, azetidin-1-yl group, pyrrolidin-1-yl group, morpholine-4 -Yl group, 4-methylpiperazin-1-yl group, 3-hydroxyazetidin-1-yl group, 1,3'-biazetidin-1'-yl group, 3- (hydroxymethyl) azetidin-1-yl group 3- (dimethylamino) azetidin-1-yl group, 3-[(dimethylamino) methyl] azetidin-1-yl group, 4-hydroxypiperidin-1-yl group, 4- (hydroxymethyl) piperidin-1- Yl group, (3R) -3-hydroxypyrrolidin-1-yl group, (3S) -3-hydroxypyrrolidin-1-yl group, 3- (azetidin-1-ylmethyl) azetidine 1-yl group, 3- (2-dimethylaminoacetoxy) azetidin-1-yl group, methyl (1-methylpiperidin-4-yl) amino group, (1-ethylpiperidin-4-yl) (methyl) amino group [3- (dimethylamino) propyl] (methyl) amino group or {1- [2- (dimethylamino) ethyl] piperidin-4-yl} (methyl) amino group.
［置換基群ａの意義］
　置換基群ａは、ハロゲン原子、水酸基、メルカプト基、ニトロ基、シアノ基およびオキソ基からなる群を意味する。 [Significance of Substituent Group a]
The substituent group a means a group consisting of a halogen atom, a hydroxyl group, a mercapto group, a nitro group, a cyano group, and an oxo group.
［置換基群ｂの意義］
　置換基群ｂは、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基、３～１０員非芳香族ヘテロ環式基、Ｃ１－６アルコキシ基、Ｃ３－６アルケニルオキシ基、Ｃ３－６アルキニルオキシ基、Ｃ３－１０シクロアルコキシ基、Ｃ６－１０アリールオキシ基、５～１０員ヘテロアリールオキシ基、４～１０員非芳香族ヘテロ環オキシ基、Ｃ１－６アルキルチオ基、Ｃ３－６アルケニルチオ基、Ｃ３－６アルキニルチオ基、Ｃ３－１０シクロアルキルチオ基、Ｃ６－１０アリールチオ基、５～１０員ヘテロアリールチオ基、４～１０員非芳香族ヘテロ環チオ基および式－Ｔ１－Ｔ２－Ｔ３　(式中、Ｔ１は、単結合またはＣ１－６アルキレン基を意味する。
　Ｔ２は、カルボニル基、スルフィニル基、スルホニル基、式－Ｃ（＝Ｏ）－Ｏ－で表される基、式－Ｏ－Ｃ（＝Ｏ）－で表される基、式－ＳＯ２－Ｏ－で表される基、式－Ｏ－ＳＯ２－で表される基、式－ＮＲＴ１－で表される基、式－Ｃ（＝Ｏ）－ＮＲＴ１－で表される基、式－ＮＲＴ１－Ｃ（＝Ｏ）－で表される基、式－ＳＯ２－ＮＲＴ１－で表される基または式－ＮＲＴ１－ＳＯ２－で表される基を意味する。
　Ｔ３は、水素原子、Ｃ１－６アルキル基、Ｃ３－６アルケニル基、Ｃ３－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基または４～１０員非芳香族ヘテロ環式基を意味する。
　ＲＴ１は、水素原子またはＣ１－６アルキル基を意味する。）で表される基からなる群を意味する。
　ただし、置換基群ｂに記載の各基は、下記置換基群ｃから選ばれる置換基を有していてもよい。 [Significance of Substituent Group b]
Substituent group b includes a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-10 cycloalkyl group, a C 6-10 aryl group, a 5-10 membered heteroaryl group, 3- to 10-membered non-aromatic heterocyclic group, C 1-6 alkoxy group, C 3-6 alkenyloxy group, C 3-6 alkynyloxy group, C 3-10 cycloalkoxy group, C 6-10 aryloxy group 5- to 10-membered heteroaryloxy group, 4- to 10-membered non-aromatic heterocyclic oxy group, C 1-6 alkylthio group, C 3-6 alkenylthio group, C 3-6 alkynylthio group, C 3-10 cyclo An alkylthio group, a C 6-10 arylthio group, a 5- to 10-membered heteroarylthio group, a 4- to 10-membered non-aromatic heterocyclic thio group and a formula —T 1 -T 2 -T 3 (wherein T 1 is a single bond or C 1- It means an alkylene group.
T 2 is a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula —C (═O) —O—, a group represented by the formula —O—C (═O) —, or a formula —SO 2 —. A group represented by the formula O—, a group represented by the formula —O—SO 2 —, a group represented by the formula —NR T1 —, a group represented by the formula —C (═O) —NR T1 —, a formula It means a group represented by —NR T1 —C (═O) —, a group represented by the formula —SO 2 —NR T1 — or a group represented by the formula —NR T1 —SO 2 —.
T 3 is a hydrogen atom, a C 1-6 alkyl group, a C 3-6 alkenyl group, a C 3-6 alkynyl group, a C 3-10 cycloalkyl group, a C 6-10 aryl group, or a 5-10 membered heteroaryl group Or a 4- to 10-membered non-aromatic heterocyclic group.
R T1 means a hydrogen atom or a C 1-6 alkyl group. ) Represents a group consisting of groups represented by
However, each group described in the substituent group b may have a substituent selected from the following substituent group c.
［置換基群ｃの意義］
　置換基群ｃは、ハロゲン原子、水酸基、メルカプト基、ニトロ基、シアノ基、オキソ基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基、３～１０員非芳香族ヘテロ環式基、Ｃ１－６アルコキシ基、Ｃ１－６アルキルチオ基、モノ－Ｃ１－６アルキルアミノ基およびジ－Ｃ１－６アルキルアミノ基からなる群を意味する。 [Significance of Substituent Group c]
Substituent group c includes halogen atom, hydroxyl group, mercapto group, nitro group, cyano group, oxo group, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-10 cycloalkyl Group, C 6-10 aryl group, 5-10 membered heteroaryl group, 3-10 membered non-aromatic heterocyclic group, C 1-6 alkoxy group, C 1-6 alkylthio group, mono-C 1-6 alkyl It means a group consisting of an amino group and a di-C 1-6 alkylamino group.
［置換基群ｄの意義］
　置換基群ｄは、ハロゲン原子、水酸基、メルカプト基、シアノ基、ホルミル基、オキソ基、Ｃ１－６アルキル基、Ｃ３－１０シクロアルキル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基、ジ－Ｃ１－６アルキルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジアゼパニル基および式－Ｔ４－Ｔ５　(式中、Ｔ４は、カルボニル基またはスルホニル基を意味する。
　Ｔ５は、Ｃ１－６アルキル基、Ｃ３－１０シクロアルキル基、アゼチジニル基、ピロリジニル基、ピペリジニル基、水酸基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基またはジ－Ｃ１－６アルキルアミノ基を意味する。）で表される基からなる群を意味する。
　ただし、置換基群ｄに記載の各基は、水酸基、Ｃ１－６アルキル基、ジ－Ｃ１－６アルキルアミノ基、アゼチジニル基またはピロリジニル基を有していてもよい。 [Significance of Substituent Group d]
Substituent group d includes a halogen atom, a hydroxyl group, a mercapto group, a cyano group, a formyl group, an oxo group, a C 1-6 alkyl group, a C 3-10 cycloalkyl group, a C 1-6 alkoxy group, an amino group, a mono- A C 1-6 alkylamino group, a di-C 1-6 alkylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a diazepanyl group, and a formula —T 4 -T 5 (wherein T 4 is a carbonyl group) Or a sulfonyl group is meant.
T 5 is a C 1-6 alkyl group, a C 3-10 cycloalkyl group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a hydroxyl group, a C 1-6 alkoxy group, an amino group, a mono-C 1-6 alkylamino group or Means a di-C 1-6 alkylamino group; ) Represents a group consisting of groups represented by
However, each group described in the substituent group d may have a hydroxyl group, a C 1-6 alkyl group, a di-C 1-6 alkylamino group, an azetidinyl group, or a pyrrolidinyl group.
［置換基群ｅの意義］
　置換基群ｅは、メチル基、エチル基、ジメチルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基およびピペラジニル基を意味する。
　ただし、置換基群ｅに記載の各基は、水酸基、メチル基、ジメチルアミノ基、アゼチジニル基、ピロリジニル基またはピペリジニル基を有していてもよい。 [Significance of Substituent Group e]
The substituent group e means a methyl group, an ethyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, and a piperazinyl group.
However, each group described in the substituent group e may have a hydroxyl group, a methyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, or a piperidinyl group.
［置換基群ｆの意義］
　置換基群ｆは、メチル基、エチル基、ｎ－プロピル基、アセチル基、ジメチルアミノ基、ジエチルアミノ基、アゼチジニル基、ピロリジニル基およびピペラジニル基を意味する。
　ただし、置換基群ｆに記載の各基は、メチル基またはジメチルアミノ基を有していてもよい。 [Significance of Substituent Group f]
The substituent group f means a methyl group, an ethyl group, an n-propyl group, an acetyl group, a dimethylamino group, a diethylamino group, an azetidinyl group, a pyrrolidinyl group, and a piperazinyl group.
However, each group described in the substituent group f may have a methyl group or a dimethylamino group.
［置換基群ｇの意義］
　置換基群ｇは、ジメチルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジメチルアミノメチル基、ジメチルアミノエチル基、アゼチジン－１－イルメチル基、ピロリジン－１－イルメチル基およびピペリジン－１－イルメチル基を意味する。
　ただし、置換基群ｇに記載の各基は、メチル基またはジメチルアミノ基を有していてもよい。 [Significance of Substituent Group g]
Substituent group g includes dimethylamino group, azetidinyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group, dimethylaminomethyl group, dimethylaminoethyl group, azetidin-1-ylmethyl group, pyrrolidin-1-ylmethyl group and piperidin-1- It means an ylmethyl group.
However, each group described in the substituent group g may have a methyl group or a dimethylamino group.
[置換基群ｇ－１の意義]
　置換基群ｇ－１は、アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジメチルアミノメチル基、ジメチルアミノエチル基、アゼチジン－１－イルメチル基、ピロリジン－１－イルメチル基およびピペリジン－１－イルメチル基を意味する。
　ただし、置換基群ｇ－１に記載の各基は、メチル基またはジメチルアミノ基を有していてもよい。 [Significance of Substituent Group g-1]
Substituent group g-1 includes azetidinyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group, dimethylaminomethyl group, dimethylaminoethyl group, azetidin-1-ylmethyl group, pyrrolidin-1-ylmethyl group and piperidin-1-ylmethyl group Means.
However, each group described in the substituent group g-1 may have a methyl group or a dimethylamino group.
［置換基群ｇ－２の意義］
　置換基群ｇ－２は、水酸基、メトキシ基、ヒドロキシメチル基およびジメチルアミノアセトキシ基を意味する。 [Significance of Substituent Group g-2]
Substituent group g-2 means a hydroxyl group, a methoxy group, a hydroxymethyl group, and a dimethylaminoacetoxy group.
［置換基群ｈの意義］
　置換基群ｈは、ジメチルアミノ基、ジエチルアミノ基、ジメチルアミノエチル基、ジメチルアミノプロピル基および１－メチルアゼチジン－３－イル基を意味する。 [Significance of Substituent Group h]
The substituent group h means a dimethylamino group, a diethylamino group, a dimethylaminoethyl group, a dimethylaminopropyl group and a 1-methylazetidin-3-yl group.
［Ｒ２およびＲ３の意義］
　Ｒ２およびＲ３は、水素原子を意味する。 [Significance of R 2 and R 3 ]
R 2 and R 3 represent a hydrogen atom.
［Ｒ４、Ｒ５、Ｒ６およびＲ７の意義］
　Ｒ４、Ｒ５、Ｒ６およびＲ７は、同一または異なって、水素原子、ハロゲン原子、水酸基、シアノ基、トリフルオロメチル基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基、ジ－Ｃ１－６アルキルアミノ基、式－ＣＯ－Ｒ１２（式中、Ｒ１２は、水素原子、水酸基、Ｃ１－６アルキル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基またはジ－Ｃ１－６アルキルアミノ基を意味する。）で表される基を意味する。
　Ｒ４、Ｒ５、Ｒ６およびＲ７の好適な例としては、水素原子、ハロゲン原子、Ｃ１－６アルキル基、Ｃ１－６アルコキシ基またはトリフルオロメチル基があげられる。
　Ｒ４、Ｒ５、Ｒ６およびＲ７のより好適な例としては、水素原子、ハロゲン原子またはＣ１－６アルキル基があげられる。
　Ｒ４、Ｒ５、Ｒ６およびＲ７のさらに好適な例としては、水素原子、フッ素原子、塩素原子またはメチル基があげられる。
　Ｒ４、Ｒ５、Ｒ６およびＲ７は、１）全て水素原子である場合、２）全て水素原子以外の置換基である場合、３）水素原子または水素原子以外の置換基である場合のいずれでもよいが、好適にはＲ４、Ｒ５、Ｒ６およびＲ７のうち、２ないし４個が水素原子である。
　なお、式
Figure JPOXMLDOC01-appb-C000012
 で表される基の好適な例としては、式
Figure JPOXMLDOC01-appb-C000013
 で表される基または式
Figure JPOXMLDOC01-appb-C000014
 で表される基があげられる。 [Significance of R 4 , R 5 , R 6 and R 7 ]
R 4 , R 5 , R 6 and R 7 are the same or different and are a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a trifluoromethyl group, a C 1-6 alkyl group, a C 2-6 alkenyl group, C 2 -6 alkynyl group, C 1-6 alkoxy group, amino group, mono-C 1-6 alkylamino group, di-C 1-6 alkylamino group, formula —CO—R 12 wherein R 12 is hydrogen An atom, a hydroxyl group, a C 1-6 alkyl group, a C 1-6 alkoxy group, an amino group, a mono-C 1-6 alkylamino group or a di-C 1-6 alkylamino group). Means.
Preferable examples of R 4 , R 5 , R 6 and R 7 include a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group or a trifluoromethyl group.
More preferred examples of R 4 , R 5 , R 6 and R 7 include a hydrogen atom, a halogen atom or a C 1-6 alkyl group.
More preferred examples of R 4 , R 5 , R 6 and R 7 include a hydrogen atom, a fluorine atom, a chlorine atom or a methyl group.
R 4 , R 5 , R 6 and R 7 are 1) when all are hydrogen atoms, 2) when all are substituents other than hydrogen atoms, 3) when they are substituents other than hydrogen atoms or hydrogen atoms Any of them may be used, but preferably 2 to 4 of R 4 , R 5 , R 6 and R 7 are hydrogen atoms.
The formula
Figure JPOXMLDOC01-appb-C000012
 As preferable examples of the group represented by the formula:
Figure JPOXMLDOC01-appb-C000013
 A group or formula represented by
Figure JPOXMLDOC01-appb-C000014
 And a group represented by
［Ｒ８の意義］
　Ｒ８は、水素原子またはＣ１－６アルキル基を意味する。
　Ｒ８の好適な例としては、水素原子があげられる。 [The significance of R 8]
R 8 represents a hydrogen atom or a C 1-6 alkyl group.
A preferred example of R 8 is a hydrogen atom.
［Ｒ９の意義］
　Ｒ９は、３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）または式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、上記定義と同意義を意味する）で表される基で表される基を意味する。
　ただし、Ｒ９は、上記置換基群ａまたは上記置換基群ｂから選ばれる置換基を有していてもよい。
　Ｒ９の好適な例としては、モノ－Ｃ１－６アルキルアミノ基、モノ－Ｃ３－１０シクロアルキルアミノ基、モノ－Ｃ６－１０アリールアミノ基、モノ－５～１０員へテロアリールアミノ基またはモノ－４～１０員非芳香族ヘテロ環アミノ基があげられる（ただし、Ｒ９は、上記置換基群ａまたは上記置換基群ｂから選ばれる置換基を有していてもよい。）。
　Ｒ９のより好適な例としては、モノ－Ｃ３－１０シクロアルキルアミノ基またはモノ－Ｃ６－１０アリールアミノ基があげられる（ただし、Ｒ９は、上記置換基群ａまたは上記置換基群ｂから選ばれる置換基を有していてもよい。）。
　Ｒ９のさらに好適な例としては、モノ－Ｃ３－１０シクロアルキルアミノ基またはモノ－Ｃ６－１０アリールアミノ基があげられる（ただし、Ｒ９は、下記置換基群ｉから選ばれる置換基を有していてもよい。）。
［置換基群ｉ］
ハロゲン原子、トリフルオロメチル基、シアノ基、Ｃ１－６アルキル基およびＣ１－６アルコキシ基。
　Ｒ９の特に好適な例としては、シクロペンチルアミノ基、シクロヘキシルアミノ基、シクロヘプチルアミノ基、フェニルアミノ基があげられる（ただし、Ｒ９は、上記置換基群ｉから選ばれる置換基を有していてもよい。）。
　Ｒ９の最も好適な例としては、上記置換基群ｉから選ばれる置換基を有していてもよいフェニルアミノ基があげられる。 [Significance of R 9 ]
R 9 represents a 3- to 10-membered non-aromatic heterocyclic group (provided that a nitrogen atom is necessarily contained in the atoms constituting the ring and a bond is drawn from the nitrogen atom) or a formula — A group represented by a group represented by NR 11a R 11b (wherein R 11a and R 11b have the same meanings as defined above).
However, R 9 may have a substituent selected from the substituent group a or the substituent group b.
Preferable examples of R 9 include mono-C 1-6 alkylamino group, mono-C 3-10 cycloalkylamino group, mono-C 6-10 arylamino group, mono-5-10 membered heteroarylamino Group or a mono-4 to 10-membered non-aromatic heterocyclic amino group (provided that R 9 may have a substituent selected from the substituent group a or the substituent group b). .
As a more preferable example of R 9 is mono- -C 3-10 cycloalkylamino or mono -C 6-10 arylamino group (wherein, R 9 is the above-mentioned substituent group a or the above-mentioned substituent group It may have a substituent selected from b).
More preferable examples of R 9 include a mono-C 3-10 cycloalkylamino group or a mono-C 6-10 arylamino group (wherein R 9 is a substituent selected from the following substituent group i) May be included.)
[Substituent group i]
A halogen atom, a trifluoromethyl group, a cyano group, a C 1-6 alkyl group and a C 1-6 alkoxy group;
Particularly preferred examples of R 9 include a cyclopentylamino group, a cyclohexylamino group, a cycloheptylamino group, and a phenylamino group (provided that R 9 has a substituent selected from the above substituent group i). May be.)
A most preferred example of R 9 is a phenylamino group which may have a substituent selected from the above substituent group i.
［ｎの意義］
　ｎは、１ないし２の整数を意味する。
　ｎの好適な例としては、１である。 [Significance of n]
n means an integer of 1 to 2.
A preferred example of n is 1.
［Ｘの意義］
　Ｘは、式－Ｃ（Ｒ１０）＝（式中、Ｒ１０は、水素原子、ハロゲン原子、シアノ基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、式－ＣＯ－Ｒ１２（式中、Ｒ１２は、上記定義と同意義を意味する。）で表される基を意味する。）で表される基または窒素原子を意味する。
　Ｘの好適な例としては、式－Ｃ（Ｒ１０ａ）＝（式中、Ｒ１０ａは、水素原子、ハロゲン原子またはシアノ基を意味する。）で表される基または窒素原子があげられる。
　Ｘのより好適な例としては、式－ＣＨ＝で表される基または窒素原子があげられる。 [Significance of X]
X represents the formula —C (R 10 ) = (wherein R 10 represents a hydrogen atom, a halogen atom, a cyano group, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a formula (wherein, R 12 means the the same meanings as defined.) -CO-R 12 means a group represented by.) refers to a group or a nitrogen atom represented by.
Preferable examples of X include a group represented by the formula —C (R 10a ) = (wherein R 10a represents a hydrogen atom, a halogen atom or a cyano group) or a nitrogen atom.
More preferable examples of X include a group represented by the formula —CH═ or a nitrogen atom.
　一般式（Ｉ）における好ましい化合物として、当該化合物における上記Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５、Ｒ６、Ｒ７、Ｒ８、Ｒ９、Ｘおよびｎの各態様を選択し、それらを任意に組み合わせた化合物をあげることができる。 As a preferable compound in the general formula (I), each aspect of the R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X and n in the compound is selected. And compounds in which they are arbitrarily combined.
　一般式（Ｉ）における化合物の具体例としては、以下に例示する化合物をあげることができる。
（１）Ｎ－（４－｛［２－（｛［（１－ｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２）Ｎ－（４－｛［２－（｛［（１－ｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（４－ｍｅｔｈｙｌ－１，４－ｄｉａｚｅｐａｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４）Ｎ－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（５）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（６）Ｎ－［４－（｛２－［（｛４－［２－（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｅｔｈｙｌ］－１，４－ｄｉａｚｅｐａｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（７）Ｎ－（４－｛［２－（｛［３－（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（８）Ｎ－（４－｛［２－（｛［３－（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（９）Ｎ－（４－｛［２－（｛［３－（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１０）Ｎ－［２－ｆｌｕｏｒｏ－４－（｛２－［（｛ｍｅｔｈｙｌ［１－（１－ｍｅｔｈｙｌａｚｅｔｉｄｉｎ－３－ｙｌ）ｐｉｐｅｒｉｄｉｎ－４－ｙｌ］ａｍｉｎｏ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１１）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［４－（１－ｍｅｔｈｙｌａｚｅｔｉｄｉｎ－３－ｙｌ）ｐｉｐｅｒａｚｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１２）Ｎ－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－｛［２－（｛［４－（１－ｍｅｔｈｙｌａｚｅｔｉｄｉｎ－３－ｙｌ）ｐｉｐｅｒａｚｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１３）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１４）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（４－ｈｙｄｒｏｘｙ－１，４’－ｂｉｐｉｐｅｒｉｄｉｎ－１’－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１５）Ｎ－（４－｛［２－（｛［｛１－［３－（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｒｏｐｙｌ］ｐｉｐｅｒｉｄｉｎ－４－ｙｌ｝（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１６）Ｎ－（４－｛［２－（｛［（３－ａｚｅｔｉｄｉｎ－１－ｙｌｐｒｏｐｙｌ）（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１７）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（３－ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｐｒｏｐｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１８）Ｎ－（４－｛［２－（｛［［３－（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｒｏｐｙｌ］（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１９）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（４－ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｂｕｔｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２０）Ｎ－［２－ｆｌｕｏｒｏ－４－（｛２－［（ｍｏｒｐｈｏｌｉｎ－４－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２１）Ｎ－［４－（｛２－［（ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２２）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（３－ｍｏｒｐｈｏｌｉｎ－４－ｙｌｐｒｏｐｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２３）Ｎ－［２－ｆｌｕｏｒｏ－４－（｛２－［（｛ｍｅｔｈｙｌ［３－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｒｏｐｙｌ］ａｍｉｎｏ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２４）Ｎ－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－［２－ｆｌｕｏｒｏ－４－（｛２－［（ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２５）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－２－ｔｈｉｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２６）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－１，３－ｔｈｉａｚｏｌ－２－ｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２７）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（５－ｍｅｔｈｙｌｉｓｏｘａｚｏｌ－３－ｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２８）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（３－ｍｅｔｈｙｌｉｓｏｘａｚｏｌ－５－ｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２９）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（４－ｈｙｄｒｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３０）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（４－ｍｅｔｈｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３１）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３２）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｍｅｔｈｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３３）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［（２－ｍｅｔｈｏｘｙｅｔｈｙｌ）（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３４）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［４－（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３５）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（ｔｅｔｒａｈｙｄｒｏ－２Ｈ－ｐｙｒａｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３６）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－３－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３７）Ｎ－［４－（｛２－［（｛３－［（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ｐｉｐｅｒｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３８）Ｎ－［４－（｛２－［（｛３－［（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３９）Ｎ－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｙｒｒｏｌｉｄｉｎ－３－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４０）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４１）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｍｅｔｈｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４２）Ｎ－｛４－［（２－｛［（３，４－ｄｉｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］－２－ｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４３）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙ－４－ｍｅｔｈｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４４）Ｎ－｛４－［（２－｛［（３，４－ｄｉｍｅｔｈｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］－２－ｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４５）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４６）Ｎ－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（３－ｍｅｔｈｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、および
（４７）Ｎ－（４－｛［２－（｛［３－（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ。 Specific examples of the compound in the general formula (I) include the compounds exemplified below.
(1) N- (4-{[2-({[(1-ethylpiperidin-4-yl) (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N'- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(2) N- (4-{[2-({[(1-ethylpiperidin-4-yl) (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(3) N- {2-fluor-4--4-[(2-{[(4-methyl-1,4-diapan-1--1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(4) N- (4-fluorophenyl) -N ′-{2-fluor-4--4-[(2-{[(3-pyrrolidin-1-ylazetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} cyclopropane-1,1-dicboxamide,
(5) N- {2-fluor-4--4-[(2-{[(4-methylpiperazin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(6) N- [4-({2-[({4- [2- (dimethylamino) ethyl] -1,4-diazepan-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2 -Fluorphenyl] -N'-phenylcyclopropane-1,1-dicboxamide,
(7) N- (4-{[2-({[3- (dimethylamino) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(8) N- (4-{[2-({[3- (dimethylamino) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane -1,1-dicarboxamide,
(9) N- (4-{[2-({[3- (dimethylamino) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N'-phenylcyclopropane-1 , 1-dicarboxamide,
(10) N- [2-fluoro-4-({2-[({methyl [1- (1-methylazetidin-3-yl) piperidin-4-yl] amino} carbonyl) amino] pyridin-4-yl} oxy) phenyl] -N′-phenylcyclopropane-1,1-dicboxamide,
(11) N- (2-fluoro-4-{[2-({[4- (1-methylazetidin-3-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-phenylcyclopropane-1, 1-dicboxamide,
(12) N- (4-fluorophenyl) -N ′-(4-{[2-({[4- (1-methylazetidin-3-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl ] Oxy} phenyl) cyclopropane-1,1-dicboxamide,
(13) N- (2-fluoro-4-{[2-({[(1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4 -Fluorphenyl) cyclopropane-1,1-dicboxamide,
(14) N- {2-fluor-4--4-[(2-{[(4-hydroxy-1,4'-biperidin-1'-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl}- N′-phenylcyclopropane-1,1-dicboxamide,
(15) N- (4-{[2-({[{1- [3- (dimethylamino) propyl] piperidin-4-yl} (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy}- 2-fluorophenyl) -N′-phenylcyclopropane-1,1-dicboxamide,
(16) N- (4-{[2-({[(3-azetidin-1-ylpropyl) (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(17) N- (2-fluoro-4-{[2-({[methyl (3-pyrrolidin-1-ylpropyl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(18) N- (4-{[2-({[[(3- (dimethylamino) propyl] (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N '-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(19) N- (2-fluoro-4-{[2-({[methyl (4-pyrrolidin-1-ylbutyl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-phenylcyclopropane -1,1-dicarboxamide,
(20) N- [2-fluor-4--4-({2-[(morpholin-4-ylcarbonyl) amino] pyridin-4-yl} oxy) phenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1 -Dicarboxamide,
(21) N- [4-({2-[(azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1- dicarboxamide,
(22) N- (2-fluoro-4-{[2-({[methyl (3-morpholin-4-ylpropyl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(23) N- [2-fluoro-4-({2-[({methyl [3- (4-methylpiperazin-1-yl) propyl] amino} carbonyl) amino] pyridin-4-yl} oxy) phenyl] -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(24) N- (4-fluorophenyl) -N ′-[2-fluoro-4-({2-[(pyrrolidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) phenyl] cyclopropane-1,1 -Dicarboxamide,
(25) N- (2-fluor-4--4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-2 -Thienylcyclopropane-1,1-dicboxamide,
(26) N- (2-fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-1 , 3-thiazol-2-ylcyclopropane-1,1-dicboxamide,
(27) N- (2-fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 5-methylisoxazol-3-yl) cyclopropane-1,1-dicboxamide,
(28) N- (2-fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 3-methylisoxazol-5-yl) cyclopropane-1,1-dicboxamide,
(29) N- {2-fluoro-4-[(2-{[(4-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(30) N- {2-fluor-4--4-[(2-{[(4-methoxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N '-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(31) N- {2-fluoro-4-[(2-{[(3-hydroxyzetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(32) N- {2-fluor-4--4-[(2-{[(3-methoxyazetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N '-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(33) N- (2-fluor-4--4-{[2-({[(2-methoxyethyl) (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(34) N- (2-fluoro-4-{[2-({[4- (3-hydroxyzetidin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(35) N- (2-fluoro-4-{[2-({[methyl (tetrahydro-2H-pyran-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(36) N- (2-fluor-4--4-[[2-({[methyl (1-methylpiperidin-3-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(37) N- [4-({2-[({3-[(dimethylamino) methyl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) phenyl] -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(38) N- [4-({2-[({3-[(dimethylamino) methyl] pyrrolidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorphenyl] -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(39) N- (2-fluoro-4-{[2-({[methyl (1-methylpyrrolidin-3-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(40) N- {2-fluor-4--4-[(2-{[(3-hydroxypyrrolidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(41) N- {2-fluoro-4-[(2-{[(3-methoxypyrrolidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(42) N- {4-[(2-{[(3,4-dihydroxypyrrolidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] -2-fluorophenyl} -N '-(4-fluorophenyl ) Cyclopropane-1,1-dicboxamide,
(43) N- {2-fluor-4--4-[(2-{[(3-hydroxy-4-methoxypyrrolidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(44) N- {4-[(2-{[(3,4-dimethylpyrrolidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] -2-fluorophenyl} -N '-(4-fluorophenyl ) Cyclopropane-1,1-dicboxamide,
(45) N- {2-fluor-4--4-[(2-{[(3-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N '-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(46) N- {2-fluoro-4-[(2-{[(3-methoxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide, and (47) N- (4-{[2-({[3- (dimethylamino) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2- Fluorophenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide.
　一般式（Ｉ）における化合物のより好適な具体例としては、以下に示す化合物をあげることができる。
（１）Ｎ－［４－（｛２－［（｛４－［２－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｅｔｈｙｌ］ｐｉｐｅｒａｚｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３）Ｎ－（４－Ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－｛２－ｆｌｕｏｒｏ－４－［（２－｛［（４－ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４）Ｎ－［４－（｛２－［（｛４－［（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ｐｉｐｅｒｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（５）Ｎ－｛４－［（２－｛［（４－Ａｚｅｔｉｄｉｎ－１－ｙｌｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］－２－ｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（６）Ｎ－［４－（｛２－［（｛４－［３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｐｉｐｅｒｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（７）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（８）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ｐｉｐｅｒａｚｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（９）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（１－ｍｅｔｈｙｌａｚｅｔｉｄｉｎ－３－ｙｌ）ｐｉｐｅｒａｚｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１０）Ｎ－（４－｛［２－（｛［４－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１１）Ｎ－（４－｛［２－（｛［４－（Ａｚｅｔｉｄｉｎ－１－ｙｌｍｅｔｈｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１２）Ｎ－（４－Ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（２－ｆｌｕｏｒｏ－４－｛［２－（｛［４－（ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｍｅｔｈｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１３）Ｎ－（４－｛［２－（｛［（３Ｓ）－３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１４）Ｎ－（４－｛［２－（｛［（３Ｒ）－３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１５）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１６）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１７）Ｎ－［４－（｛２－［（｛４－［３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｐｉｐｅｒｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１８）Ｎ－（４－｛［２－（｛［（１－Ｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）（ｍｅｔｈｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－ｐｈｅｎｙｌｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（１９）Ｎ－［４－（｛２－［（Ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２０）Ｎ－（４－Ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－［２－ｆｌｕｏｒｏ－４－（｛２－［（ｐｙｒｒｏｌｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２１）Ｎ－｛２－Ｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２２）Ｎ－［４－（｛２－［（１，３’－Ｂｉａｚｅｔｉｄｉｎ－１’－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２３）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２４）Ｎ－（４－｛［２－（｛［３－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２－ｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２５）Ｎ－［４－（｛２－［（｛３－［（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ａｚｅｔｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２６）Ｎ－｛２－Ｆｌｕｏｒｏ－４－［（２－｛［（４－ｈｙｄｒｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２７）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２８）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｒ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（２９）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｓ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３０）Ｎ－［４－（｛２－［（Ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３１）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３２）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３３）Ｎ－［２，５－Ｄｉｆｌｕｏｒｏ－４－（｛２－［（｛３－［（ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ａｚｅｔｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）ｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３４）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３５）Ｎ－｛４－［（２－｛［３－（Ａｚｅｔｉｄｉｎ－１－ｙｌｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３６）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３７）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（４－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｍｉｄｉｎ－６－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３８）Ｎ－［４－（｛４－［（｛３－［（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｍｅｔｈｙｌ］ａｚｅｔｉｄｉｎ－１－ｙｌ｝ｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｍｉｄｉｎ－６－ｙｌ｝ｏｘｙ）－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（３９）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［４－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｍｉｄｉｎ－６－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４０）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［４－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｍｉｄｉｎ－６－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４１）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［４－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｍｉｄｉｎ－６－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４２）Ｎ－（４－｛［２－（｛［４－（Ｄｉｍｅｔｈｙｌａｍｉｎｏ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４３）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４４）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（４－ｈｙｄｒｏｘｙｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４５）Ｎ－｛４－［（２－｛［（４－Ａｚｅｔｉｄｉｎ－１－ｙｌｐｉｐｅｒｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｏｘｙ｝－２，５－ｄｉｆｌｕｏｒｏｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４６）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［３－（２－ｄｉｍｅｔｈｙｌａｍｉｎｏａｃｅｔｏｘｙ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、
（４７）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｓ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ、および
（４８）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［（３Ｒ）－３－ｈｙｄｒｏｘｙｐｙｒｒｏｌｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ。 Specific examples of the compound represented by the general formula (I) include the compounds shown below.
(1) N- [4-({2-[({4- [2- (Dimethylamino) ethyl] piperazin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide,
(2) N- (2-Fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(3) N- (4-Fluorophenyl) -N ′-{2-fluoro-4-[(2-{[(4-pyrrolidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} cyclopropane-1,1-dicboxamide,
(4) N- [4-({2-[({4-[(Dimethylamino) methyl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorphenyl] -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(5) N- {4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] -2-fluorophenyl} -N ′-(4 -Fluorphenyl) cyclopropane-1,1-dicboxamide,
(6) N- [4-({2-[({4- [3- (Dimethylamino) azetinin-1-yl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2- fluorphenyl] -N ′-(4-fluorphenyl) cyclopropane-1,1-dicboxamide,
(7) N- (2-Fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(8) N- (2-Fluoro-4-{[2-({[4- (1-methylpiperidin-4-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(9) N- (2-Fluoro-4-{[2-({[4- (1-methylazetidin-3-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(10) N- (4-{[2-({[4- (Dimethylamino) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(11) N- (4-{[2-({[4- (Azetidin-1-ylmethyl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(12) N- (4-Fluorophenyl) -N ′-(2-fluoro-4-{[2-({[4- (pyrrolidin-1-ylmethyl) piperidin-1-yl] carbonyl} amino) pyridin-4 -Yl] oxy} phenyl) cyclopropane-1,1-dicboxamide,
(13) N- (4-{[2-({[(3S) -3- (Dimethylamino) pyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(14) N- (4-{[2-({[(3R) -3- (Dimethylamino) pyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(15) N- (2-Fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-phenylcyclopropane -1,1-dicarboxamide,
(16) N- (2-Fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'-phenylcyclopropane-1, 1-dicboxamide,
(17) N- [4-({2-[({4- [3- (Dimethylamino) azetinin-1-yl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2- fluorphenyl] -N′-phenylcyclopropane-1,1-dicboxamide,
(18) N- (4-{[2-({[(1-Ethylpiperidin-4-yl) (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N'- phenylcyclopropane-1, 1-dicboxamide,
(19) N- [4-({2-[(Azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1- dicarboxamide,
(20) N- (4-Fluorophenyl) -N ′-[2-fluoro-4-({2-[(pyrrolidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) phenyl] cyclopropane-1,1 -Dicarboxamide,
(21) N- {2-Fluoro-4-[(2-{[(3-hydroxyazetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N '-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(22) N- [4-({2-[(1,3′-Biacetidin-1′-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(23) N- (2-Fluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4 -Fluorphenyl) cyclopropane-1,1-dicboxamide,
(24) N- (4-{[2-({[3- (Dimethylamino) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(25) N- [4-({2-[({3-[(Dimethylamino) methyl] azetinin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorphenyl] -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(26) N- {2-Fluoro-4-[(2-{[(4-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(27) N- (2-Fluoro-4-{[2-({[4- (hydroxymethyl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4 -Fluorphenyl) cyclopropane-1,1-dicboxamide,
(28) N- (2-Fluoro-4-{[2-({[(3R) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(29) N- (2-Fluoro-4-{[2-({[(3S) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(30) N- [4-({2-[(Azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2,5-difluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide,
(31) N- {2,5-Difluoro-4--4-[(2-{[(3-hydroxyzetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(32) N- (2,5-Difluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(33) N- [2,5-Difluoro-4--4-({2-[({3-[(dimethylamino) methyl] azetinin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) phenyl]- N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(34) N- (2,5-Difluoro-4--4-[[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(35) N- {4-[(2-{[3- (Azetidin-1-ylmethyl) azetinin-1-ylcarbonyl] amino} pyridin-4-yl) oxy] -2,5-difluorophenyl} -N′- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(36) N- (2,5-Difluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(37) N- {2,5-Difluoro-4--4-[(4-{[(3-hydroxyzetidin-1-yl) carbonyl] amino} pyrimidin-6-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(38) N- [4-({4-[({3-[(Dimethylamino) methyl] azetinin-1-yl} carbonyl) amino] pyrimidin-6-yl} oxy) -2,5-difluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide,
(39) N- (2,5-Difluoro-4-{[4-({[3- (hydroxymethyl) azetinin-1-yl] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N'- (4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(40) N- (2,5-Difluoro-4-{[4-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N ' -(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(41) N- (2,5-Difluoro-4--4-{[4-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(42) N- (4-{[2-({[4- (Dimethylamino) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2,5-difluorophenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicboxamide,
(43) N- {2,5-Difluoro-4--4-[(2-{[(4-methylpiperazin-1-yl) carbonyl] amino} pyridin-4-yl] oxy} phenyl) -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(44) N- {2,5-Difluoro-4--4-[(2-{[(4-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1, 1-dicboxamide,
(45) N- {4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] oxy} -2,5-difluorophenyl} -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide,
(46) N- (2,5-Difluoro-4--4-[[2-({[3- (2-dimethylaminoacetoxy) azetinin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide,
(47) N- (2,5-Difluoro-4--4-[[2-({[(3S) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide, and (48) N- (2,5-Difluoro-4-{[2-({[(3R) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicboxamide.
　一般式（Ｉ）における化合物の更に好適な具体例としては、以下に示す化合物をあげることができる。
（１）Ｎ－（２－Ｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（２）Ｎ－［４－（｛２－［（ａｚｅｔｉｄｉｎ－１－ｙｌｃａｒｂｏｎｙｌ）ａｍｉｎｏ］ｐｙｒｉｄｉｎ－４－ｙｌ｝ｏｘｙ）－２－ｆｌｕｏｒｏｐｈｅｎｙｌ］－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（３）Ｎ－｛２，５－Ｄｉｆｌｕｏｒｏ－４－［（２－｛［（３－ｈｙｄｒｏｘｙａｚｅｔｉｄｉｎ－１－ｙｌ）ｃａｒｂｏｎｙｌ］ａｍｉｎｏ｝ｐｙｒｉｄｉｎ－４－ｙｌ）ｏｘｙ］ｐｈｅｎｙｌ｝－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（４）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［４－（４－ｍｅｔｈｙｌｐｉｐｅｒａｚｉｎ－１－ｙｌ）ｐｉｐｅｒｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（５）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［ｍｅｔｈｙｌ（１－ｍｅｔｈｙｌｐｉｐｅｒｉｄｉｎ－４－ｙｌ）ａｍｉｎｏ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ
（６）Ｎ－（２，５－Ｄｉｆｌｕｏｒｏ－４－｛［２－（｛［３－（ｈｙｄｒｏｘｙｍｅｔｈｙｌ）ａｚｅｔｉｄｉｎ－１－ｙｌ］ｃａｒｂｏｎｙｌ｝ａｍｉｎｏ）ｐｙｒｉｄｉｎ－４－ｙｌ］ｏｘｙ｝ｐｈｅｎｙｌ）－Ｎ’－（４－ｆｌｕｏｒｏｐｈｅｎｙｌ）ｃｙｃｌｏｐｒｏｐａｎｅ－１，１－ｄｉｃａｒｂｏｘａｍｉｄｅ。 More preferred specific examples of the compound represented by the general formula (I) include the compounds shown below.
(1) N- (2-Fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1, 1-dicboxamide
(2) N- [4-({2-[(azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1- dicarboxamide
(3) N- {2,5-Difluoro-4--4-[(2-{[(3-hydroxyzetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4- fluorphenyl) cyclopropane-1,1-dicboxamide
(4) N- (2,5-Difluoro-4--4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide
(5) N- (2,5-Difluoro-4--4-[[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicboxamide
(6) N- (2,5-Difluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'- (4-fluorophenyl) cyclopropane-1,1-dicboxamide.
　なお、「置換基群から選ばれる置換基を有していてもよい」とは、置換基群に記載された置換基から任意に選択される１ないし３個の置換基を有していてもよいことを意味する。 The phrase “may have a substituent selected from the substituent group” means that it may have 1 to 3 substituents arbitrarily selected from the substituents described in the substituent group. Means good.
　本発明に係る化合物は、国際公開第２００７／０２３７６８号パンフレットの記載に基づいて製造することができる。 The compound according to the present invention can be produced based on the description in International Publication No. 2007/023768.
［薬理試験例］
　本発明に係る化合物の肝細胞増殖因子受容体阻害活性、抗腫瘍活性、血管新生阻害活性および癌転移抑制活性は、国際公開第２００７／０２３７６８号パンフレットにおいて確認されている。本発明に係る化合物の食道癌に対する作用を以下の方法に従い評価した。 [Pharmacological test example]
The hepatocyte growth factor receptor inhibitory activity, antitumor activity, angiogenesis inhibitory activity, and cancer metastasis suppressive activity of the compounds according to the present invention have been confirmed in WO 2007/023768. The action of the compound according to the present invention on esophageal cancer was evaluated according to the following method.
　なお、以下の薬理試験例で使用される略号または用語の一覧を下記に示す。
＜略号一覧＞
ＦＢＳ（Ｆｅｔａｌ　ｂｏｖｉｎｅ　ｓｅｒｕｍ、ウシ胎児血清） A list of abbreviations or terms used in the following pharmacological test examples is shown below.
<List of abbreviations>
FBS (Fetal bovine serum)
薬理試験例１：ヒト食道癌細胞増殖に対する阻害作用
　ヒト食道癌細胞（ＯＥ１９、ＯＥ２１およびＯＥ３３）は、大日本住友製薬株式会社から購入した。ＯＥ１９、ＯＥ２１またはＯＥ３３を、１０％ＦＢＳを含むＲＰＭＩ１６４０培地（Ｓｉｇｍａ社より購入）に懸濁した。その細胞懸濁液（２×１０４個／ｍｌ）を細胞培養用９６ウェルプレート（ＦＡＬＣＯＮ社より購入、製品番号３５３０７５）に０．１ｍｌ／ｗｅｌｌ加え、５％ＣＯ２インキュベーター中（３７℃）で一晩培養した。培養後、各ウェルに１０％ＦＢＳを含むＲＰＭＩ１６４０培地で希釈した被検物質を０．１ｍｌ加えて、更に５％ＣＯ２インキュベーター中（３７℃）で３日間培養した。培養後、各ウェルにＣｅｌｌ　Ｃｏｕｎｔｉｎｇ　Ｋｉｔ－８（ＤＯＪＩＮＤＯ社より購入、製品番号３４３－０７６２３）を１０μｌ加え、５％ＣＯ２インキュベーター中（３７℃）で約２時間インキュベーションした。インキュベーション後、測定波長を４５０ｎｍ、対照波長を６６０ｎｍとして、各ウェルの吸光度をプレートリーダーＭＴＰ－５００（コロナ電気社製）を用いて測定した。被検物質を加えていないウェルの吸光度に対する被検物質を加えた各ウェルの吸光度の比率（％）を求め、この比率から細胞増殖を５０％阻害するのに必要な被検物質の濃度（ＩＣ５０；μＭ）を求めた。結果を表１に示す。 Pharmacological Test Example 1: Inhibitory action on human esophageal cancer cell proliferation Human esophageal cancer cells (OE19, OE21 and OE33) were purchased from Dainippon Sumitomo Pharma Co., Ltd. OE19, OE21 or OE33 was suspended in RPMI 1640 medium (purchased from Sigma) containing 10% FBS. The cell suspension (2 × 10 4 cells / ml) was added to a 96-well plate for cell culture (purchased from FALCON, product number 353075) at 0.1 ml / well in a 5% CO 2 incubator (37 ° C.). Incubated overnight. After culturing, 0.1 ml of a test substance diluted with RPMI 1640 medium containing 10% FBS was added to each well, and further cultured in a 5% CO 2 incubator (37 ° C.) for 3 days. After culturing, 10 μl of Cell Counting Kit-8 (purchased from DOJINDO, product number 343-07623) was added to each well and incubated in a 5% CO 2 incubator (37 ° C.) for about 2 hours. After the incubation, the measurement wavelength was 450 nm and the control wavelength was 660 nm, and the absorbance of each well was measured using a plate reader MTP-500 (manufactured by Corona Electric Co., Ltd.). The ratio (%) of the absorbance of each well to which the test substance was added to the absorbance of the well to which the test substance was not added was determined, and the concentration of the test substance (IC required to inhibit cell growth by 50% from this ratio (IC) 50 ; μM). The results are shown in Table 1.
Figure JPOXMLDOC01-appb-T000015
Figure JPOXMLDOC01-appb-T000015
　本発明に係る化合物は、優れたＨＧＦＲ阻害作用を有し、食道癌治療用組成物として有用である。 The compound according to the present invention has an excellent HGFR inhibitory action and is useful as a composition for treating esophageal cancer.

Claims (20)

  1. 　一般式
    Figure JPOXMLDOC01-appb-C000001
     　（式中、Ｒ１は、３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）または式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、同一または異なって、水素原子、Ｃ１－６アルキル基、Ｃ３－６アルケニル基、Ｃ３－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員へテロアリール基または４～１０員非芳香族ヘテロ環式基を意味する。ただし、Ｒ１１ａおよびＲ１１ｂは、下記置換基群ａまたは下記置換基群ｂから選ばれる置換基を有していてもよい。
    ［置換基群ａ］
    ハロゲン原子、水酸基、メルカプト基、ニトロ基、シアノ基およびオキソ基。
    ［置換基群ｂ］
    Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基、３～１０員非芳香族ヘテロ環式基、Ｃ１－６アルコキシ基、Ｃ３－６アルケニルオキシ基、Ｃ３－６アルキニルオキシ基、Ｃ３－１０シクロアルコキシ基、Ｃ６－１０アリールオキシ基、５～１０員ヘテロアリールオキシ基、４～１０員非芳香族ヘテロ環オキシ基、Ｃ１－６アルキルチオ基、Ｃ３－６アルケニルチオ基、Ｃ３－６アルキニルチオ基、Ｃ３－１０シクロアルキルチオ基、Ｃ６－１０アリールチオ基、５～１０員ヘテロアリールチオ基、４～１０員非芳香族ヘテロ環チオ基および式－Ｔ１－Ｔ２－Ｔ３
    　（式中、Ｔ１は、単結合またはＣ１－６アルキレン基を意味する。
    　Ｔ２は、カルボニル基、スルフィニル基、スルホニル基、式－Ｃ（＝Ｏ）－Ｏ－で表される基、式－Ｏ－Ｃ（＝Ｏ）－で表される基、式－ＳＯ２－Ｏ－で表される基、式－Ｏ－ＳＯ２－で表される基、式－ＮＲＴ１－で表される基、式－Ｃ（＝Ｏ）－ＮＲＴ１－で表される基、式－ＮＲＴ１－Ｃ（＝Ｏ）－で表される基、式－ＳＯ２－ＮＲＴ１－で表される基または式－ＮＲＴ１－ＳＯ２－で表される基を意味する。
    　Ｔ３は、水素原子、Ｃ１－６アルキル基、Ｃ３－６アルケニル基、Ｃ３－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基または４～１０員非芳香族ヘテロ環式基を意味する。
    　ＲＴ１は、水素原子またはＣ１－６アルキル基を意味する。）で表される基からなり、上記各基は、下記置換基群ｃから選ばれる置換基を有していてもよい。
    ［置換基群ｃ］
    ハロゲン原子、水酸基、メルカプト基、ニトロ基、シアノ基、オキソ基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ３－１０シクロアルキル基、Ｃ６－１０アリール基、５～１０員ヘテロアリール基、３～１０員非芳香族ヘテロ環式基、Ｃ１－６アルコキシ基、Ｃ１－６アルキルチオ基、モノ－Ｃ１－６アルキルアミノ基およびジ－Ｃ１－６アルキルアミノ基。）で表される基を意味する。
    　ただし、Ｒ１は、上記置換基群ａまたは上記置換基群ｂから選ばれる置換基を有していてもよい。
    　Ｒ２およびＲ３は、水素原子を意味する。
    　Ｒ４、Ｒ５、Ｒ６およびＲ７は、同一または異なって、水素原子、ハロゲン原子、水酸基、シアノ基、トリフルオロメチル基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基、ジ－Ｃ１－６アルキルアミノ基、式－ＣＯ－Ｒ１２（式中、Ｒ１２は、水素原子、水酸基、Ｃ１－６アルキル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基またはジ－Ｃ１－６アルキルアミノ基を意味する。）で表される基を意味する。
    　Ｒ８は、水素原子またはＣ１－６アルキル基を意味する。
    　Ｒ９は、３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）または式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、上記定義と同意義を意味する）で表される基で表される基を意味する。
    　ただし、Ｒ９は、上記置換基群ａまたは上記置換基群ｂから選ばれる置換基を有していてもよい。
    　ｎは、１ないし２の整数を意味する。
    　Ｘは、式－Ｃ（Ｒ１０）＝（式中、Ｒ１０は、水素原子、ハロゲン原子、シアノ基、Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、式－ＣＯ－Ｒ１２（式中、Ｒ１２は、上記定義と同意義を意味する。）で表される基を意味する。）で表される基または窒素原子を意味する。）
    で表される化合物もしくはその塩それらの水和物を含有する食道癌治療用組成物。     General formula
    Figure JPOXMLDOC01-appb-C000001
     (In the formula, R 1 is a 3- to 10-membered non-aromatic heterocyclic group (provided that a nitrogen atom is necessarily contained in the atoms constituting the ring and a bond is out of the nitrogen atom) ) Or formula —NR 11a R 11b (wherein R 11a and R 11b are the same or different and represent a hydrogen atom, a C 1-6 alkyl group, a C 3-6 alkenyl group, a C 3-6 alkynyl group, C 3) Means a -10 cycloalkyl group, a C 6-10 aryl group, a 5- to 10-membered heteroaryl group or a 4- to 10-membered non-aromatic heterocyclic group, provided that R 11a and R 11b represent the following substituent group a Or you may have a substituent chosen from the following substituent group b.
    [Substituent group a]
    A halogen atom, a hydroxyl group, a mercapto group, a nitro group, a cyano group and an oxo group;
    [Substituent group b]
    C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-10 cycloalkyl group, C 6-10 aryl group, 5-10 membered heteroaryl group, 3-10 membered non-aromatic Heterocyclic group, C 1-6 alkoxy group, C 3-6 alkenyloxy group, C 3-6 alkynyloxy group, C 3-10 cycloalkoxy group, C 6-10 aryloxy group, 5-10 membered hetero Aryloxy group, 4- to 10-membered non-aromatic heterocyclic oxy group, C 1-6 alkylthio group, C 3-6 alkenylthio group, C 3-6 alkynylthio group, C 3-10 cycloalkylthio group, C 6- A 10 arylthio group, a 5-10 membered heteroarylthio group, a 4-10 membered non-aromatic heterocyclic thio group and the formula -T 1 -T 2 -T 3
    (Wherein T 1 represents a single bond or a C 1-6 alkylene group).
    T 2 is a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula —C (═O) —O—, a group represented by the formula —O—C (═O) —, or a formula —SO 2 —. A group represented by the formula O—, a group represented by the formula —O—SO 2 —, a group represented by the formula —NR T1 —, a group represented by the formula —C (═O) —NR T1 —, a formula It means a group represented by —NR T1 —C (═O) —, a group represented by the formula —SO 2 —NR T1 — or a group represented by the formula —NR T1 —SO 2 —.
    T 3 is a hydrogen atom, a C 1-6 alkyl group, a C 3-6 alkenyl group, a C 3-6 alkynyl group, a C 3-10 cycloalkyl group, a C 6-10 aryl group, or a 5-10 membered heteroaryl group Or a 4- to 10-membered non-aromatic heterocyclic group.
    R T1 means a hydrogen atom or a C 1-6 alkyl group. ), And each of the above groups may have a substituent selected from the following substituent group c.
    [Substituent group c]
    Halogen atom, hydroxyl group, mercapto group, nitro group, cyano group, oxo group, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-10 cycloalkyl group, C 6-10 Aryl group, 5-10 membered heteroaryl group, 3-10 membered non-aromatic heterocyclic group, C 1-6 alkoxy group, C 1-6 alkylthio group, mono-C 1-6 alkylamino group and di-C 1-6 alkylamino groups. ).
    However, R 1 may have a substituent selected from the substituent group a or the substituent group b.
    R 2 and R 3 represent a hydrogen atom.
    R 4 , R 5 , R 6 and R 7 are the same or different and are a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a trifluoromethyl group, a C 1-6 alkyl group, a C 2-6 alkenyl group, C 2 -6 alkynyl group, C 1-6 alkoxy group, amino group, mono-C 1-6 alkylamino group, di-C 1-6 alkylamino group, formula —CO—R 12 wherein R 12 is hydrogen An atom, a hydroxyl group, a C 1-6 alkyl group, a C 1-6 alkoxy group, an amino group, a mono-C 1-6 alkylamino group or a di-C 1-6 alkylamino group). Means.
    R 8 represents a hydrogen atom or a C 1-6 alkyl group.
    R 9 represents a 3- to 10-membered non-aromatic heterocyclic group (provided that a nitrogen atom is necessarily contained in the atoms constituting the ring and a bond is drawn from the nitrogen atom) or a formula — A group represented by a group represented by NR 11a R 11b (wherein R 11a and R 11b have the same meanings as defined above).
    However, R 9 may have a substituent selected from the substituent group a or the substituent group b.
    n means an integer of 1 to 2.
    X represents the formula —C (R 10 ) = (wherein R 10 represents a hydrogen atom, a halogen atom, a cyano group, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a formula (wherein, R 12 means the the same meanings as defined.) -CO-R 12 means a group represented by.) refers to a group or a nitrogen atom represented by. )
    Or a salt thereof, or a hydrate thereof.
  2. 　Ｒ１が、上記請求項１に記載の置換基群ａまたは置換基群ｂから選ばれる置換基を有していてもよい３～１０員非芳香族ヘテロ環式基（ただし、環を構成する原子中に窒素原子が必ず含まれ、かつ窒素原子から、結合手が出ているものに限る）である請求項１記載の食道癌治療用組成物。 R 1 may have a substituent selected from the substituent group a or the substituent group b described in claim 1, and may be a 3- to 10-membered non-aromatic heterocyclic group (providing a ring) The composition for treating esophageal cancer according to claim 1, wherein the nitrogen atom is necessarily contained in the atom and the bond is out of the nitrogen atom).
  3. 　Ｒ１が、上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよい式
    Figure JPOXMLDOC01-appb-C000002
     （式中、ａは、１ないし４の整数を意味する。）で表される基または上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよい式
    Figure JPOXMLDOC01-appb-C000003
     （式中、ｂは、１ないし３の整数を意味する。Ｚは、酸素原子、硫黄原子、カルボニル基、スルホニル基または式－ＮＲＺ－（式中、ＲＺは、水素原子またはＣ１－６アルキル基を意味する。）で表される基を意味する。）で表される基である請求項１記載の食道癌治療用組成物。     R 1 may have a substituent selected from substituent group a or substituent group b according to claim 1.
    Figure JPOXMLDOC01-appb-C000002
     (Wherein, a represents an integer of 1 to 4) or a substituent selected from substituent group a or substituent group b according to claim 1. Good expression
    Figure JPOXMLDOC01-appb-C000003
     (Wherein b represents an integer of 1 to 3. Z represents an oxygen atom, a sulfur atom, a carbonyl group, a sulfonyl group, or a formula —NR Z — (wherein R Z represents a hydrogen atom or C 1- The composition for esophageal cancer treatment according to claim 1, which is a group represented by the formula:
  4. 　Ｒ１が、下記置換基群ｄから選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいピロリジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいピペリジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいアゼパン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいピペラジン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいジアゼパン－１－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいモルホリン－４－イル基、下記置換基群ｄから選ばれる置換基を有していてもよいチオモルホリン－４－イル基または下記置換基群ｄから選ばれる置換基を有していてもよい１，１－ジオキソチオモルホリン－４－イル基である請求項１記載の食道癌治療用組成物。
    ［置換基群ｄ］
    ハロゲン原子、水酸基、メルカプト基、シアノ基、ホルミル基、オキソ基、Ｃ１－６アルキル基、Ｃ３－１０シクロアルキル基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基、ジ－Ｃ１－６アルキルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジアゼパニル基および式－Ｔ４－Ｔ５　(式中、Ｔ４は、カルボニル基またはスルホニル基を意味する。Ｔ５は、Ｃ１－６アルキル基、Ｃ３－１０シクロアルキル基、アゼチジニル基、ピロリジニル基、ピペリジニル基、水酸基、Ｃ１－６アルコキシ基、アミノ基、モノ－Ｃ１－６アルキルアミノ基またはジ－Ｃ１－６アルキルアミノ基を意味する。)で表される基からなり、上記各基は、水酸基、Ｃ１－６アルキル基、ジ－Ｃ１－６アルキルアミノ基、アゼチジニル基またはピロリジニル基を有していてもよい。     R 1 may have a substituent selected from the following substituent group d, an azetidin-1-yl group, and may have a substituent selected from the following substituent group d A piperidin-1-yl group optionally having a substituent selected from the following substituent group d, an azepan-1-yl group optionally having a substituent selected from the following substituent group d, A piperazin-1-yl group optionally having a substituent selected from the following substituent group d; a diazepan-1-yl group optionally having a substituent selected from the following substituent group d; A morpholin-4-yl group optionally having a substituent selected from group d, a thiomorpholin-4-yl group optionally having a substituent selected from substituent group d below, or the following substituent 1,1-di optionally having a substituent selected from the group d The composition for treating esophageal cancer according to claim 1, which is an oxothiomorpholin-4-yl group.
    [Substituent group d]
    Halogen atom, hydroxyl group, mercapto group, cyano group, formyl group, oxo group, C 1-6 alkyl group, C 3-10 cycloalkyl group, C 1-6 alkoxy group, amino group, mono-C 1-6 alkylamino A group, a di-C 1-6 alkylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a diazepanyl group and a formula -T 4 -T 5 (wherein T 4 represents a carbonyl group or a sulfonyl group) T 5 is a C 1-6 alkyl group, C 3-10 cycloalkyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, hydroxyl group, C 1-6 alkoxy group, amino group, mono-C 1-6 alkylamino group or means a di -C 1-6 alkylamino group.) a group represented by the above each group, a hydroxyl group, C 1-6 alkyl, di -C -6 alkylamino group may have a azetidinyl or pyrrolidinyl group.
  5. 　Ｒ１が、下記置換基群ｅから選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいピロリジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいピペリジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいピペラジン－１－イル基、下記置換基群ｅから選ばれる置換基を有していてもよいジアゼパン－１－イル基または下記置換基群ｅから選ばれる置換基を有していてもよいモルホリン－４－イル基である請求項１記載の食道癌治療用組成物。
    ［置換基群ｅ］
    メチル基、エチル基、ジメチルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基およびピペラジニル基からなり、上記各基は、水酸基、メチル基、ジメチルアミノ基、アゼチジニル基、ピロリジニル基またはピペリジニル基を有していてもよい。     R 1 may have a substituent selected from the following substituent group e, azetidin-1-yl group, may have a substituent selected from the following substituent group e, pyrrolidin-1-yl A piperidin-1-yl group optionally having a substituent selected from the following substituent group e, a piperazin-1-yl group optionally having a substituent selected from the following substituent group e, A diazepan-1-yl group which may have a substituent selected from the following substituent group e or a morpholin-4-yl group which may have a substituent selected from the following substituent group e Item 5. A composition for treating esophageal cancer according to Item 1.
    [Substituent group e]
    It consists of a methyl group, an ethyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, and a piperazinyl group, and each of the above groups has a hydroxyl group, a methyl group, a dimethylamino group, an azetidinyl group, a pyrrolidinyl group, or a piperidinyl group. May be.
  6. 　Ｒ１が、下記置換基群ｇから選ばれる置換基を有していてもよいアゼチジン－１－イル基、下記置換基群ｇから選ばれる置換基を有するピロリジン－１－イル基、下記置換基群ｇから選ばれる置換基を有するピペリジン－１－イル基または下記置換基群ｇから選ばれる置換基を有するピペラジン－１－イル基である請求項１記載の食道癌治療用組成物。
    ［置換基群ｇ］
    ジメチルアミノ基、アゼチジニル基、ピロリジニル基、ピペリジニル基、ピペラジニル基、ジメチルアミノメチル基、ジメチルアミノエチル基、アゼチジン－１－イルメチル基、ピロリジン－１－イルメチル基およびピペリジン－１－イルメチル基からなり、上記各基は、メチル基またはジメチルアミノ基を有していてもよい。     R 1 represents an azetidin-1-yl group optionally having a substituent selected from the following substituent group g, a pyrrolidin-1-yl group having a substituent selected from the following substituent group g, and the following substituent The composition for treating esophageal cancer according to claim 1, which is a piperidin-1-yl group having a substituent selected from group g or a piperazin-1-yl group having a substituent selected from the following substituent group g.
    [Substituent group g]
    Consisting of dimethylamino group, azetidinyl group, pyrrolidinyl group, piperidinyl group, piperazinyl group, dimethylaminomethyl group, dimethylaminoethyl group, azetidin-1-ylmethyl group, pyrrolidin-1-ylmethyl group and piperidin-1-ylmethyl group, Each group may have a methyl group or a dimethylamino group.
  7. 　Ｒ１が、式－ＮＲ１１ａＲ１１ｂ（式中、Ｒ１１ａおよびＲ１１ｂは、上記請求項１に記載のＲ１１ａおよびＲ１１ｂと同意義を意味する。）で表される基である請求項１記載の食道癌治療用組成物。 R 1 is (wherein, R 11a and R 11b, the same meaning as R 11a and R 11b described in claim 1.) Formula -NR 11a R 11b claim a group represented by 2. A composition for treating esophageal cancer according to 1.
  8. 　Ｒ１が、式－ＮＲ１１ｃＲ１１ｄ（式中、Ｒ１１ｃは、水素原子またはＣ１－６アルキル基を意味する。Ｒ１１ｄは、Ｃ１－６アルキル基または式
    Figure JPOXMLDOC01-appb-C000004
     （式中、ｃは、１ないし３の整数を意味する。Ｚ１は、酸素原子、硫黄原子、カルボニル基、スルホニル基または式－ＮＲＺ１－（式中、ＲＺ１は、水素原子またはＣ１－６アルキル基を意味する。）で表される基を意味する。）で表される基を意味する。ただし、Ｒ１１ｄは上記請求項１に記載の置換基群ａまたは置換基群ｂから選ばれる置換基を有していてもよい。）で表される基である請求項１記載の食道癌治療用組成物。     R 1 represents a formula —NR 11c R 11d (wherein R 11c represents a hydrogen atom or a C 1-6 alkyl group. R 11d represents a C 1-6 alkyl group or a formula
    Figure JPOXMLDOC01-appb-C000004
     (Wherein c is an integer of 1 to 3. Z 1 is an oxygen atom, sulfur atom, carbonyl group, sulfonyl group or formula —NR Z1 — (wherein R Z1 is a hydrogen atom or C 1 Means a -6 alkyl group.) Means a group represented by). However, R 11d may have a substituent selected from the substituent group a or the substituent group b described in claim 1. The composition for treating esophageal cancer according to claim 1, wherein the composition is a group represented by the formula:
  9. 　Ｒ１が、式－ＮＲ１１ｅＲ１１ｆ（式中、Ｒ１１ｅは、水素原子またはＣ１－６アルキル基を意味する。Ｒ１１ｆは、Ｃ１－６アルキル基、ピロリジン－３－イル基、ピペリジン－３－イル基、ピペリジン－４－イル基またはテトラヒドロピラン－４－イル基を意味する。ただし、Ｒ１１ｆは、上記請求項４に記載の置換基群ｄから選ばれる置換基を有していてもよい。）で表される基である請求項１記載の食道癌治療用組成物。 R 1 represents the formula —NR 11e R 11f (wherein R 11e represents a hydrogen atom or a C 1-6 alkyl group. R 11f represents a C 1-6 alkyl group, a pyrrolidin-3-yl group, a piperidine) It means a -3-yl group, a piperidin-4-yl group or a tetrahydropyran-4-yl group, provided that R 11f has a substituent selected from the substituent group d described in claim 4. The composition for treating esophageal cancer according to claim 1, which is a group represented by:
  10. 　Ｒ１が、式－ＮＲ１１ｇＲ１１ｈ（式中、Ｒ１１ｇは、水素原子またはメチル基を意味する。Ｒ１１ｈは、ｎ－プロピル基、ｎ－ブチル基、ピロリジン－３－イル基、ピペリジン－３－イル基、ピペリジン－４－イル基またはテトラヒドロピラン－４－イル基を意味する。ただし、Ｒ１１ｈは、下記置換基群ｆから選ばれる置換基を有していてもよい。）で表される基である請求項１記載の食道癌治療用組成物。
    ［置換基群ｆ］
    メチル基、エチル基、ｎ－プロピル基、アセチル基、ジメチルアミノ基、ジエチルアミノ基、アゼチジニル基、ピロリジニル基およびピペラジニル基からなり、上記各基は、メチル基またはジメチルアミノ基を有していてもよい。     R 1 has the formula —NR 11g R 11h (wherein R 11g represents a hydrogen atom or a methyl group. R 11h represents an n-propyl group, an n-butyl group, a pyrrolidin-3-yl group, a piperidine- 3-yl group, piperidin-4-yl group or tetrahydropyran-4-yl group, provided that R 11h may have a substituent selected from the following substituent group f). The composition for treating esophageal cancer according to claim 1, which is a group to be treated.
    [Substituent group f]
    It consists of a methyl group, an ethyl group, an n-propyl group, an acetyl group, a dimethylamino group, a diethylamino group, an azetidinyl group, a pyrrolidinyl group, and a piperazinyl group, and each of the above groups may have a methyl group or a dimethylamino group .
  11. 　Ｒ１が、式－Ｎ（ＣＨ３）Ｒ１１ｉ（式中、Ｒ１１ｉは、ｎ－プロピル基、ｎ－ブチル基、ピロリジン－３－イル基またはピペリジン－４－イル基を意味する。ただし、Ｒ１１ｉは、下記置換基群ｈから選ばれる置換基を有する。）で表される基である請求項１記載の食道癌治療用組成物。
    ［置換基群ｈ］
    ジメチルアミノ基、ジエチルアミノ基、ジメチルアミノエチル基、ジメチルアミノプロピル基および１－メチルアゼチジン－３－イル基。     R 1 represents the formula —N (CH 3 ) R 11i (wherein R 11i represents an n-propyl group, an n-butyl group, a pyrrolidin-3-yl group, or a piperidin-4-yl group, provided that The composition for treating esophageal cancer according to claim 1, wherein R 11i has a substituent selected from the following substituent group h.
    [Substituent group h]
    Dimethylamino group, diethylamino group, dimethylaminoethyl group, dimethylaminopropyl group, and 1-methylazetidin-3-yl group.
  12. 　Ｒ１が、式－Ｎ（ＣＨ３）Ｒ１１ｊ（式中、Ｒ１１ｊは、１－メチルピペリジン－４－イル基または１－エチルピペリジン－４－イル基を意味する。）で表される基である請求項１記載の食道癌治療用組成物。 R 1 is a group represented by the formula —N (CH 3 ) R 11j (wherein R 11j represents a 1-methylpiperidin-4-yl group or a 1-ethylpiperidin-4-yl group). The composition for treating esophageal cancer according to claim 1.
  13. 　Ｒ４、Ｒ５、Ｒ６およびＲ７が、同一または異なって、水素原子、ハロゲン原子またはＣ１－６アルキル基である請求項１～１２のいずれか１項記載の食道癌治療用組成物。 The composition for treating esophageal cancer according to any one of claims 1 to 12, wherein R 4 , R 5 , R 6 and R 7 are the same or different and each is a hydrogen atom, a halogen atom or a C 1-6 alkyl group. .
  14. 　Ｒ８が、水素原子である請求項１～１３のいずれか１項記載の食道癌治療用組成物。 The composition for treating esophageal cancer according to any one of claims 1 to 13, wherein R 8 is a hydrogen atom.
  15. 　Ｘが、式－Ｃ（Ｒ１０ａ）＝（式中、Ｒ１０ａは、水素原子、ハロゲン原子またはシアノ基を意味する。）で表される基である請求項１～１４のいずれか１項記載の食道癌治療用組成物。 X is a group represented by the formula -C (R 10a ) = (wherein R 10a represents a hydrogen atom, a halogen atom or a cyano group). A composition for treating esophageal cancer.
  16. 　Ｘが、窒素原子である請求項１～１４のいずれか１項記載の食道癌治療用組成物。 The composition for treating esophageal cancer according to any one of claims 1 to 14, wherein X is a nitrogen atom.
  17. 　ｎが、１である請求項１～１６のいずれか１項記載の食道癌治療用組成物。 The composition for treating esophageal cancer according to any one of claims 1 to 16, wherein n is 1.
  18. 　Ｒ９が、上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ１－６アルキルアミノ基、上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ３－１０シクロアルキルアミノ基、上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ６－１０アリールアミノ基、上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－５～１０員へテロアリールアミノ基または上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－４～１０員非芳香族ヘテロ環アミノ基である請求項１～１７のいずれか１項記載の食道癌治療用組成物。 R 9 is a mono-C 1-6 alkylamino group which may have a substituent selected from the substituent group a or the substituent group b according to claim 1, the substituent according to claim 1 A mono-C 3-10 cycloalkylamino group which may have a substituent selected from group a or substituent b, selected from substituent group a or substituent b of claim 1 A mono-C 6-10 arylamino group which may have a substituent, and a mono-5 which may have a substituent selected from the substituent group a or the substituent group b according to claim 1 A mono-4 to 10-membered non-aromatic heterocyclic amino group optionally having a 10-membered heteroarylamino group or a substituent selected from substituent group a or substituent group b according to claim 1 The esophageal cancer according to any one of claims 1 to 17, wherein Therapeutic composition.
  19. 　Ｒ９が、上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ３－１０シクロアルキルアミノ基または上記請求項１に記載の置換基群ａもしくは置換基群ｂから選ばれる置換基を有していてもよいモノ－Ｃ６－１０アリールアミノ基である請求項１～１７のいずれか１項記載の食道癌治療用組成物。 R 9 is a mono-C 3-10 cycloalkylamino group which may have a substituent selected from the substituent group a or the substituent group b according to claim 1, or the above-mentioned claim 1. The composition for treating esophageal cancer according to any one of claims 1 to 17, which is a mono-C 6-10 arylamino group which may have a substituent selected from substituent group a or substituent group b. .
  20. 　一般式（Ｉ）で表される化合物が、
    （１）Ｎ－［４－（｛２－［（｛４－［２－（ジメチルアミノ）エチル］ピペラジン－１－イル｝カルボニル）アミノ］ピリジン－４－イル｝オキシ）－２－フルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２）Ｎ－（２－フルオロ－４－｛［２－（｛［メチル（１－メチルピペリジン－４－イル）アミノ］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３）Ｎ－（４－フルオロフェニル）－Ｎ’－｛２－フルオロ－４－［（２－｛［（４－ピロリジン－１－イルピペリジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル）オキシ］フェニル｝シクロプロパン－１，１－ジカルボキサミド、
    （４）Ｎ－［４－（｛２－［（｛４－［（ジメチルアミノ）メチル］ピペリジン－１－イル｝カルボニル）アミノ］ピリジン－４－イル｝オキシ）－２－フルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （５）Ｎ－｛４－［（２－｛［（４－アゼチジン－１－イルピペリジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル）オキシ］－２－フルオロフェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （６）Ｎ－［４－（｛２－［（｛４－［３－（ジメチルアミノ）アゼチジン－１－イル］ピペリジン－１－イル｝カルボニル）アミノ］ピリジン－４－イル｝オキシ）－２－フルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （７）Ｎ－（２－フルオロ－４－｛［２－（｛［４－（４－メチルピペラジン－１－イル）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （８）Ｎ－（２－フルオロ－４－｛［２－（｛［４－（１－メチルピペリジン－４－イル）ピペラジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （９）Ｎ－（２－フルオロ－４－｛［２－（｛［４－（１－メチルアゼチジン－３－イル）ピペラジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （１０）Ｎ－（４－｛［２－（｛［４－（ジメチルアミノ）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝－２－フルオロフェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （１１）Ｎ－（４－｛［２－（｛［４－（アゼチジン－１－イルメチル）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝－２－フルオロフェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （１２）Ｎ－（４－フルオロフェニル）－Ｎ’－（２－フルオロ－４－｛［２－（｛［４－（ピロリジン－１－イルメチル）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）シクロプロパン－１，１－ジカルボキサミド、
    （１３）Ｎ－（４－｛［２－（｛［（３Ｓ）－３－（ジメチルアミノ）ピロリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝－２－フルオロフェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （１４）Ｎ－（４－｛［２－（｛［（３Ｒ）－３－（ジメチルアミノ）ピロリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝－２－フルオロフェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （１５）Ｎ－（２－フルオロ－４－｛［２－（｛［メチル（１－メチルピペリジン－４－イル）アミノ］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－フェニルシクロプロパン－１，１－ジカルボキサミド、
    （１６）Ｎ－（２－フルオロ－４－｛［２－（｛［４－（４－メチルピペラジン－１－イル）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－フェニルシクロプロパン－１，１－ジカルボキサミド、
    （１７）Ｎ－［４－（｛２－［（｛４－［３－（ジメチルアミノ）アゼチジン－１－イル］ピペリジン－１－イル｝カルボニル）アミノ］ピリジン－４－イル｝オキシ）－２－フルオロフェニル］－Ｎ’－フェニルシクロプロパン－１，１－ジカルボキサミド、
    （１８）Ｎ－（４－｛［２－（｛［（１－エチルピペリジン－４－イル）（メチル）アミノ］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝－２－フルオロフェニル）－Ｎ’－フェニルシクロプロパン－１，１－ジカルボキサミド、
    （１９）Ｎ－［４－（｛２－［（アゼチジン－１－イルカルボニル）アミノ］ピリジン－４－イル｝オキシ）－２－フルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２０）Ｎ－（４－フルオロフェニル）－Ｎ’－［２－フルオロ－４－（｛２－［（ピロリジン－１－イルカルボニル）アミノ］ピリジン－４－イル｝オキシ）フェニル］シクロプロパン－１，１－ジカルボキサミド、
    （２１）Ｎ－｛２－フルオロ－４－［（２－｛［（３－ヒドロキシアゼチジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル）オキシ］フェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２２）Ｎ－［４－（｛２－［（１，３’－ビアゼチジン－１’－イルカルボニル）アミノ］ピリジン－４－イル｝オキシ）－２－フルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２３）Ｎ－（２－フルオロ－４－｛［２－（｛［３－（ヒドロキシメチル）アゼチジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２４）Ｎ－（４－｛［２－（｛［３－（ジメチルアミノ）アゼチジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝－２－フルオロフェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２５）Ｎ－［４－（｛２－［（｛３－［（ジメチルアミノ）メチル］アゼチジン－１－イル｝カルボニル）アミノ］ピリジン－４－イル｝オキシ）－２－フルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２６）Ｎ－｛２－フルオロ－４－［（２－｛［（４－ヒドロキシピペリジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル）オキシ］フェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２７）Ｎ－（２－フルオロ－４－｛［２－（｛［４－（ヒドロキシメチル）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２８）Ｎ－（２－フルオロ－４－｛［２－（｛［（３Ｒ）－３－ヒドロキシピロリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （２９）Ｎ－（２－フルオロ－４－｛［２－（｛［（３Ｓ）－３－ヒドロキシピロリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３０）Ｎ－［４－（｛２－［（アゼチジン－１－イルカルボニル）アミノ］ピリジン－４－イル｝オキシ）－２，５－ジフルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３１）Ｎ－｛２，５－ジフルオロ－４－［（２－｛［（３－ヒドロキシアゼチジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル）オキシ］フェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３２）Ｎ－（２，５－ジフルオロ－４－｛［２－（｛［４－（４－メチルピペラジン－１－イル）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３３）Ｎ－［２，５－ジフルオロ－４－（｛２－［（｛３－［（ジメチルアミノ）メチル］アゼチジン－１－イル｝カルボニル）アミノ］ピリジン－４－イル｝オキシ）フェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３４）Ｎ－（２，５－ジフルオロ－４－｛［２－（｛［メチル（１－メチルピペリジン－４－イル）アミノ］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３５）Ｎ－｛４－［（２－｛［３－（アゼチジン－１－イルメチル）アゼチジン－１－イルカルボニル］アミノ｝ピリジン－４－イル）オキシ］－２，５－ジフルオロフェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３６）Ｎ－（２，５－ジフルオロ－４－｛［２－（｛［３－（ヒドロキシメチル）アゼチジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３７）Ｎ－｛２，５－ジフルオロ－４－［（４－｛［（３－ヒドロキシアゼチジン－１－イル）カルボニル］アミノ｝ピリミジン－６－イル）オキシ］フェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３８）Ｎ－［４－（｛４－［（｛３－［（ジメチルアミノ）メチル］アゼチジン－１－イル｝カルボニル）アミノ］ピリミジン－６－イル｝オキシ）－２，５－ジフルオロフェニル］－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （３９）Ｎ－（２，５－ジフルオロ－４－｛［４－（｛［３－（ヒドロキシメチル）アゼチジン－１－イル］カルボニル｝アミノ）ピリミジン－６－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４０）Ｎ－（２，５－ジフルオロ－４－｛［４－（｛［メチル（１－メチルピペリジン－４－イル）アミノ］カルボニル｝アミノ）ピリミジン－６－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４１）Ｎ－（２，５－ジフルオロ－４－｛［４－（｛［４－（４－メチルピペラジン－１－イル）ピペリジン－１－イル］カルボニル｝アミノ）ピリミジン－６－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４２）Ｎ－（４－｛［２－（｛［４－（ジメチルアミノ）ピペリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝－２，５－ジフルオロフェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４３）Ｎ－｛２，５－ジフルオロ－４－［（２－｛［（４－メチルピペラジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４４）Ｎ－｛２，５－ジフルオロ－４－［（２－｛［（４－ヒドロキシピペリジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル）オキシ］フェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４５）Ｎ－｛４－［（２－｛［（４－アゼチジン－１－イルピペリジン－１－イル）カルボニル］アミノ｝ピリジン－４－イル）オキシ］オキシ｝－２，５－ジフルオロフェニル｝－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４６）Ｎ－（２，５－ジフルオロ－４－｛［２－（｛［３－（２－ジメチルアミノアセトキシ）アゼチジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミド、
    （４７）Ｎ－（２，５－ジフルオロ－４－｛［２－（｛［（３Ｓ）－３－ヒドロキシピロリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミドまたは
    （４８）Ｎ－（２，５－ジフルオロ－４－｛［２－（｛［（３Ｒ）－３－ヒドロキシピロリジン－１－イル］カルボニル｝アミノ）ピリジン－４－イル］オキシ｝フェニル）－Ｎ’－（４－フルオロフェニル）シクロプロパン－１，１－ジカルボキサミドである請求項１記載の食道癌治療用組成物。     The compound represented by the general formula (I) is:
    (1) N- [4-({2-[({4- [2- (dimethylamino) ethyl] piperazin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (2) N- (2-fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N'- (4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (3) N- (4-Fluorophenyl) -N ′-{2-fluoro-4-[(2-{[(4-pyrrolidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridine-4- Yl) oxy] phenyl} cyclopropane-1,1-dicarboxamide,
    (4) N- [4-({2-[({4-[(Dimethylamino) methyl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (5) N- {4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] -2-fluorophenyl} -N′- (4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (6) N- [4-({2-[({4- [3- (Dimethylamino) azetidin-1-yl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2 -Fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (7) N- (2-fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl ) —N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (8) N- (2-Fluoro-4-{[2-({[4- (1-methylpiperidin-4-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl ) —N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (9) N- (2-Fluoro-4-{[2-({[4- (1-methylazetidin-3-yl) piperazin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} Phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (10) N- (4-{[2-({[4- (Dimethylamino) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (11) N- (4-{[2-({[4- (azetidin-1-ylmethyl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (12) N- (4-Fluorophenyl) -N ′-(2-fluoro-4-{[2-({[4- (pyrrolidin-1-ylmethyl) piperidin-1-yl] carbonyl} amino) pyridine- 4-yl] oxy} phenyl) cyclopropane-1,1-dicarboxamide,
    (13) N- (4-{[2-({[(3S) -3- (dimethylamino) pyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl)- N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (14) N- (4-{[2-({[(3R) -3- (dimethylamino) pyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl)- N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (15) N- (2-Fluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N′- Phenylcyclopropane-1,1-dicarboxamide,
    (16) N- (2-fluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl ) —N′-phenylcyclopropane-1,1-dicarboxamide,
    (17) N- [4-({2-[({4- [3- (Dimethylamino) azetidin-1-yl] piperidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2 -Fluorophenyl] -N'-phenylcyclopropane-1,1-dicarboxamide,
    (18) N- (4-{[2-({[(1-Ethylpiperidin-4-yl) (methyl) amino] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N '-Phenylcyclopropane-1,1-dicarboxamide,
    (19) N- [4-({2-[(azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4-fluorophenyl) cyclopropane- 1,1-dicarboxamide,
    (20) N- (4-Fluorophenyl) -N ′-[2-fluoro-4-({2-[(pyrrolidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) phenyl] cyclopropane- 1,1-dicarboxamide,
    (21) N- {2-fluoro-4-[(2-{[(3-hydroxyazetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4- Fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (22) N- [4-({2-[(1,3′-Biazetidin-1′-ylcarbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N ′-(4- Fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (23) N- (2-Fluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (24) N- (4-{[2-({[3- (Dimethylamino) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2-fluorophenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (25) N- [4-({2-[({3-[(Dimethylamino) methyl] azetidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) -2-fluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (26) N- {2-fluoro-4-[(2-{[(4-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4-fluoro Phenyl) cyclopropane-1,1-dicarboxamide,
    (27) N- (2-Fluoro-4-{[2-({[4- (hydroxymethyl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (28) N- (2-fluoro-4-{[2-({[(3R) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N′- (4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (29) N- (2-fluoro-4-{[2-({[(3S) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N′- (4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (30) N- [4-({2-[(azetidin-1-ylcarbonyl) amino] pyridin-4-yl} oxy) -2,5-difluorophenyl] -N ′-(4-fluorophenyl) cyclo Propane-1,1-dicarboxamide,
    (31) N- {2,5-difluoro-4-[(2-{[(3-hydroxyazetidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (32) N- (2,5-difluoro-4-{[2-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy } Phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (33) N- [2,5-difluoro-4-({2-[({3-[(dimethylamino) methyl] azetidin-1-yl} carbonyl) amino] pyridin-4-yl} oxy) phenyl] -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (34) N- (2,5-difluoro-4-{[2-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (35) N- {4-[(2-{[3- (azetidin-1-ylmethyl) azetidin-1-ylcarbonyl] amino} pyridin-4-yl) oxy] -2,5-difluorophenyl} -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (36) N- (2,5-difluoro-4-{[2-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (37) N- {2,5-difluoro-4-[(4-{[(3-hydroxyazetidin-1-yl) carbonyl] amino} pyrimidin-6-yl) oxy] phenyl} -N ′-( 4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (38) N- [4-({4-[({3-[(Dimethylamino) methyl] azetidin-1-yl} carbonyl) amino] pyrimidin-6-yl} oxy) -2,5-difluorophenyl] -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (39) N- (2,5-difluoro-4-{[4-({[3- (hydroxymethyl) azetidin-1-yl] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (40) N- (2,5-difluoro-4-{[4-({[methyl (1-methylpiperidin-4-yl) amino] carbonyl} amino) pyrimidin-6-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (41) N- (2,5-difluoro-4-{[4-({[4- (4-methylpiperazin-1-yl) piperidin-1-yl] carbonyl} amino) pyrimidin-6-yl] oxy } Phenyl) -N ′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (42) N- (4-{[2-({[4- (Dimethylamino) piperidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} -2,5-difluorophenyl) -N ′ -(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (43) N- {2,5-difluoro-4-[(2-{[(4-methylpiperazin-1-yl) carbonyl] amino} pyridin-4-yl] oxy} phenyl) -N ′-(4 -Fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (44) N- {2,5-difluoro-4-[(2-{[(4-hydroxypiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] phenyl} -N ′-(4 -Fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (45) N- {4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl) carbonyl] amino} pyridin-4-yl) oxy] oxy} -2,5-difluorophenyl} -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (46) N- (2,5-difluoro-4-{[2-({[3- (2-dimethylaminoacetoxy) azetidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide,
    (47) N- (2,5-difluoro-4-{[2-({[(3S) -3-hydroxypyrrolidin-1-yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-Fluorophenyl) cyclopropane-1,1-dicarboxamide or (48) N- (2,5-difluoro-4-{[2-({[(3R) -3-hydroxypyrrolidine-1- The composition for treating esophageal cancer according to claim 1, which is yl] carbonyl} amino) pyridin-4-yl] oxy} phenyl) -N '-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide.
PCT/JP2008/071881 2008-12-02 2008-12-02 Composition for treatment of esophageal cancer WO2010064300A1 (en)

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