Fused heteroaryl compounds and their use as CaMKII inhibitors

Abstract

The present invention provides fused heteroaryl compounds having CaMKII inhibitory activity, which are expected to be useful as drugs for the prevention or treatment of heart diseases (particularly catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmia). The present invention relates to a compound of formula (I): JPEG2023543038000104.jpg5175 (wherein each symbol is as defined in the specification). or a pharmaceutically acceptable salt thereof.

Description

[Technical Field]

[0001] Technical Field The present invention relates to fused heteroaryl compounds having calcium / calmodulin-dependent protein kinase II (sometimes abbreviated as "CaMKII" in this specification) inhibitory activity, which are expected to be useful as drugs for the prevention or treatment of heart diseases (particularly catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, fatal arrhythmias, etc.). [Background technology]

[0002] Heart disease includes heart failure, arrhythmia, myocardial infarction, angina, valvular heart disease, etc., and is a disease with a high mortality rate. In the treatment of heart disease with drugs, symptoms are improved by controlling each risk factor and by treating symptoms. However, satisfaction with treatment remains low, and there is currently no cure.

[0003] The calcium-calmodulin complex is a Ca receptor involved in serine / threonine protein kinases. 2+ It binds to calmodulin-dependent protein kinase (CaMK) and activates the kinase. The CaMK family includes CaMKII, and four isoforms (α, β, γ, and δ) exist as CaMKII. CaMKII α and CaMKII β are mainly expressed in brain tissue, while CaMKII γ and CaMKII δ are expressed in many tissues, including the heart. In addition to binding of calcium-calmodulin complexes, CaMKII is activated by amino acid modifications due to oxidative stress or hyperglycemia. Upon kinase activation, CaMKII binds to its substrate, the transcription factor Ca 2+ They regulate cellular functions through phosphorylation of proteins that function in organelle uptake / excretion, proteins that control muscle contraction and relaxation, and channels that control intracellular ion concentrations.

[0004] Several publications suggest that CaMKII plays a detrimental role in the progression of cardiac disease. CaMKII expression and activity are increased in the hearts of human patients or animals with heart failure (Non-Patent Documents 1-4). Transgenic mice overexpressing CaMKII δ in the heart have been reported to develop cardiac hypertrophy and heart failure (Non-Patent Document 4). Studies using inhibitors by pharmacological methods and studies using gene deletion by genetic methods have reported protective effects against heart failure, cardiac hypertrophy, myocardial infarction, and arrhythmias in mice by inhibiting CaMKII and overexpressing CaMKII inhibitory proteins (Non-Patent Documents 5-7). Regarding catecholamine-induced polymorphic ventricular tachycardia, mutant ryanodine knock-in mice (RyR2 R4496C+ / - It has been reported that CaMKII inhibitors improve disease conditions in mice (Non-Patent Document 8). These findings suggest the effectiveness of CaMKII inhibitors in the prevention and / or treatment of heart diseases, including heart failure, cardiac hypertrophy, myocardial infarction, and arrhythmia.

[0005] Recently, the exacerbating effect of CaMKII on the growth or metastasis of certain types of cancer has been suggested (Non-Patent Document 9). Furthermore, the therapeutic effect of CaMKII inhibition on acute renal failure, intimal hyperplasia, liver fibrosis, stroke, pain, rheumatoid arthritis, etc. has also been suggested (Non-Patent Documents 10 to 15).

[0006] However, genetic methods only achieve protein deletion or overexpression of inhibitory proteins, which is a different mechanism from the temporary inhibition of kinase activity, and therefore, the effectiveness of kinase inhibitors cannot always be expected. Furthermore, previously reported inhibitors have low kinase selectivity for CaMKII or are not suitable for oral or chronic administration, making them unsuitable for pharmaceutical application as CaMKII-selective inhibitors.

[0007] The following compounds are known as heterocyclic compounds. Patent Document 1 discloses a compound represented by the following formula (I): [ka] (wherein each symbol is defined in Patent Document 1.) It is described that the compound is an FLT3 inhibitor and is useful for treating acute myeloid leukemia and the like.

[0008] Patent Document 2 discloses a compound of the following formula (I): [ka] (wherein each symbol is defined in Patent Document 2.) are described as being inhibitors of Syk (spleen tyrosine kinase) and useful in the treatment of diseases or conditions mediated by Syk (eg, rheumatoid arthritis).

[0009] Patent Document 3 discloses a compound of the following formula (I): [ka] (wherein each symbol is defined in Patent Document 3.) are described as mGluR (metabotropic glutamate receptor) 5 modulators and useful for treating or preventing diseases or conditions in which mGluR5 is involved (e.g., pain disorders, anxiety, depression, Alzheimer's disease, Parkinson's disease, etc.).

[0010] Patent Document 4 discloses a compound of the following formula (I): [ka] (wherein each symbol is defined in Patent Document 4).) It is described that the compound is a kinase inhibitor (particularly an inhibitor of the kinase domain in the VEGF receptor (VEGF receptor tyrosine kinase inhibitor)) and is useful for treating vascular abnormalities, tumors, diabetic retinopathy, rheumatism, endometriosis, psoriasis, etc.

[0011] Patent Document 5 discloses a compound of the following formula (I): [ka] (wherein each symbol is defined in Patent Document 5.) It is described that the compound of the formula (I) is a kinase (such as p38 kinase) inhibitor and is useful for reducing ischemic cell death (particularly for reducing traumatic neuronal cell death).

[0012] Patent Document 6 discloses a compound represented by the following formula (I): [ka] (wherein each symbol is defined in Patent Document 6.) are described as calcium / calmodulin-dependent protein kinase II inhibitors and useful in the prevention or treatment of heart disease. [Prior art documents] [Patent documents]

[0013] [Patent Document 1] WO2013 / 157540 [Patent Document 2] WO2013 / 052394 [Patent Document 3] WO2005 / 021529 [Patent Document 4] WO2002 / 024681 [Patent Document 5] WO2002 / 011724 [Patent Document 6] WO2018 / 183112 [Non-patent literature]

[0014] [Non-Patent Document 1] European Journal of Heart Failure, vol.16, p.1292-1300 [Non-patent document 2] Circulation Research, vol.84, p.713-721 [Non-patent document 3] Molecular Endocrinology, vol.17, p.183-192 [Non-patent document 4] Circulation Research, vol.92, p.912-919

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Non-Patent Document 10

Non-Patent Document 11

Non-Patent Document 12

Non-Patent Document 13

Non-Patent Document 14

Non-Patent Document 15

Summary of the Invention

Problems to be Solved by the Invention

[0015] An object of the present invention is to provide fused heteroaryl compounds having CaMKII inhibitory activity, which are expected to be useful as drugs for the prevention or treatment of heart diseases (particularly catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, fatal arrhythmia) and the like. [Means for solving the problem]

[0016] The present inventors have conducted intensive research in an attempt to solve the above-mentioned problems, and have discovered that the compound of the following formula (I) has CaMKII inhibitory activity and is therefore expected to be useful as a drug for the prevention or treatment of heart diseases (particularly catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, fatal arrhythmia), etc., leading to the completion of the present invention.

[0017] Thus, the present invention provides: [1] Formula (I): [ka] [During the ceremony, X 1 is N or CR X1 where R X1 is a hydrogen atom, halogen atom or C 1-6 is an alkyl group; X 2 , X 3 and X 4 are each independently C or N, and X 2 , X 3 and X 4 one is N and the other two are C; X 5 is N or CR X5 where R X5 is a hydrogen atom; X 6 is N or CR X6 where R X6 is a hydrogen atom; Ring A 1 is optionally further substituted C 6-14an aromatic hydrocarbon, an optionally further substituted aromatic heterocycle, or an optionally further substituted non-aromatic heterocycle, each of which is optionally fused to an optionally substituted 5- or 6-membered ring; Y 1 is N or CR Y1 where R Y1 is a hydrogen atom; Y 2 is N or CR Y2 where R Y2 is a hydrogen atom, a halogen atom or a cyano group; Y 3 is N or CR Y3 where R Y3 is a hydrogen atom or a halogen atom; Y 4 is N or CR Y4 where R Y4 is a hydrogen atom or a halogen atom; Ring B 1 is an optionally further substituted aromatic heterocycle; V is O, S, S(O), S(O)2 or N(R V ), where R V is a hydrogen atom or an optionally substituted C 1-6 is an alkyl group; and Z is an optionally substituted C 1-6 It is an alkylene group. or a pharmaceutically acceptable salt thereof (hereinafter sometimes referred to as Compound (I)).

[0018] [2] The compound of [1] above, wherein V is O, or a pharmaceutically acceptable salt thereof. [3] Ring B 1 The compound of the above [1], wherein is an optionally further substituted 5-membered aromatic heterocycle, or a pharmaceutically acceptable salt thereof. [4] The compound of [1] above, wherein Z is an optionally substituted ethylene group, or a pharmaceutically acceptable salt thereof. [5] X 5 The compound of the above [1] or a pharmaceutically acceptable salt thereof, wherein [6] X 6 The compound of the above [1] or a pharmaceutically acceptable salt thereof, wherein is CH. [7] Y 1 , Y 2 , Y 3 and Y 4 The compound or pharmaceutically acceptable salt thereof according to [1] above, wherein at least one of the following is N.

[0019] [8] Formula (I-1): [ka] (wherein each symbol is as defined in [1] above).) or a pharmaceutically acceptable salt thereof (herein also referred to as compound (I-1)).

[0020] [9] Formula (II): [ka] [During the ceremony, X 1 is N or CR X1 where R X1 is a hydrogen atom, halogen atom or C 1-6 is an alkyl group; X 2 , X 3 and X 4 are each independently C or N, and X 2 , X 3 and X 4 one is N and the other two are C; Ring A 2 is an optionally further substituted benzene ring, an optionally further substituted 5- or 6-membered aromatic heterocycle, or an optionally further substituted 5- or 6-membered non-aromatic heterocycle, each of which is optionally fused to an optionally substituted 5- or 6-membered ring; Y 1 is N or CR Y1 where R Y1 is a hydrogen atom; Y 2 is N or CR Y2 where R Y2 is a hydrogen atom, a halogen atom or a cyano group; Y 3 is N or CR Y3 where R Y3 is a hydrogen atom or a halogen atom; Y 4 is N or CR Y4 where R Y4 is a hydrogen atom or a halogen atom; Ring B 2 is an optionally further substituted 5-membered aromatic heterocycle; and R 1 is C 1-6 is an alkyl group. or a pharmaceutically acceptable salt thereof (sometimes referred to herein as Compound (II)).

[0021]

[10] X 1 The compound or pharmaceutically acceptable salt thereof according to [9] above, wherein is CH.

[11] Ring B 2 is a tetrazole or triazole, each of which is bonded at its nitrogen, or a pharmaceutically acceptable salt thereof.

[12] R 1 The compound or pharmaceutically acceptable salt thereof according to [9] above, wherein is methyl.

[13] Ring A 2 is a benzene ring, a 6-membered aromatic heterocycle, or a 6-membered non-aromatic heterocycle, each of which is further substituted with one cyano group, or a pharmaceutically acceptable salt thereof.

[14] Y 1 , Y 2 , Y 3 and Y 4 The compound or pharmaceutically acceptable salt thereof according to [9] above, wherein at least one of the following is N.

[0022]

[15] Formula (II-1): [ka] (wherein each symbol is as defined in [9] above).) or a pharmaceutically acceptable salt thereof (herein also referred to as compound (II-1)).

[0023]

[16] Formula (III): [ka] X 2 , X 3 and X 4 are each independently C or N, and X 2 , X 3 and X 4 one is N and the other two are C; Ring A 3 is an optionally further substituted benzene ring, an optionally further substituted 6-membered nitrogen-containing aromatic heterocycle, or an optionally further substituted 6-membered nitrogen-containing non-aromatic heterocycle; Y 1 is N or CR Y1 where R Y1 is a hydrogen atom; Y 2 is N or CR Y2 where R Y2 is a hydrogen atom, a halogen atom or a cyano group; Y 3 is N or CR Y3 where R Y3 is a hydrogen atom or a halogen atom; Y 4 is N or CR Y4 where R Y4 is a hydrogen atom or a halogen atom; and W is N or CH. or a pharmaceutically acceptable salt thereof (sometimes referred to herein as Compound (III)).

[0024]

[17] Formula; [ka] The substructure represented by Formula (A 3 -1)~(A 3 -9); [ka] [During the ceremony, Q 1 is N or CR Q1 where R Q1 teeth (a) a hydrogen atom, (b) a cyano group, (c) a halogen atom, (d) a hydroxy group, (e) a carboxy group, (f) amino group, (g) optionally substituted C 1-6 alkyl groups, (h) optionally substituted C 1-6 alkoxy groups, (I C 1-6 alkyl-carbonyl groups, (j) C 1-6 alkoxy-carbonyl groups, (k) optionally substituted mono- or di-C 1-6 alkylamino groups, (l) optionally substituted mono- or di-C 1-6 alkyl-carbonylamino groups, (m) Mono- or Di-C 1-6 alkoxy-carbonylamino groups, (n) Mono- or Di-C 1-6 alkyl-carbamoyl groups, (o) The-C 1-6 alkylsulfinylideneamino group, (p) C 3-10 cycloalkyl groups, (q) optionally substituted C 3-10 cycloalkyloxy groups, (r) a 3- to 8-membered monocyclic non-aromatic heterocyclic group, (s) optionally substituted 3- to 8-membered monocyclic non-aromatic heterocyclyloxy; (t) an optionally substituted 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group or (u) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group and Q 2 is N or CR Q2 where R Q2 teeth (a) a hydrogen atom, (b) a halogen atom or (c) C 1-6 alkoxy group and Q 3 is N or CR Q3 where R Q3 teeth (a) a hydrogen atom, (b) a cyano group, (c) a halogen atom, (d) a carboxy group, (e) optionally substituted C 1-6 alkyl groups, (f) optionally substituted C 1-6 alkoxy groups, (g) C 1-6 alkyl-carbonyl groups, (h) C 1-6 alkoxy-carbonyl groups, (i) Mono- or di-C 1-6 alkylamino groups, (j) optionally substituted mono- or di-C 1-6 alkyl-carbamoyl groups, (k) Ji-C 1-6 Alkyl sulfinylidene amino group or (l) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group and Q 4 is N or CR Q4 where R Q4 teeth (a) a hydrogen atom or (b) Halogen atoms and Q 1 , Q 2 , Q 3 and Q 4 wherein each N is optionally oxidized; R N1 is a hydrogen atom or C 1-6 is an alkyl group; R N2 is a hydrogen atom or C 1-6 is an alkyl group; R N3 is a hydrogen atom or C 1-6 is an alkyl group; and R N4 is a C optionally substituted with a hydrogen atom or 1 to 3 halogen atoms 1-6 is an alkyl group. The compound of the above

[16] , which is a partial structure represented by the following formula: or a pharmaceutically acceptable salt thereof.

[18] Y 1 , Y 2 , Y 3 and Y 4 wherein at least one of is N, the compound or pharmaceutically acceptable salt thereof according to

[16] .

[0025]

[19] Formula (III-1): [ka] (wherein each symbol is as defined in

[16] above.) or a pharmaceutically acceptable salt thereof (herein also referred to as compound (III-1)).

[0026]

[20] 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile, 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]pyridine-3-carbonitrile, 2-[6-(3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]pyridine-3-carbonitrile, 2-[5-(3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile, 4-fluoro-2-[6-(5-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-3-yl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile, 4-methoxy-2-[6-(3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]pyridine-3-carbonitrile, 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]-4-methoxypyridine-3-carbonitrile, 4-fluoro-2-[5-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl]benzonitrile, 4-fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyrazin-2-yl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile, 4-Fluoro-2-methoxy-6-[5-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl]benzonitrile and 4-fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-2-yl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

[0027]

[21] A pharmaceutical comprising the compound of [1] above or a pharmaceutically acceptable salt thereof.

[22] The pharmaceutical agent according to

[21] above, which is a calcium / calmodulin-dependent protein kinase II inhibitor.

[23] The pharmaceutical agent according to

[21] above, which is a drug for preventing or treating heart disease.

[24] The pharmaceutical agent according to

[23] above, wherein the cardiac disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmia.

[0028]

[25] The compound or pharmaceutically acceptable salt thereof according to [1] above for use in the prevention or treatment of heart disease.

[26] The compound or pharmaceutically acceptable salt of

[25] above, wherein the cardiac disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmia.

[0029]

[27] A method for inhibiting calcium / calmodulin-dependent protein kinase II in a mammal, comprising administering to the mammal an effective amount of the compound of [1] above or a pharmaceutically acceptable salt thereof.

[28] A method for preventing or treating heart disease in a mammal, comprising administering to the mammal an effective amount of the compound of [1] above or a pharmaceutically acceptable salt thereof.

[29] The method of

[28] above, wherein the cardiac disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmia.

[0030]

[30] Use of the compound or a pharmaceutically acceptable salt thereof according to [1] above for the manufacture of a medicament for the prevention or treatment of heart disease.

[31] The use of the above

[30] , wherein the cardiac disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmia. [Effects of the Invention]

[0031] The present invention can provide fused heteroaryl compounds having excellent CaMKII inhibitory activity, which are expected to be useful as drugs for the prevention or treatment of heart diseases (particularly catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, fatal arrhythmia) and the like. DETAILED DESCRIPTION OF THE INVENTION

[0032] Detailed Description of the Invention The present invention will be described in detail below.

[0033] The definition of each substituent used in this specification is described in detail below. Unless otherwise specified, each substituent has the following definition. In this specification, examples of the "halogen atom" include fluorine, chlorine, bromine and iodine, which contain, in addition to carbon atoms, 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms and oxygen atoms as ring-constituting atoms. As used herein, "C 1-6 Examples of "alkyl groups" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, and 2-ethylbutyl. As used herein, "optionally halogenated C 1-6 Examples of the "alkyl group" include C 1-6Include alkyl groups, specific examples of which include methyl, chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, ethyl, 2-bromoethyl, 2,2,2-trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, propyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, isopropyl, butyl, 4,4,4-trifluorobutyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 5,5,5-trifluoropentyl, hexyl, and 6,6,6-trifluorohexyl. As used herein, "C 2-6 Examples of "alkenyl groups" include ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl and 5-hexenyl. As used herein, "C 2-6 Examples of "alkynyl groups" include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, and 4-methyl-2-pentynyl. As used herein, "C 3-10 Examples of "cycloalkyl groups" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, and adamantyl. As used herein, "optionally halogenated C 3-10 Examples of "cycloalkyl groups" include C groups optionally containing 1 to 7, preferably 1 to 5, halogen atoms. 3-10Included are cycloalkyl groups, specific examples of which include cyclopropyl, 2,2-difluorocyclopropyl, 2,3-difluorocyclopropyl, cyclobutyl, difluorocyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. As used herein, "C 3-10 Examples of "cycloalkenyl groups" include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. As used herein, "C 6-14 Examples of the "aryl group" include phenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl and 9-anthryl. As used herein, "C 7-16 Examples of the "aralkyl group" include benzyl, phenethyl, naphthylmethyl and phenylpropyl.

[0034] As used herein, "C 1-6 Examples of "alkoxy groups" include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy. As used herein, "optionally halogenated C 1-6 Examples of the "alkoxy group" include C alkyl groups optionally containing 1 to 7, preferably 1 to 5, halogen atoms. 1-6 Specific examples include alkoxy groups, such as methoxy, difluoromethoxy, trifluoromethoxy, ethoxy, 2,2,2-trifluoroethoxy, propoxy, isopropoxy, butoxy, 4,4,4-trifluorobutoxy, isobutoxy, sec-butoxy, pentyloxy, and hexyloxy. As used herein, "C 3-10 Examples of the "cycloalkyloxy group" include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy and cyclooctyloxy. As used herein, "C 1-6Examples of the "alkylthio group" include methylthio, ethylthio, propylthio, isopropylthio, butylthio, sec-butylthio, tert-butylthio, pentylthio and hexylthio. As used herein, "optionally halogenated C 1-6 Examples of the "alkylthio group" include C alkylthio groups optionally having 1 to 7, preferably 1 to 5, halogen atoms. 1-6 Specific examples of alkylthio groups include methylthio, difluoromethylthio, trifluoromethylthio, ethylthio, propylthio, isopropylthio, butylthio, 4,4,4-trifluorobutylthio, pentylthio, and hexylthio. As used herein, "C 1-6 Examples of "alkyl-carbonyl groups" include acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 3-methylbutanoyl, 2-methylbutanoyl, 2,2-dimethylpropanoyl, hexanoyl and heptanoyl. As used herein, "optionally halogenated C 1-6 Examples of "alkyl-carbonyl group" include C alkyl-carbonyl groups optionally containing 1 to 7, preferably 1 to 5, halogen atoms. 1-6 It includes alkyl-carbonyl groups, specific examples of which include acetyl, chloroacetyl, trifluoroacetyl, trichloroacetyl, propanoyl, butanoyl, pentanoyl and hexanoyl. As used herein, "C 1-6 Examples of "alkoxy-carbonyl groups" include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl. As used herein, "C 6-14 Examples of the "aryl-carbonyl group" include benzoyl, 1-naphthoyl and 2-naphthoyl. As used herein, "C 7-16 Examples of the "aralkyl-carbonyl group" include phenylacetyl and phenylpropionyl. In the present specification, examples of the "5- to 14-membered aromatic heterocyclylcarbonyl group" include nicotinoyl, isonicotinoyl, thenoyl and furoyl. In the present specification, examples of the "3- to 14-membered non-aromatic heterocyclylcarbonyl group" include morpholinylcarbonyl, piperidinylcarbonyl and pyrrolidinylcarbonyl.

[0035] As used herein, "mono- or di-C 1-6 Examples of the "alkyl-carbamoyl group" include methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl and N-ethyl-N-methylcarbamoyl. As used herein, "mono- or di-C 7-16 Examples of the "aralkyl-carbamoyl group" include benzylcarbamoyl and phenethylcarbamoyl. As used herein, "C 1-6 Examples of the "alkylsulfonyl group" include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, sec-butylsulfonyl and tert-butylsulfonyl. As used herein, "optionally halogenated C 1-6 Examples of the "alkylsulfonyl group" include C alkylsulfonyl groups optionally having 1 to 7, preferably 1 to 5, halogen atoms. 1-6 Specific examples of alkylsulfonyl groups include methylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, 4,4,4-trifluorobutylsulfonyl, pentylsulfonyl, and hexylsulfonyl. As used herein, "C 6-14 Examples of the "arylsulfonyl group" include phenylsulfonyl, 1-naphthylsulfonyl and 2-naphthylsulfonyl.

[0036] As used herein, examples of "substituents" include a halogen atom, a cyano group, a nitro group, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an acyl group, an optionally substituted amino group, an optionally substituted carbamoyl group, an optionally substituted thiocarbamoyl group, an optionally substituted sulfamoyl group, an optionally substituted hydroxy group, an optionally substituted sulfanyl (SH) group, and an optionally substituted silyl group. As used herein, examples of "hydrocarbon groups" (including the "hydrocarbon groups" of "optionally substituted hydrocarbon groups") include C 1-6 Alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkenyl group, C 6-14 Aryl groups and C 7-16 Contains aralkyl groups.

[0037] In this specification, examples of the "optionally substituted hydrocarbon group" include hydrocarbon groups optionally having a substituent selected from the following substituent group A. [Substituent Group A] (1) a halogen atom, (2) a nitro group, (3) a cyano group, (4) an oxo group, (5) a hydroxy group, (6) Optionally halogenated C 1-6 alkoxy groups, (7) C 6-14 aryloxy groups (e.g., phenoxy, naphthoxy); (8) C 7-16 aralkyloxy groups (e.g., benzyloxy), (9) 5- to 14-membered aromatic heterocyclyloxy groups (e.g., pyridyloxy), (10) 3- to 14-membered non-aromatic heterocyclyloxy groups (e.g., morpholinyloxy, piperidinyloxy), (11) C 1-6alkyl-carbonyloxy groups (e.g., acetoxy, propanoyloxy); (12) C 6-14 aryl-carbonyloxy groups (e.g., benzoyloxy, 1-naphthoyloxy, 2-naphthoyloxy); (13) C 1-6 alkoxy-carbonyloxy groups (e.g., methoxycarbonyloxy, ethoxycarbonyloxy, propoxycarbonyloxy, butoxycarbonyloxy); (14) Mono- or di-C 1-6 alkyl-carbamoyloxy groups (e.g., methylcarbamoyloxy, ethylcarbamoyloxy, dimethylcarbamoyloxy, diethylcarbamoyloxy); (15) C 6-14 aryl-carbamoyloxy groups (e.g., phenylcarbamoyloxy, naphthylcarbamoyloxy); (16) 5- to 14-membered aromatic heterocyclylcarbonyloxy groups (e.g., nicotinoyloxy), (17) 3- to 14-membered non-aromatic heterocyclylcarbonyloxy groups (e.g., morpholinylcarbonyloxy, piperidinylcarbonyloxy), (18) Optionally halogenated C 1-6 alkylsulfonyloxy groups (e.g., methylsulfonyloxy, trifluoromethylsulfonyloxy); (19) In some cases C 1-6 C substituted with alkyl group 6-14 arylsulfonyloxy groups (e.g., phenylsulfonyloxy, toluenesulfonyloxy); (20) optionally halogenated C 1-6 alkylthio groups, (21) a 5- to 14-membered aromatic heterocyclic group, (22) a 3- to 14-membered non-aromatic heterocyclic group, (23) formyl group, (24) carboxy group, (25) optionally halogenated C 1-6 alkyl-carbonyl groups, (26) C 6-14 aryl-carbonyl groups, (27) a 5- to 14-membered aromatic heterocyclylcarbonyl group, (28) 3- to 14-membered non-aromatic heterocyclylcarbonyl group, (29) C 1-6 alkoxy-carbonyl groups, (30) C 6-14 aryloxy-carbonyl groups (e.g., phenyloxycarbonyl, 1-naphthyloxycarbonyl, 2-naphthyloxycarbonyl); (31) C 7-16 aralkyloxy-carbonyl groups (e.g., benzyloxycarbonyl, phenethyloxycarbonyl), (32) a carbamoyl group, (33) thiocarbamoyl group, (34) Mono- or di-C 1-6 alkyl-carbamoyl groups, (35) C 6-14 aryl-carbamoyl groups (e.g., phenylcarbamoyl); (36) 5- to 14-membered aromatic heterocyclylcarbamoyl groups (e.g., pyridylcarbamoyl, thienylcarbamoyl), (37) 3- to 14-membered non-aromatic heterocyclylcarbamoyl groups (e.g., morpholinylcarbamoyl, piperidinylcarbamoyl), (38) optionally halogenated C 1-6 alkylsulfonyl groups, (39) C 6-14 arylsulfonyl groups, (40) 5- to 14-membered aromatic heterocyclylsulfonyl groups (e.g., pyridylsulfonyl, thienylsulfonyl), (41) optionally halogenated C 1-6 alkylsulfinyl groups, (42) C 6-14 arylsulfinyl groups (e.g., phenylsulfinyl, 1-naphthylsulfinyl, 2-naphthylsulfinyl); (43) 5- to 14-membered aromatic heterocyclylsulfinyl groups (e.g., pyridylsulfinyl, thienylsulfinyl), (44) amino group, (45) Mono- or di-C 1-6 alkylamino groups (e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, N-ethyl-N-methylamino); (46) Mono- or di-C 6-14 arylamino groups (e.g., phenylamino); (47) 5- to 14-membered aromatic heterocyclylamino groups (e.g., pyridylamino), (48) C 7-16 aralkylamino groups (e.g., benzylamino), (49) formylamino group, (50) C 1-6 alkyl-carbonylamino groups (e.g., acetylamino, propanoylamino, butanoylamino); (51)(C 1-6 Alkyl)(C 1-6 alkyl-carbonyl)amino groups (e.g., N-acetyl-N-methylamino), (52) C 6-14 aryl-carbonylamino groups (e.g., phenylcarbonylamino, naphthylcarbonylamino); (53) C 1-6 alkoxycarbonylamino groups (e.g., methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, butoxycarbonylamino, tert-butoxycarbonylamino), (54) C 7-16 aralkyloxy-carbonylamino groups (e.g., benzyloxycarbonylamino), (55) C 1-6 alkylsulfonylamino groups (e.g., methylsulfonylamino, ethylsulfonylamino); (56) C 6-14 arylsulfonylamino group optionally C 1-6substituted with an alkyl group (e.g., phenylsulfonylamino, toluenesulfonylamino); (57) Optionally halogenated C 1-6 alkyl groups, (58) C 2-6 alkenyl groups, (59) C 2-6 alkynyl groups, (60) C 3-10 cycloalkyl groups, (61) C 3-10 cycloalkenyl groups and (62) C 6-14 Aryl groups.

[0038] The number of the above-mentioned substituents in the "optionally substituted hydrocarbon group" is, for example, 1 to 5, preferably 1 to 3. When the number of substituents exceeds 2, the respective substituents may be the same or different. In this specification, examples of the "heterocyclic group" (including the "heterocyclic group" of the "optionally substituted heterocyclic group") include (i) an aromatic heterocyclic group, (ii) a non-aromatic heterocyclic group, and (iii) a 7- to 10-membered bridged heterocyclic group, each of which contains, in addition to carbon atoms, 1 to 4 heteroatoms selected from a nitrogen atom, a sulfur atom, and an oxygen atom as ring-constituting atoms.

[0039] In this specification, examples of the "aromatic heterocyclic group" (including "5- to 14-membered aromatic heterocyclic group") include 5- to 14-membered (preferably 5- to 10-membered) aromatic heterocyclic groups. Preferred examples of "aromatic heterocyclic groups" include 5- or 6-membered monocyclic aromatic heterocyclic groups, such as thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and the like; and 8- to 14-membered fused polycyclic (preferably bi- or tricyclic) aromatic heterocyclic groups, such as benzothiophenyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, imidazopyridinyl, thienopyridinyl, furopyridinyl, pyrrolopyridinyl, pyrazolopyridinyl, oxazolopyridinyl, thiazolopyridinyl, imidazopyrazinyl, imidazopyrimidinyl, thienopyrimidinyl, furopyrimidinyl phenyl, pyrrolopyrimidinyl, pyrazolopyrimidinyl, oxazolopyrimidinyl, thiazolopyrimidinyl, pyrazolotriazinyl, naphtho[2,3-b]thienyl, phenoxathiinyl, indolyl, isoindolyl, 1H-indazolyl, purinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and the like.

[0040] In this specification, examples of the "non-aromatic heterocyclic group" (including the "3- to 14-membered non-aromatic heterocyclic group") include 3- to 14-membered (preferably 4- to 10-membered) non-aromatic heterocyclic groups containing, in addition to carbon atoms, 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms, and oxygen atoms as ring-constituting atoms. Preferred examples of the "non-aromatic heterocyclic group" include 3- to 8-membered monocyclic non-aromatic heterocyclic groups, such as aziridinyl, oxiranyl, thiiranyl, azetidinyl, oxetanyl, thietanyl, tetrahydrothienyl, tetrahydrofuranyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, oxazolinyl, oxazolidinyl, pyrazolinyl, pyrazolidinyl, thiazolinyl, thiazolidinyl, and tetrahydroisothiazolyl. , tetrahydrooxazolyl, tetrahydroisoxazolyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydropyridinyl, dihydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, azepanyl, diazepanyl, azepinyl, oxepanyl, azocanyl, diazocanyl, and the like; and 9- to 14-membered fused polycyclic (preferably bi- or tricyclic) non-aromatic heterocyclic groups, such as dihydrobenzofuranyl, dihydrobenzimidazolyl, dihydrobenzoxazolyl, dihydrobenzothiazolyl, dihydrobenzisothiazolyl, dihydronaphtho[2,3-b]thienyl, tetrahydroisoquinolyl, tetrahydroquinolyl, 4H-quinolidinyl, indolinyl, isoindolinyl, tetrahydrothieno[2,3-c]pyridinyl, tetrahydrobenzazolyl, tetrahydrobenzo[2,3-c]pyridin ... Examples of tetrahydroquinoxalinyl include tetrahydrophenanthridinyl, hexahydrophenothiazinyl, hexahydrophenoxazinyl, tetrahydrophthalazinyl, tetrahydronaphthyridinyl, tetrahydroquinazolinyl, tetrahydrocinnolinyl, tetrahydrocarbazolyl, tetrahydro-β-carbolinyl, tetrahydroacrydinyl, tetrahydrophenazinyl, tetrahydrothioxanthenyl, octahydroisoquinolyl, and the like.

[0041] In the present specification, preferred examples of the "7- to 10-membered bridged heterocyclic group" include quinuclidinyl and 7-azabicyclo[2.2.1]heptanyl. In this specification, examples of the "nitrogen-containing heterocyclic group" include "heterocyclic groups" that contain at least one nitrogen atom as a ring-constituting atom. In this specification, examples of the "optionally substituted heterocyclic group" include a heterocyclic group optionally having a substituent selected from the above-mentioned substituent group A. The number of substituents in the "optionally substituted heterocyclic group" is, for example, 1 to 3. When the number of substituents exceeds 2, the respective substituents may be the same or different.

[0042] As used herein, examples of "acyl groups" include "C groups each optionally containing a halogen atom, optionally halogenated C groups" and "C groups each optionally containing a halogen atom, optionally halogenated C groups". 1-6 C having 1 to 3 substituents selected from an alkoxy group, a hydroxy group, a nitro group, a cyano group, an amino group, and a carbamoyl group 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 3-10 Cycloalkenyl group, C 6-14 Aryl group, C 7-16 These include a formyl group, a carboxy group, a carbamoyl group, a thiocarbamoyl group, a sulfino group, a sulfo group, a sulfamoyl group, and a phosphono group, each of which has one or two substituents selected from an aralkyl group, a 5- to 14-membered aromatic heterocyclic group, and a 3- to 14-membered non-aromatic heterocyclic group. Examples of "acyl groups" also include hydrocarbon-sulfonyl groups, heterocyclylsulfonyl groups, hydrocarbon-sulfinyl groups, and heterocyclylsulfinyl groups. Here, the term "hydrocarbon-sulfonyl group" refers to a sulfonyl group bonded to a hydrocarbon group, the term "heterocyclylsulfonyl group" refers to a sulfonyl group bonded to a heterocyclic group, the term "hydrocarbon-sulfinyl group" refers to a sulfinyl group bonded to a hydrocarbon group, and the term "heterocyclylsulfinyl group" refers to a sulfinyl group bonded to a heterocyclic group. Preferred examples of the "acyl group" include a formyl group, a carboxy group, and C 1-6 Alkyl-carbonyl group, C 2-6 Alkenyl-carbonyl groups (e.g., crotonoyl), C 3-10Cycloalkyl-carbonyl groups (e.g., cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, cycloheptanecarbonyl), C 3-10 Cycloalkenyl-carbonyl groups (e.g., 2-cyclohexenecarbonyl), C 6-14 Aryl-carbonyl group, C 7-16 Aralkyl-carbonyl group, 5- to 14-membered aromatic heterocyclylcarbonyl group, 3- to 14-membered non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl group, C 6-14 Aryloxy-carbonyl groups (e.g., phenyloxycarbonyl, naphthyloxycarbonyl), C 7-16 Aralkyloxy-carbonyl group (e.g., benzyloxycarbonyl, phenethyloxycarbonyl), carbamoyl group, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 2-6 Alkenyl-carbamoyl groups (e.g., diallylcarbamoyl), mono- or di-C 3-10 Cycloalkyl-carbamoyl groups (e.g., cyclopropylcarbamoyl), mono- or di-C 6-14 Aryl-carbamoyl groups (e.g., phenylcarbamoyl), mono- or di-C 7-16 Aralkyl-carbamoyl group, 5- to 14-membered aromatic heterocyclylcarbamoyl group (e.g., pyridylcarbamoyl), thiocarbamoyl group, mono- or di-C 1-6 Alkyl-thiocarbamoyl groups (e.g., methylthiocarbamoyl, N-ethyl-N-methylthiocarbamoyl), mono- or di-C 2-6 Alkenyl-thiocarbamoyl groups (e.g., diallylthiocarbamoyl), mono- or di-C 3-10 Cycloalkyl-thiocarbamoyl groups (e.g., cyclopropylthiocarbamoyl, cyclohexylthiocarbamoyl), mono- or di-C 6-14 Aryl-thiocarbamoyl groups (e.g., phenylthiocarbamoyl), mono- or di-C 7-16Aralkyl-thiocarbamoyl groups (e.g., benzylthiocarbamoyl, phenethylthiocarbamoyl), 5- to 14-membered aromatic heterocyclylthiocarbamoyl groups (e.g., pyridylthiocarbamoyl), sulfino groups, C 1-6 Alkyl sulfinyl group (e.g., methyl sulfinyl, ethyl sulfinyl), sulfo group, C 1-6 Alkylsulfonyl group, C 6-14 Arylsulfonyl group, phosphono group and mono- or di-C 1-6 It includes alkylphosphono groups (eg, dimethylphosphono, diethylphosphono, diisopropylphosphono, dibutylphosphono).

[0043] In the present specification, examples of the "optionally substituted amino group" include "C 10 optionally having 1 to 3 substituents each optionally selected from the substituent group A". 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl group, C 7-16 Aralkyl group, C 1-6 Alkyl-carbonyl group, C 6-14 Aryl-carbonyl group, C 7-16 Aralkyl-carbonyl group, 5- to 14-membered aromatic heterocyclylcarbonyl group, 3- to 14-membered non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl group, 5- to 14-membered aromatic heterocyclic group, carbamoyl group, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 7-16 Aralkyl-carbamoyl group, C 1-6 Alkylsulfonyl group and C 6-14 arylsulfonyl groups.” Examples of preferred optionally substituted amino groups are amino groups, mono- or di-(optionally halogenated C 1-6 alkyl)amino groups (e.g., methylamino, trifluoromethylamino, dimethylamino, ethylamino, diethylamino, propylamino, dibutylamino), mono- or di-C2-6 Alkenylamino groups (e.g., diallylamino), mono- or di-C 3-10 Cycloalkylamino groups (e.g., cyclopropylamino, cyclohexylamino), mono- or di-C 6-14 Arylamino groups (e.g., phenylamino), mono- or di-C 7-16 Aralkylamino groups (e.g., benzylamino, dibenzylamino), mono- or di-(optionally halogenated C 1-6 alkyl)-carbonylamino group (e.g., acetylamino, propionylamino), mono- or di-C 6-14 Aryl-carbonylamino groups (e.g., benzoylamino), mono- or di-C 7-16 Aralkyl-carbonylamino group (e.g., benzylcarbonylamino), mono- or di-5 to 14-membered aromatic heterocyclylcarbonylamino group (e.g., nicotinoylamino, isonicotinoylamino), mono- or di-3 to 14-membered non-aromatic heterocyclylcarbonylamino group (e.g., piperidinylcarbonylamino), mono- or di-C 1-6 Alkoxy-carbonylamino group (e.g., tert-butoxycarbonylamino), 5- to 14-membered aromatic heterocyclylamino group (e.g., pyridylamino), carbamoylamino group, (mono- or di-C 1-6 alkyl-carbamoyl)amino groups (e.g., methylcarbamoylamino), (mono- or di-C 7-16 aralkyl-carbamoyl)amino group (e.g., benzylcarbamoylamino), C 1-6 Alkyl sulfonylamino groups (e.g., methyl sulfonyl amino, ethyl sulfonyl amino), C 6-14 Arylsulfonylamino groups (e.g., phenylsulfonylamino), (C 1-6 Alkyl)(C 1-6 alkyl-carbonyl)amino groups (e.g., N-acetyl-N-methylamino) and (C 1-6 Alkyl)(C 6-14 aryl-carbonyl)amino groups (e.g., N-benzoyl-N-methylamino).

[0044] In the present specification, examples of the "optionally substituted carbamoyl group" include "C 10 optionally having 1 to 3 substituents each optionally selected from Substituent Group A". 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl group, C 7-16 Aralkyl group, C 1-6 Alkyl-carbonyl group, C 6-14 Aryl-carbonyl group, C 7-16 Aralkyl-carbonyl group, 5- to 14-membered aromatic heterocyclylcarbonyl group, 3- to 14-membered non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl group, 5- to 14-membered aromatic heterocyclic group, carbamoyl group, mono- or di-C 1-6 Alkyl-carbamoyl group and mono- or di-C 7-16 aralkyl-carbamoyl groups”. Examples of preferred optionally substituted carbamoyl groups include carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 2-6 Alkenyl-carbamoyl groups (e.g., diallylcarbamoyl), mono- or di-C 3-10 Cycloalkyl-carbamoyl groups (e.g., cyclopropylcarbamoyl, cyclohexylcarbamoyl), mono- or di-C 6-14 Aryl-carbamoyl groups (e.g., phenylcarbamoyl), mono- or di-C 7-16 Aralkyl-carbamoyl group, mono- or di-C 1-6 Alkyl-carbonyl-carbamoyl groups (e.g., acetylcarbamoyl, propionylcarbamoyl), mono- or di-C 6-14 It includes aryl-carbonyl-carbamoyl groups (eg, benzoylcarbamoyl) and 5- to 14-membered aromatic heterocyclylcarbamoyl groups (eg, pyridylcarbamoyl).

[0045] In the present specification, examples of the "optionally substituted thiocarbamoyl group" include "C thiocarbamoyl groups each optionally having 1 to 3 substituents selected from the substituent group A". 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl group, C 7-16 Aralkyl group, C 1-6 Alkyl-carbonyl group, C 6-14 Aryl-carbonyl group, C 7-16 Aralkyl-carbonyl group, 5- to 14-membered aromatic heterocyclylcarbonyl group, 3- to 14-membered non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl group, 5- to 14-membered aromatic heterocyclic group, carbamoyl group, mono- or di-C 1-6 Alkyl-carbamoyl group and mono- or di-C 7-16 aralkyl-carbamoyl groups and thiocarbamoyl groups having one or two substituents selected from the group consisting of aryl, ... Examples of preferred optionally substituted thiocarbamoyl groups include thiocarbamoyl groups, mono- or di-C 1-6 Alkyl-thiocarbamoyl groups (e.g., methylthiocarbamoyl, ethylthiocarbamoyl, dimethylthiocarbamoyl, diethylthiocarbamoyl, N-ethyl-N-methylthiocarbamoyl), mono- or di-C 2-6 Alkenyl-thiocarbamoyl groups (e.g., diallylthiocarbamoyl), mono- or di-C 3-10 Cycloalkyl-thiocarbamoyl groups (e.g., cyclopropylthiocarbamoyl, cyclohexylthiocarbamoyl), mono- or di-C 6-14 Aryl-thiocarbamoyl groups (e.g., phenylthiocarbamoyl), mono- or di-C 7-16 Aralkyl-thiocarbamoyl groups (e.g., benzylthiocarbamoyl, phenethylthiocarbamoyl), mono- or di-C 1-6 Alkyl-carbonyl-thiocarbamoyl groups (e.g., acetylthiocarbamoyl, propionylthiocarbamoyl), mono- or di-C 6-14They include aryl-carbonyl-thiocarbamoyl groups (eg, benzoylthiocarbamoyl) and 5- to 14-membered aromatic heterocyclylthiocarbamoyl groups (eg, pyridylthiocarbamoyl).

[0046] In the present specification, examples of the "optionally substituted sulfamoyl group" include "C 10 optionally having 1 to 3 substituents each optionally selected from Substituent Group A". 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl group, C 7-16 Aralkyl group, C 1-6 Alkyl-carbonyl group, C 6-14 Aryl-carbonyl group, C 7-16 Aralkyl-carbonyl group, 5- to 14-membered aromatic heterocyclylcarbonyl group, 3- to 14-membered non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl group, 5- to 14-membered aromatic heterocyclic group, carbamoyl group, mono- or di-C 1-6 Alkyl-carbamoyl group and mono- or di-C 7-16 and sulfamoyl groups having one or two substituents selected from aralkyl-carbamoyl groups. Examples of preferred optionally substituted sulfamoyl groups include sulfamoyl groups, mono- or di-C 1-6 Alkyl-sulfamoyl groups (e.g., methylsulfamoyl, ethylsulfamoyl, dimethylsulfamoyl, diethylsulfamoyl, N-ethyl-N-methylsulfamoyl), mono- or di-C 2-6 Alkenyl-sulfamoyl groups (e.g., diallylsulfamoyl), mono- or di-C 3-10 Cycloalkyl-sulfamoyl groups (e.g., cyclopropylsulfamoyl, cyclohexylsulfamoyl), mono- or di-C 6-14 Aryl-sulfamoyl groups (e.g., phenylsulfamoyl), mono- or di-C 7-16 Aralkyl-sulfamoyl group (e.g., benzylsulfamoyl, phenethylsulfamoyl), mono- or di-C1-6 Alkyl-carbonyl-sulfamoyl group (e.g., acetylsulfamoyl, propionylsulfamoyl), mono- or di-C 6-14 They include aryl-carbonyl-sulfamoyl groups (eg, benzoylsulfamoyl) and 5- to 14-membered aromatic heterocyclylsulfamoyl groups (eg, pyridylsulfamoyl).

[0047] In this specification, examples of the "optionally substituted hydroxy group" include "C 10 optionally having 1 to 3 substituents each optionally selected from the substituent group A". 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl group, C 7-16 Aralkyl group, C 1-6 Alkyl-carbonyl group, C 6-14 Aryl-carbonyl group, C 7-16 Aralkyl-carbonyl group, 5- to 14-membered aromatic heterocyclylcarbonyl group, 3- to 14-membered non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl group, 5- to 14-membered aromatic heterocyclic group, carbamoyl group, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 7-16 Aralkyl-carbamoyl group, C 1-6 Alkylsulfonyl group and C 6-14 arylsulfonyl groups. Examples of preferred optionally substituted hydroxy groups include hydroxy groups, C 1-6 Alkoxy group, C 2-6 Alkenyloxy groups (e.g., allyloxy, 2-butenyloxy, 2-pentenyloxy, 3-hexenyloxy), C 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), C 6-14 Aryloxy groups (e.g., phenoxy, naphthyloxy), C 7-16 Aralkyloxy groups (e.g., benzyloxy, phenethyloxy), C 1-6Alkyl-carbonyloxy groups (e.g., acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pivaloyloxy), C 6-14 Aryl-carbonyloxy groups (e.g., benzoyloxy), C 7-16 Aralkyl-carbonyloxy groups (e.g., benzylcarbonyloxy), 5- to 14-membered aromatic heterocyclylcarbonyloxy groups (e.g., nicotinoyloxy), 3- to 14-membered non-aromatic heterocyclylcarbonyloxy groups (e.g., piperidinylcarbonyloxy), C 1-6 Alkoxy-carbonyloxy groups (e.g., tert-butoxycarbonyloxy), 5- to 14-membered aromatic heterocyclyloxy groups (e.g., pyridyloxy), carbamoyloxy groups, C 1-6 Alkyl-carbamoyloxy groups (e.g., methylcarbamoyloxy), C 7-16 Aralkyl-carbamoyloxy groups (e.g., benzylcarbamoyloxy), C 1-6 Alkyl sulfonyloxy groups (e.g., methyl sulfonyloxy, ethyl sulfonyloxy) and C 6-14 Arylsulfonyloxy groups (eg, phenylsulfonyloxy) are included.

[0048] In the present specification, examples of the "optionally substituted sulfanyl group" include "C 10 optionally having 1 to 3 substituents each optionally selected from the substituent group A". 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl group, C 7-16 Aralkyl group, C 1-6 Alkyl-carbonyl group, C 6-14 and a sulfanyl group having one substituent selected from an aryl-carbonyl group and a 5- to 14-membered aromatic heterocyclic group, and a halogenated sulfanyl group. Examples of preferred optionally substituted sulfanyl groups include sulfanyl (—SH) groups, C 1-6 Alkylthio group, C 2-6Alkenylthio groups (e.g., allylthio, 2-butenylthio, 2-pentenylthio, 3-hexenylthio), C 3-10 cycloalkylthio groups (e.g., cyclohexylthio), C 6-14 Arylthio groups (e.g., phenylthio, naphthylthio), C 7-16 Aralkylthio groups (e.g., benzylthio, phenethylthio), C 1-6 Alkyl-carbonylthio groups (e.g., acetylthio, propionylthio, butyrylthio, isobutyrylthio, pivaloylthio), C 6-14 These include aryl-carbonylthio groups (eg, benzoylthio), 5- to 14-membered aromatic heterocyclylthio groups (eg, pyridylthio), and halogenated thio groups (eg, pentafluorothio).

[0049] In the present specification, examples of the "optionally substituted silyl group" include "C silyl groups each having 1 to 3 substituents optionally selected from the substituent group A". 1-6 Alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl groups and C 7-16 The term "silyl group" includes a silyl group having 1 to 3 substituents selected from aralkyl groups. An example of a preferred optionally substituted silyl group is tri-C 1-6 Includes alkylsilyl groups (eg, trimethylsilyl, tert-butyl(dimethyl)silyl).

[0050] As used herein, examples of "hydrocarbon rings" include C 6-14 Aromatic hydrocarbon ring, C 3-10 Cycloalkanes and C 3-10 Contains cycloalkenes. As used herein, "C 6-14 Examples of the "aromatic hydrocarbon ring" include benzene and naphthalene. As used herein, "C 3-10 Examples of "cycloalkanes" include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, and cyclooctane. As used herein, "C 3-10 Examples of "cycloalkenes" include cyclopropene, cyclobutene, cyclopentene, cyclohexene, cycloheptene, and cyclooctene. In this specification, examples of the "heterocycle" include aromatic heterocycles and non-aromatic heterocycles, each of which contains, in addition to carbon atoms, 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms, and oxygen atoms as ring-constituting atoms.

[0051] In this specification, examples of "aromatic heterocycles" include 5- to 14-membered (preferably 5- to 10-membered) aromatic heterocycles containing, in addition to carbon atoms, 1 to 4 heteroatoms selected from nitrogen, sulfur, and oxygen atoms as ring-constituting atoms. Preferred examples of "aromatic heterocycles" include 5- or 6-membered monocyclic aromatic heterocycles, such as thiophene, furan, pyrrole, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, 1,2,4-oxadiazole, 1,3,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole, triazole, tetrazole, and triazine; and 8- to 14-membered fused polycyclic (preferably bicyclic or tricyclic) aromatic heterocycles, such as benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzotriazole, imidazopyridine, thienopyridine, furopyridine, pyrrolopyridine, pyrazolopyridine, oxazolopyridine, thiazolopyridine, imidazopyrazine, imidazopyrimidine, thienopyrimidine, furopyrimidine, pyrrolo These include pyrimidine, pyrazolopyrimidine, oxazolopyrimidine, thiazolopyrimidine, pyrazolopyrimidine, pyrazolotriazine, naphtho[2,3-b]thiophene, phenoxathiin, indole, isoindole, 1H-indazole, purine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, carbazole, β-carboline, phenanthridine, acridine, phenazine, phenothiazine, phenoxazine, and the like.

[0052] In this specification, examples of the "non-aromatic heterocycle" include 3- to 14-membered (preferably 4- to 10-membered) non-aromatic heterocycles containing, in addition to carbon atoms, 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms, and oxygen atoms as ring-constituting atoms. Preferred examples of the "non-aromatic heterocycle" include 3- to 8-membered monocyclic non-aromatic heterocycles, such as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, tetrahydrothiophene, tetrahydrofuran, pyrroline, pyrrolidine, imidazoline, imidazolidine, oxazoline, oxazolidine, pyrazoline, pyrazolidine, thiazoline, thiazolidine, tetrahydroisothiazole, tetrahydrooxazole, tetrahydroisoxazole, piperidine, piperazine, tetrahydropyridine, dihydropyridine, dihydrothiopyran, tetrahydropyrimidine, tetrahydropyridazine, dihydropyran, tetrahydropyran, tetrahydrothiopyran, morpholine, thiomorpholine, azepane, diazepane, azepine, azocane, diazocane, oxepane, and the like; and 9- to 14-membered fused polycyclic (preferably bi- or tricyclic) non-aromatic heterocycles, such as dihydrobenzofuran, dihydrobenzimidazole, dihydrobenzoxazole, dihydrobenzothiazole, dihydrobenzisothiazole, dihydronaphtho[2,3-b]thiophene, tetrahydroisoquinoline, tetrahydroquinoline, 4H-quinolizine, indoline, isoindoline, tetrahydrothieno[2,3-c]pyridine, tetrahydrobenzazepine, tetrahydroquinoxaline, tetrahydrophenanthridine, hexahydrophenothiazine, hexahydrophenoxazine, tetrahydrophthalazine, tetrahydronaphthyridine, tetrahydroquinazoline, tetrahydrocinnoline, tetrahydrocarbazole, tetrahydro-β-carboline, tetrahydroacridine, tetrahydrophenazine, tetrahydrothioxanthene, octahydroisoquinoline, and the like. In this specification, examples of "nitrogen-containing heterocycle" include "heterocycles" containing at least one nitrogen atom as a ring-constituting atom. As used herein, "C 6-14Examples of "aromatic hydrocarbon ring" are those listed above under "C 6-14 Examples of "aromatic hydrocarbon rings" include anthracene, phenanthrene, and acenaphthylene.

[0053] The definition of each symbol in formula (I) is explained in detail below.

[0054] X 1 is N or CR X1 where R X1 is a hydrogen atom, a halogen atom (e.g., a fluorine atom) or C 1-6 It is an alkyl group (eg, methyl). X 1 is preferably CH.

[0055] X 2 , X 3 and X 4 are each independently C or N, and X 2 , X 3 and X 4 One of them is N and the other two are C.

[0056] X 5 is N or CR X5 where R X5 is a hydrogen atom. X 5 is preferably N.

[0057] X 6 is N or CR X6 where R X6 is a hydrogen atom. X 6 is preferably CH.

[0058] formula: [ka] is in particular a moiety of formula (Ia), (Ib) or (Ic): [ka] (wherein each symbol is as defined above.) It is expressed by:

[0059] formula [ka] is preferably represented by formula (Ia1), (Ib1), (Ic1), (Ia2), (Ib2) or (Ic2): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by: In this embodiment, X 1 is N or CR X1 where R X1 is a hydrogen atom, a halogen atom (e.g., a fluorine atom) or C 1-6 An alkyl group (eg, methyl), preferably CH. In this embodiment, R X5 is a hydrogen atom. In this embodiment, R X6 is a hydrogen atom.

[0060] formula [ka] The moiety represented by formula (Ia1), (Ib1), (Ic1) or (Ib2) is more preferably represented by formula (Ia1), (Ib1), (Ic1) or (Ib2): [ka] (wherein each symbol is as defined above.) is a substructure represented by Even more preferably, the formula (Ia1), (Ib1) or (Ic1): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by:

[0061] formula [ka] is even more preferably represented by formula (IIa), (IIb) or (IIc): [ka] (wherein each symbol is as defined above.) is a substructure represented by and in particular of formula (IIa1), (IIb1), (IIc1), (IIa2), (IIb2) or (IIc2): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by: In this embodiment, R X1 is a hydrogen atom, a halogen atom (e.g., a fluorine atom) or C 1-6 An alkyl group (eg, methyl), preferably a hydrogen atom.

[0062] formula [ka] is even more preferably represented by formula (IIa1), (IIb1), (IIc1) or (IIb2): [ka] (wherein each symbol is as defined above.) is a substructure represented by Even more preferably, the formula (IIa1), (IIb1) or (IIc1): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by:

[0063] formula [ka] is particularly preferably represented by formula (IIIa), (IIIb) or (IIIc): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by:

[0064] Y 1 is N or CR Y1 where R Y1 is a hydrogen atom. Y 1 is preferably CH.

[0065] Y 2 is N or CR Y2 where R Y2 is a hydrogen atom, a halogen atom (for example, a fluorine atom, a chlorine atom) or a cyano group. Y 2 is preferably N or CR Y2 where R Y2 is a hydrogen atom or a halogen atom (for example, a fluorine atom, a chlorine atom), more preferably CH or CF, particularly preferably CF.

[0066] Y 3 is N or CR Y3 where R Y3 is a hydrogen atom or a halogen atom (for example, a fluorine atom). Y 3 is preferably CH.

[0067] Y 4 is N or CR Y4 where R Y4 is a hydrogen atom or a halogen atom (for example, a fluorine atom). Y 4is preferably CH.

[0068] formula [ka] The partial structure represented by the formulas (Ar-1) to (Ar-12): [ka] (wherein each symbol is as defined above.) It is expressed by: Y 1 , Y 2 , Y 3 and Y 4 are all C, the partial structure is represented by formula (Ar-1). Y 1 , Y 2 , Y 3 and Y 4 If at least one of the groups is N, the partial structure is represented by formulas (Ar-2) to (Ar-12). These partial structures are collectively represented by the formula: [ka] [During the ceremony, Y 1a is N or CR Y1a where R Y1a is a hydrogen atom; Y 2a is N or CR Y2a where R Y2a is a hydrogen atom or a halogen atom (e.g., a fluorine atom); Y 3a is N or CR Y3a where R Y3a is a hydrogen atom; Y 4a is N or CR Y4a where R Y4a is a hydrogen atom; and Y 1a , Y 2a , Y 3a and Y 4a At least one of the is N. It is expressed by: Y 1a is preferably N. Y 2a is preferably CH. Y 3a is preferably CH. Y 4a is preferably CH.

[0069] formula [ka] The partial structure represented by the formula (Ar-1) to (Ar-11): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by: In this embodiment, R Y1 is a hydrogen atom. In this embodiment, R Y2 is a hydrogen atom, a halogen atom (for example, a fluorine atom, a chlorine atom) or a cyano group, preferably a hydrogen atom or a halogen atom (for example, a fluorine atom, a chlorine atom), more preferably a hydrogen atom or a fluorine atom, and particularly preferably a fluorine atom. In this embodiment, R Y3 is a hydrogen atom or a halogen atom (for example, a fluorine atom), preferably a hydrogen atom. In this embodiment, R Y4 is a hydrogen atom or a halogen atom (for example, a fluorine atom), preferably a hydrogen atom.

[0070] formula [ka] The partial structure represented by formula (Ar-1) or (Ar-2): [ka] (wherein each symbol is as defined above.) is a substructure represented by Even more preferably, the formula (Ar-1-1) or (Ar-2-1): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by: In this embodiment, R Y2 is a hydrogen atom, a halogen atom (for example, a fluorine atom, a chlorine atom) or a cyano group, preferably a hydrogen atom or a halogen atom (for example, a fluorine atom, a chlorine atom), more preferably a hydrogen atom or a fluorine atom, and particularly preferably a fluorine atom.

[0071] formula [ka] The partial structure represented by the formula (Ar-1-1): [ka] (wherein each symbol is as defined above.) It is a partial structure represented by: In this embodiment, R Y2 is a hydrogen atom, a halogen atom (for example, a fluorine atom, a chlorine atom) or a cyano group, preferably a hydrogen atom or a halogen atom (for example, a fluorine atom, a chlorine atom), more preferably a halogen atom (for example, a fluorine atom, a chlorine atom), and particularly preferably a fluorine atom.

[0072] Ring A 1 is optionally further substituted C 6-14 An aromatic hydrocarbon, an optionally further substituted aromatic heterocycle, or an optionally further substituted non-aromatic heterocycle, each of which is optionally fused to an optionally substituted 5- or 6-membered ring.

[0073] "Optionally further substituted C 6-14 Aromatic hydrocarbons" "C 6-14 The "aromatic hydrocarbon" is preferably a benzene ring. The "aromatic heterocycle" of the "optionally further substituted aromatic heterocycle" is preferably a 5- or 6-membered aromatic heterocycle. The "non-aromatic heterocycle" of the "optionally further substituted non-aromatic heterocycle" is preferably a 5- or 6-membered non-aromatic heterocycle.

[0074] Examples of the "5-membered or 6-membered ring" in the "optionally substituted 5-membered or 6-membered ring" are a benzene ring, C 5-6 Includes cycloalkenes, 5- or 6-membered aromatic heterocycles and 5- or 6-membered non-aromatic heterocycles.

[0075] "Optionally further substituted C 6-14 Aromatic hydrocarbons" "C 6-14 The "aromatic heterocycle" in the "aromatic hydrocarbon" and "optionally further substituted aromatic heterocycle", the "non-aromatic heterocycle" in the "optionally further substituted non-aromatic heterocycle" and the "5- or 6-membered ring" in the "optionally substituted 5- or 6-membered ring" are represented by the formula: [ka] In addition to the partial structure represented by the following formula, optionally, it has 1 to 5 (preferably 1 to 3) substituents at appropriate positions.

[0076] Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds two, the respective substituents may be the same or different. Furthermore, the above-mentioned Substituent Group A is optionally substituted with a substituent selected from the Substituent Group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, the respective substituents may be the same or different.

[0077] Ring A 1 is preferably ring A 2, i.e., an optionally further substituted benzene ring, an optionally further substituted 5- or 6-membered aromatic heterocycle, or an optionally further substituted 5- or 6-membered non-aromatic heterocycle, each of which is optionally fused to an optionally substituted 5- or 6-membered ring.

[0078] The "5- or 6-membered aromatic heterocycle" of the "optionally further substituted 5- or 6-membered aromatic heterocycle" is preferably a pyridine ring (optionally oxidized), a pyrimidine ring, a pyridazine ring, a pyrazine ring, a pyrazole ring, a thiazole ring, an imidazole ring, a thiophene ring, or a furan ring. The "5- or 6-membered non-aromatic heterocycle" in the "optionally further substituted 5- or 6-membered non-aromatic heterocycle" is preferably a dihydropyridine ring or a dihydropyrimidine ring.

[0079] Examples of the "5-membered or 6-membered ring" in the "optionally substituted 5-membered or 6-membered ring" are a benzene ring, C 5-6 Includes cycloalkenes, 5- or 6-membered aromatic heterocycles and 5- or 6-membered non-aromatic heterocycles.

[0080] The "benzene ring" of the "optionally further substituted benzene ring", the "5-membered or 6-membered aromatic heterocycle" of the "optionally further substituted 5-membered or 6-membered aromatic heterocycle", the "5-membered or 6-membered non-aromatic heterocycle" of the "optionally further substituted 5-membered or 6-membered non-aromatic heterocycle" and the "5-membered or 6-membered ring" of the "optionally substituted 5-membered or 6-membered ring" are represented by the formula: [ka] In addition to the partial structure represented by the following formula, optionally, it has 1 to 5 (preferably 1 to 3) substituents at appropriate positions.

[0081] Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds two, the respective substituents may be the same or different. Furthermore, the above-mentioned Substituent Group A is optionally substituted with a substituent selected from the Substituent Group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, the respective substituents may be the same or different.

[0082] Ring A 2 is preferably (1) Benzene ring [optionally fused with a 5- to 6-membered monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the fused ring is dihydrobenzofuran, isoindoline), and optionally substituted with 1 to 3 substituents selected from (a) and (b), (a) an oxo group and (b) 1 to 3 Cs, if necessary 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Optionally, further substituted with 1 to 5 substituents selected from (a) to (aa) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms); (c) a hydroxy group, (d) a carboxy group, (e) a formyl group, (f) amino group, (g) a carbamoyl group, (h) C optionally substituted with 1 to 3 substituents selected from (i) to (v) 1-6 Alkyl groups (e.g., methyl, ethyl, isopropyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a hydroxy group, (iii) C 1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6alkylamino groups (e.g., N,N-dimethylamino) and (v) Ji-C 1-6 Alkyl sulfinylidene amino group (e.g., N-dimethyl sulfinylidene amino) (I C 2-6 alkenyl groups (e.g., vinyl), (j) C 2-6 alkynyl groups (e.g., ethynyl), (k) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 Alkylamino groups (e.g., N,N-dimethylamino) (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (l) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (m) C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (o) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino); (p) mono- or di-C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-butylcarbamoyl, N-isobutylcarbamoyl, N-isopentylcarbamoyl, N-neopentylcarbamoyl) (i) a hydroxy group, (ii) C 1-6 alkoxy groups (e.g., methoxy), (iii) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino, N,N-diethylamino); (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (v) Mono- or di-C 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-diethylcarbamoyl); (vi) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclohexyl); (vii) C 6-14 aryl groups (e.g., phenyl); (viii) 5- or 6-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (III) (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxidethiomorpholinyl, tetrahydropyranyl). (I) a hydroxy group, (II) oxo group and (III) C 1-6 Alkyl groups (e.g., methyl) (q) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (r) C optionally substituted with 1 to 3 substituents selected from (i) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy) (i) 1 to 3 Cs, if necessary 1-6 a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl); (s) C 3-10 cycloalkylsulfonyl-carbamoyl groups (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 aryl-carbamoyl groups (e.g., phenylcarbamoyl); (u) 1 to 3 Cs, if necessary 1-6 a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl, piperazinyl) substituted with an alkyl-carbonyl group (e.g., acetyl); (v) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (w) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl, piperidylcarbonyl, morpholinylcarbonyl) optionally substituted with 1 to 3 substituents selected from (i) to (v). (i) a hydroxy group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino) and (v) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (x) a 9- to 14-membered bicyclic non-aromatic heterocyclylcarbonyl group (e.g., tetrahydroimidazopyrazinylcarbonyltetrahydrotriazolopyrazinylcarbonyl), (y) 1 to 3 Cs, if necessary 1-6 5- or 6-membered monocyclic aromatic heterocyclylcarbamoyl groups (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl) substituted with an alkyl group (e.g., methyl); (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group optionally substituted with 1 to 3 substituents selected from (i) to (iv) (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl). (i) an oxo group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 Alkyl-carbonyl groups (e.g., acetyl) and (iv) C 7-16 aralkyl groups (e.g., benzyl) and (aa) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 5- or 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (n) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a carboxy group, (d) amino groups, (e) a carbamoyl group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (vii) 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a hydroxy group, (iv) a carboxy group, (v) C 1-6 alkoxy groups (e.g., methoxy), (vi) C 7-16 aralkyloxy-carbonyl groups (e.g., benzyloxycarbonyl), (vii) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-ethylcarbamoyl, N-propylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) and (viii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (iv) 1-6Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) C 1-6 alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (h) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (I C 1-6 alkyl-carbonyl groups (e.g., acetyl); (j) 1 to 3 Cs, as the case may be 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl), (k) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (l) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) Mono- or di-C 1-6 Alkylamino groups (e.g., N,N-diethylamino) (m) Mono- or Di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (n) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) 5- or 6-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) [optionally further substituted with 1 to 4 substituents selected from (a) to (d)] (a) an oxo group, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C optionally substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) a halogen atom (e.g., a fluorine atom), (II) cyano group and (III) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) is.

[0083] In other embodiments, ring A 2 is preferably (1) Benzene ring [optionally fused with a 5- to 6-membered monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the fused ring is dihydrobenzofuran, isoindoline), and optionally substituted with 1 to 3 substituents selected from (a) and (b)] (a) an oxo group and (b) 1 to 3 Cs, if necessary 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Optionally, further substituted with 1 to 5 substituents selected from (a) to (aa) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms); (c) a hydroxy group, (d) a carboxy group, (e) a formyl group, (f) amino group, (g) a carbamoyl group, (h) C optionally substituted with 1 to 3 substituents selected from (i) to (iv): 1-6 Alkyl groups (e.g., methyl, ethyl, isopropyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a hydroxy group, (iii) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino) and (iv) Di-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (I C 2-6 alkenyl groups (e.g., vinyl), (j) C 2-6 alkynyl groups (e.g., ethynyl), (k) C optionally substituted with 1 to 3 substituents selected from (i) to (ix) 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (l) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (m) C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (o) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino); (p) mono- or di-C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-butylcarbamoyl, N-isobutylcarbamoyl, N-isopentylcarbamoyl, N-neopentylcarbamoyl) (i) a hydroxy group, (ii) C 1-6 alkoxy groups (e.g., methoxy), (iii) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino, N,N-diethylamino); (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (v) Mono- or di-C 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-diethylcarbamoyl); (vi) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclohexyl); (vii) C 6-14 aryl groups (e.g., phenyl); (viii) 5- or 6-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (III) (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxidethiomorpholinyl, tetrahydropyranyl). (I) a hydroxy group, (II) oxo group and (III) C 1-6 Alkyl groups (e.g., methyl) (q) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (r) C optionally substituted with 1 to 3 substituents selected from (i) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy) (i) 1 to 3 Cs, if necessary 1-6 3-8 membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with alkyl group (e.g., methyl) (s) C 3-10 cycloalkylsulfonyl-carbamoyl groups (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 aryl-carbamoyl groups (e.g., phenylcarbamoyl); (u) 1 to 3 Cs, if necessary 1-6a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl, piperazinyl) substituted with an alkyl-carbonyl group (e.g., acetyl); (v) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (w) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl, piperidylcarbonyl, morpholinylcarbonyl) optionally substituted with 1 to 3 substituents selected from (i) to (v). (i) a hydroxy group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino) and (v) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (x) a 9- to 14-membered bicyclic non-aromatic heterocyclylcarbonyl group (e.g., tetrahydroimidazopyrazinylcarbonyltetrahydrotriazolopyrazinylcarbonyl), (y) 1 to 3 Cs, if necessary 1-6 5- or 6-membered monocyclic aromatic heterocyclylcarbamoyl groups (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl) substituted with an alkyl group (e.g., methyl); (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group optionally substituted with 1 to 3 substituents selected from (i) to (iv) (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl). (i) an oxo group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 Alkyl-carbonyl groups (e.g., acetyl) and (iv) C 7-16aralkyl groups (e.g., benzyl) and (aa) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 5- or 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (n) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a carboxy group, (d) amino groups, (e) a carbamoyl group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (viii) 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a hydroxy group, (iv) a carboxy group, (v) C 1-6 alkoxy groups (e.g., methoxy), (vi) C 7-16 aralkyloxy-carbonyl groups (e.g., benzyloxycarbonyl), (vii) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-ethylcarbamoyl, N-propylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) and (viii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (iv) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) C 1-6 alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (h) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (I C 1-6 alkyl-carbonyl groups (e.g., acetyl); (j) 1 to 3 Cs, as the case may be 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl), (k) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (l) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) Mono- or di-C 1-6 Alkylamino groups (e.g., N,N-diethylamino) (m) Mono- or Di-C 1-6Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (n) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) 5- or 6-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) [optionally further substituted with 1 to 4 substituents selected from (a) to (d)] (a) an oxo group, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C optionally substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) a halogen atom (e.g., a fluorine atom), (II) cyano group and (III) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) is.

[0084] In other embodiments, ring A 2 is preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (d). (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (d) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6alkoxy groups (e.g., methoxy), (2) A 5- or 6-membered aromatic heterocycle optionally substituted with 1 to 4 substituents selected from (a) to (c) (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan). (a) a cyano group, (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkyl groups (e.g., methyl) and (c) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) or (3) A 5- or 6-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) optionally further substituted with 1 to 4 substituents selected from (a) to (c). (a) an oxo group, (b) a cyano group and (c) C 1-6 Alkyl groups (e.g., methyl) is.

[0085] Ring A 2 is more preferably (1) Benzene ring [optionally fused with a 5- to 6-membered monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the fused ring is dihydrobenzofuran, isoindoline), and optionally substituted with 1 to 3 substituents selected from (a) and (b)] (a) an oxo group and (b) 1 to 3 Cs, if necessary 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Optionally, further substituted with 1 to 5 substituents selected from (a) to (aa) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms); (c) a hydroxy group, (d) a carboxy group, (e) a formyl group, (f) amino group, (g) a carbamoyl group, (h) C optionally substituted with 1 to 3 substituents selected from (i) to (v) 1-6 Alkyl groups (e.g., methyl, ethyl, isopropyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a hydroxy group, (iii) C 1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino) and (v) Ji-C 1-6 Alkyl sulfinylidene amino group (e.g., N-dimethyl sulfinylidene amino) (I C 2-6 alkenyl groups (e.g., vinyl), (j) C 2-6 alkynyl groups (e.g., ethynyl), (k) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (l) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (m) C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (o) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino); (p) mono- or di-C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-butylcarbamoyl, N-isobutylcarbamoyl, N-isopentylcarbamoyl, N-neopentylcarbamoyl) (i) a hydroxy group, (ii) C 1-6 alkoxy groups (e.g., methoxy), (iii) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino, N,N-diethylamino); (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (v) Mono- or di-C 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-diethylcarbamoyl); (vi) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclohexyl); (vii) C 6-14 aryl groups (e.g., phenyl); (viii) 5- or 6-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (III) (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxidethiomorpholinyl, tetrahydropyranyl). (I) a hydroxy group, (II) oxo group and (III) C 1-6 Alkyl groups (e.g., methyl) (q) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (r) C optionally substituted with 1 to 3 substituents selected from (i) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy) (i) 1 to 3 Cs, if necessary 1-6 3-8 membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with alkyl group (e.g., methyl) (s) C 3-10cycloalkylsulfonyl-carbamoyl groups (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 aryl-carbamoyl groups (e.g., phenylcarbamoyl); (u) 1 to 3 Cs, if necessary 1-6 a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl, piperazinyl) substituted with an alkyl-carbonyl group (e.g., acetyl); (v) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (w) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl, piperidylcarbonyl, morpholinylcarbonyl) optionally substituted with 1 to 3 substituents selected from (i) to (v). (i) a hydroxy group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino) and (v) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (x) a 9- to 14-membered bicyclic non-aromatic heterocyclylcarbonyl group (e.g., tetrahydroimidazopyrazinylcarbonyltetrahydrotriazolopyrazinylcarbonyl), (y) 1 to 3 Cs, if necessary 1-6 5- or 6-membered monocyclic aromatic heterocyclylcarbamoyl groups (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl) substituted with an alkyl group (e.g., methyl); (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group optionally substituted with 1 to 3 substituents selected from (i) to (iv) (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl). (i) an oxo group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 Alkyl-carbonyl groups (e.g., acetyl) and (iv) C 7-16 aralkyl groups (e.g., benzyl) and (aa) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) Pyridine ring (optionally oxidized) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (m) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) an amino group, (d) a carbamoyl group, (e) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (f) C optionally substituted with 1 to 3 substituents selected from (i) to (iv) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) C 1-6 alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (g) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl), (j) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (k) optionally 1 to 3 mono- or di-C 1-6 Mono- or di-C substituted with alkylamino groups (e.g., N,N-diethylamino) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N-ethylcarbamoyl); (l) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (m) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring optionally further substituted with 1 to 3 substituents selected from (a) to (d): (a) a cyano group, (b) an amino group, (c) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) and (d) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (4) a pyridazine ring optionally further substituted with 1 to 3 cyano groups; (5) A pyrazine ring optionally further substituted with 1 to 3 substituents selected from (a) to (c): (a) a cyano group, (b) C 1-6 alkyl groups (e.g., methyl) and (c) C 1-6 alkoxy groups (e.g., methoxy), (6) A pyrazole ring optionally further substituted with 1 to 3 substituents selected from (a) to (c): (a) a cyano group, (b) a carboxy group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (viii) 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a hydroxy group, (iv) a carboxy group, (v) C 1-6 alkoxy groups (e.g., methoxy), (vi) C 7-16 aralkyloxy-carbonyl groups (e.g., benzyloxycarbonyl), (vii) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-ethylcarbamoyl, N-propylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) and (viii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (d) 1 to 3 Cs, as the case may be 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkoxy-carbonyl groups (e.g., propoxycarbonyl, tert-butoxycarbonyl) and (e) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (7) An imidazole ring optionally further substituted with 1 to 3 substituents selected from (a) and (b). (a) a cyano group and (b) C 1-6 alkyl groups (e.g., methyl); (8) One or two more C's, if necessary. 1-6 a thiazole ring substituted with an alkyl group (e.g., methyl); (9) A thiophene ring optionally further substituted with 1 to 3 substituents selected from (a) to (d). (a) a cyano group, (b) a carboxy group, (c) C 1-6 Alkoxy-carbonyl groups (e.g., methoxycarbonyl) and (d) Mono- or di-C 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl); (10) Furan ring, (11) A dihydropyridine ring optionally further substituted with 1 to 4 substituents selected from (a) to (d): (a) a cyano group, (b) an oxo group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C optionally substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) a halogen atom (e.g., a fluorine atom), (II) cyano group and (III) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy, ethoxy) or (12) A dihydropyrimidine ring optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) a cyano group and (b) oxo group is.

[0086] In other embodiments, ring A 2 is more preferably (1) Benzene ring [optionally fused with a 5- to 6-membered monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the fused ring is dihydrobenzofuran, isoindoline), and optionally substituted with 1 to 3 substituents selected from (a) and (b)] (a) an oxo group and (b) 1 to 3 Cs, if necessary 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Optionally, further substituted with 1 to 5 substituents selected from (a) to (aa) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms); (c) a hydroxy group, (d) a carboxy group, (e) a formyl group, (f) amino group, (g) a carbamoyl group, (h) C optionally substituted with 1 to 3 substituents selected from (i) to (iv): 1-6 Alkyl groups (e.g., methyl, ethyl, isopropyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a hydroxy group, (iii) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino) and (iv) Di-C 1-6 Alkyl sulfinylidene amino group (e.g., N-dimethyl sulfinylidene amino) (I C 2-6 alkenyl groups (e.g., vinyl), (j) C 2-6 alkynyl groups (e.g., ethynyl), (k) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (l) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (m) C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) 1 to 3 Cs, as the case may be1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (o) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino); (p) mono- or di-C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-butylcarbamoyl, N-isobutylcarbamoyl, N-isopentylcarbamoyl, N-neopentylcarbamoyl) (i) a hydroxy group, (ii) C 1-6 alkoxy groups (e.g., methoxy), (iii) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino, N,N-diethylamino); (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (v) Mono- or di-C 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-diethylcarbamoyl); (vi) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclohexyl); (vii) C 6-14 aryl groups (e.g., phenyl); (viii) 5- or 6-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (III) (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxidethiomorpholinyl, tetrahydropyranyl). (I) a hydroxy group, (II) oxo group and (III) C 1-6 Alkyl groups (e.g., methyl) (q) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (r) C optionally substituted with 1 to 3 substituents selected from (i) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy) (i) 1 to 3 Cs, if necessary 1-6 3-8 membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with alkyl group (e.g., methyl) (s) C 3-10 cycloalkylsulfonyl-carbamoyl groups (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 aryl-carbamoyl groups (e.g., phenylcarbamoyl); (u) 1 to 3 Cs, if necessary 1-6 a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl, piperazinyl) substituted with an alkyl-carbonyl group (e.g., acetyl); (v) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (w) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl, piperidylcarbonyl, morpholinylcarbonyl) optionally substituted with 1 to 3 substituents selected from (i) to (v). (i) a hydroxy group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino) and (v) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (x) a 9- to 14-membered bicyclic non-aromatic heterocyclylcarbonyl group (e.g., tetrahydroimidazopyrazinylcarbonyltetrahydrotriazolopyrazinylcarbonyl), (y) 1 to 3 Cs, if necessary 1-6 5- or 6-membered monocyclic aromatic heterocyclylcarbamoyl groups (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl) substituted with an alkyl group (e.g., methyl); (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group optionally substituted with 1 to 3 substituents selected from (i) to (iv) (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl). (i) an oxo group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 Alkyl-carbonyl groups (e.g., acetyl) and (iv) C 7-16 aralkyl groups (e.g., benzyl) and (aa) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) Pyridine ring (optionally oxidized) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (m) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) an amino group, (d) a carbamoyl group, (e) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (f) C optionally substituted with 1 to 3 substituents selected from (i) to (iv) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) C 1-6 alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (g) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl), (j) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (k) optionally 1 to 3 mono- or di-C 1-6 Mono- or di-C substituted with alkylamino groups (e.g., N,N-diethylamino) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N-ethylcarbamoyl); (l) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (m) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring optionally further substituted with 1 to 3 substituents selected from (a) to (d): (a) a cyano group, (b) an amino group, (c) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) and (d) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (4) a pyridazine ring optionally further substituted with 1 to 3 cyano groups; (5) A pyrazine ring optionally further substituted with 1 to 3 substituents selected from (a) to (c): (a) a cyano group, (b) C 1-6 alkyl groups (e.g., methyl) and (c) C 1-6 alkoxy groups (e.g., methoxy), (6) A pyrazole ring optionally further substituted with 1 to 3 substituents selected from (a) to (e): (a) a cyano group, (b) a carboxy group optionally substituted with 1 to 3 substituents selected from (i) to (viii): (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a hydroxy group, (iv) a carboxy group, (v) C 1-6 alkoxy groups (e.g., methoxy), (vi) C 7-16 aralkyloxy-carbonyl groups (e.g., benzyloxycarbonyl), (vii) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-ethylcarbamoyl, N-propylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) and (viii) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl), (c) C 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (d) 1 to 3 Cs, as the case may be 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkoxy-carbonyl groups (e.g., propoxycarbonyl, tert-butoxycarbonyl) and (e) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (7) An imidazole ring optionally further substituted with 1 to 3 substituents selected from (a) and (b). (a) a cyano group and (b) C 1-6 alkyl groups (e.g., methyl); (8) One or two more C's, if necessary. 1-6 a thiazole ring substituted with an alkyl group (e.g., methyl); (9) A thiophene ring optionally further substituted with 1 to 3 substituents selected from (a) to (d). (a) a cyano group, (b) a carboxy group, (c) C 1-6 Alkoxy-carbonyl groups (e.g., methoxycarbonyl) and (d) Mono- or di-C 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl); (10) Furan ring, (11) A dihydropyridine ring optionally further substituted with 1 to 4 substituents selected from (a) to (d): (a) a cyano group, (b) an oxo group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C optionally substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) a halogen atom (e.g., a fluorine atom), (II) cyano group and (III) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy, ethoxy) or (12) A dihydropyrimidine ring optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) a cyano group and (b) oxo group is.

[0087] In other embodiments, ring A 2 is more preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (d). (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (d) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy), (2) A pyridine ring (optionally oxidized) optionally further substituted with 1 to 4 substituents selected from (a) to (c). (a) a cyano group, (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6alkyl groups (e.g., methyl) and (c) C 1-6 alkoxy groups (e.g., methoxy, ethoxy); (3) A pyrimidine ring optionally further substituted with 1 to 3 substituents selected from (a) and (b). (a) a cyano group and (b) C 1-6 an alkoxy group (e.g., methoxy) or (4) A dihydropyridine ring optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) a cyano group, (b) an oxo group and (b) C 1-6 It is an alkyl group (eg, methyl).

[0088] In other embodiments, ring A 2 is preferably a benzene ring, a 6-membered aromatic heterocycle, or a 6-membered non-aromatic heterocycle, each of which is further substituted with one cyano group and is optionally further substituted.

[0089] The "6-membered aromatic heterocycle" is preferably a pyridine ring (optionally oxidized), a pyrimidine ring, a pyridazine ring or a pyrazine ring, particularly preferably a pyridine ring. The "6-membered non-aromatic heterocycle" is preferably a dihydropyridine ring or a dihydropyrimidine ring.

[0090] A "benzene ring", a "6-membered aromatic heterocycle" and a "6-membered non-aromatic heterocycle" are rings of the formula: [ka] In addition to the partial structure represented by the following formula, it has one cyano group and optionally has 1 to 5 (preferably 1 to 3) substituents at substitutable positions.

[0091] Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds two, the respective substituents may be the same or different. Furthermore, the above-mentioned Substituent Group A is optionally substituted with a substituent selected from the Substituent Group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, the respective substituents may be the same or different.

[0092] Ring A 2 is more preferably (1) Benzene ring further substituted with one cyano group, and Optionally, further substituted with 1 to 5 substituents selected from (a) to (q) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine) optionally fused with a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); is further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) to (h) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) 6-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) is further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl groups (e.g., methyl) is.

[0093] In other embodiments, ring A 2 is more preferably (1) Benzene ring further substituted with one cyano group, and Optionally, further substituted with 1 to 5 substituents selected from (a) to (q) (a) a cyano group, (b) a halogen atom (e.g., a fluorine atom), (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 In the case of alkyl groups (e.g., methyl, ethyl), (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine) optionally fused with a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); is further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) 6-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) is further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl groups (e.g., methyl) is.

[0094] In other embodiments, ring A 2 is more preferably (1) Benzene ring further substituted with one cyano group, and Optionally, further substituted with 1 to 5 substituents selected from (a) to (c) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 alkoxy groups (e.g., methoxy) and (c) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy); (2) 6-membered aromatic heterocycles (e.g., pyridine, pyrimidine) further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkyl groups (e.g., methyl) and (b) C 1-6 alkoxy groups (e.g., methoxy, ethoxy); or (3) 6-membered non-aromatic heterocycles (e.g., dihydropyridine) further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C 1-6 alkyl group (e.g., methyl) is.

[0095] Ring A 2 is even more preferably (1) Benzene ring further substituted with one cyano group, and Optionally, further substituted with 1 to 5 substituents selected from (a) to (q) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) Pyridine ring (optionally oxidized) optionally fused with a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); is further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (3) Pyrimidine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 3 substituents selected from (a) to (c) (a) an amino group, (b) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino); (4) a pyridazine ring further substituted with one cyano group; (5) Pyrazine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 3 substituents selected from (a) and (b) (a) C 1-6 alkyl groups (e.g., methyl) and (b) C 1-6 alkoxy groups (e.g., methoxy); (6) Dihydropyridine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkyl group (e.g., methyl) or (7) Dihydropyrimidine ring is further substituted with one cyano group, and optionally further substituted with one or two oxo groups is.

[0096] In other embodiments, ring A 2 is even more preferably (1) Benzene ring further substituted with one cyano group, and Optionally, further substituted with 1 to 5 substituents selected from (a) to (q) (a) a cyano group, (b) a halogen atom (e.g., a fluorine atom), (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 In the case of alkyl groups (e.g., methyl, ethyl), (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) Pyridine ring (optionally oxidized) optionally fused with a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); is further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (3) Pyrimidine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 3 substituents selected from (a) to (c) (a) an amino group, (b) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino); (4) a pyridazine ring further substituted with one cyano group; (5) Pyrazine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 3 substituents selected from (a) and (b) (a) C 1-6 alkyl groups (e.g., methyl) and (b) C 1-6 alkoxy groups (e.g., methoxy); (6) Dihydropyridine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkyl group (e.g., methyl) or (7) Dihydropyrimidine ring is further substituted with one cyano group, and optionally further substituted with one or two oxo groups is.

[0097] In other embodiments, ring A 2 is even more preferably (1) Benzene ring further substituted with one cyano group, and Optionally, further substituted with 1 to 5 substituents selected from (a) to (c) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 alkoxy groups (e.g., methoxy) and (c) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy); (2) Pyridine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkyl groups (e.g., methyl) and (b) C 1-6 alkoxy groups (e.g., methoxy, ethoxy); (3) Pyrimidine ring further substituted with one cyano group, and Optionally, 1 to 4 more C 1-6 substituted with an alkoxy group (e.g., methoxy); or (4) Dihydropyridine ring further substituted with one cyano group, and Optionally, further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C 1-6 alkyl group (e.g., methyl) is.

[0098] In other embodiments, ring A 2 is more preferably of the formula: [ka] wherein ring A is a partial structure represented by 3 is an optionally further substituted benzene ring, an optionally further substituted 6-membered nitrogen-containing aromatic heterocycle, or an optionally further substituted 6-membered nitrogen-containing non-aromatic heterocycle. A cyano group can be represented by the formula [ka] is bonded to a carbon atom adjacent to the carbon atom to which the partial structure represented by

[0099] The "6-membered nitrogen-containing aromatic heterocycle" of the "optionally further substituted 6-membered nitrogen-containing aromatic heterocycle" is preferably a pyridine ring (optionally oxidized), a pyrimidine ring, a pyridazine ring or a pyrazine ring, particularly preferably a pyridine ring. The "6-membered nitrogen-containing non-aromatic heterocycle" of the "optionally further substituted 6-membered nitrogen-containing non-aromatic heterocycle" is preferably a dihydropyridine ring or a dihydropyrimidine ring.

[0100] The "benzene ring" of the "optionally further substituted benzene ring", the "6-membered nitrogen-containing aromatic heterocycle" of the "optionally further substituted 6-membered nitrogen-containing aromatic heterocycle" and the "6-membered nitrogen-containing non-aromatic heterocycle" of the "optionally further substituted 6-membered nitrogen-containing non-aromatic heterocycle" are each independently selected from the group consisting of a cyano group and a ring of formula: [ka] In addition to the partial structure represented by the following formula, it may further have 1 to 3 substituents at substitutable positions.

[0101] Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds two, the respective substituents may be the same or different. Furthermore, the above-mentioned Substituent Group A is optionally substituted with a substituent selected from the Substituent Group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, the respective substituents may be the same or different.

[0102] Ring A 3 is preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (q): (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) A 6-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl groups (e.g., methyl) is.

[0103] In other embodiments, ring A 3 is preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (q): (a) a cyano group, (b) a halogen atom (e.g., a fluorine atom), (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 In the case of alkyl groups (e.g., methyl, ethyl), (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) A 6-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl groups (e.g., methyl) is.

[0104] In other embodiments, ring A 3 is preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (c). (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 alkoxy groups (e.g., methoxy) and (c) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy), (2) A 6-membered aromatic heterocycle (e.g., pyridine, pyrimidine) optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkyl groups (e.g., methyl) and (b) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) or (3) A 6-membered non-aromatic heterocycle (e.g., dihydropyridine) optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C 1-6 Alkyl groups (e.g., methyl) is.

[0105] Ring A 3 is more preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (q): (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) Pyridine ring (optionally oxidized) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring optionally further substituted with 1 to 3 substituents selected from (a) to (c): (a) an amino group, (b) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (4) pyridazine ring, (5) A pyrazine ring optionally further substituted with 1 to 3 substituents selected from (a) and (b). (a) C 1-6 alkyl groups (e.g., methyl) and (b) C 1-6 alkoxy groups (e.g., methoxy), (6) A dihydropyridine ring optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 an alkyl group (e.g., methyl) or (7) A dihydropyrimidine ring optionally further substituted with one or two oxo groups.

[0106] In other embodiments, ring A 3 is more preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (q): (a) a cyano group, (b) a halogen atom (e.g., a fluorine atom), (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 In the case of alkyl groups (e.g., methyl, ethyl), (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix):1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy)1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) Pyridine ring (optionally oxidized) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring optionally further substituted with 1 to 3 substituents selected from (a) to (c): (a) an amino group, (b) C 1-6 alkoxy groups (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (4) pyridazine ring, (5) A pyrazine ring optionally further substituted with 1 to 3 substituents selected from (a) and (b). (a) C 1-6 alkyl groups (e.g., methyl) and (b) C 1-6 alkoxy groups (e.g., methoxy), (6) A dihydropyridine ring optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 an alkyl group (e.g., methyl) or (7) A dihydropyrimidine ring optionally further substituted with one or two oxo groups. is.

[0107] In other embodiments, ring A 3 is more preferably (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (c). (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 alkoxy groups (e.g., methoxy) and (c) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy), (2) A pyridine ring optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkyl groups (e.g., methyl) and (b) C 1-6alkoxy groups (e.g., methoxy, ethoxy); (3) Optionally, 1 to 4 more Cs 1-6 a pyrimidine ring substituted with an alkoxy group (e.g., methoxy) or (4) A dihydropyridine ring optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C 1-6 Alkyl groups (e.g., methyl) is.

[0108] formula [ka] The partial structure represented by the formula (A 3 -1)~(A 3 -9); [ka] [During the ceremony, Q 1 is N or CR Q1 where R Q1 teeth (a) a hydrogen atom, (b) a cyano group, (c) a halogen atom, (d) a hydroxy group, (e) a carboxy group, (f) amino group, (g) optionally substituted C 1-6 alkyl groups, (h) optionally substituted C 1-6 alkoxy groups, (I C 1-6 alkyl-carbonyl groups, (j) C 1-6 alkoxy-carbonyl groups, (k) optionally substituted mono- or di-C 1-6 alkylamino groups, (l) optionally substituted mono- or di-C 1-6alkyl-carbonylamino groups, (m) Mono- or Di-C 1-6 alkoxy-carbonylamino groups, (n) Mono- or Di-C 1-6 alkyl-carbamoyl groups, (o) The-C 1-6 alkylsulfinylideneamino group, (p) C 3-10 cycloalkyl groups, (q) optionally substituted C 3-10 cycloalkyloxy groups, (r) a 3- to 8-membered monocyclic non-aromatic heterocyclic group, (s) optionally substituted 3- to 8-membered monocyclic non-aromatic heterocyclyloxy; (t) an optionally substituted 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group or (u) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group and Q 2 is N or CR Q2 where R Q2 teeth (a) a hydrogen atom, (b) a halogen atom or (c) C 1-6 alkoxy group and Q 3 is N or CR Q3 where R Q3 teeth (a) a hydrogen atom, (b) a cyano group, (c) a halogen atom, (d) a carboxy group, (e) optionally substituted C 1-6 alkyl groups, (f) optionally substituted C 1-6 alkoxy groups, (g) C 1-6 alkyl-carbonyl groups, (h) C 1-6 alkoxy-carbonyl groups, (i) Mono- or di-C 1-6 alkylamino groups, (j) optionally substituted mono- or di-C 1-6 alkyl-carbamoyl groups, (k) Ji-C 1-6 Alkyl sulfinylidene amino group or (l) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group and Q 4 is N or CR Q4 where R Q4 teeth (a) a hydrogen atom or (b) Halogen atoms and Q 1 , Q 2 , Q 3 and Q 4 wherein each N is optionally oxidized; R N1 is a hydrogen atom or C 1-6 is an alkyl group; R N2 is a hydrogen atom or C 1-6 is an alkyl group; R N3 is a hydrogen atom or C 1-6 is an alkyl group; and R N4 is a C optionally substituted with a hydrogen atom or 1 to 3 halogen atoms 1-6 is an alkyl group. It is a partial structure represented by:

[0109] formula [ka] The partial structure represented by the formula (A 3 -1), (A 3 -2), (A 3 -3), (A 3 -5), (A 3 -6) or (A 3 -9); [ka] (wherein each symbol is as defined above.) It is a partial structure represented by:

[0110] Formula (A 3 -1), Q 1 is preferably N or CR Q1 where R Q1 teeth (a) a hydrogen atom, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms); (d) a hydroxy group, (e) a carboxy group, (f) amino group, (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (h) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl, oxetanyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (I C 1-6 alkyl-carbonyl groups (e.g., acetyl); (j) C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl), (k) mono- or di-C optionally substituted with 1 to 3 substituents selected from (i) to (ii): 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (l) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (m) Mono- or Di-C 1-6 alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino); (n) Mono- or Di-C 1-6alkyl-carbamoyl groups (e.g., N,N-dimethylcarbamoyl); (o) The-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (p) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (q) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (r) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (s) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (t) 1 to 3 Cs, if necessary 1-6 a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy); or (u) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) is.

[0111] In other embodiments, the compound of formula (A 3 -1), Q 1 is preferably N or CR Q1 where R Q1 teeth (a) a hydrogen atom, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms); (d) a hydroxy group, (e) a carboxy group, (f) amino group, (g) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms)1-6 In the case of alkyl groups (e.g., methyl, ethyl), (h) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl, oxetanyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (I C 1-6 alkyl-carbonyl groups (e.g., acetyl); (j) C 1-6alkoxy-carbonyl groups (e.g., methoxycarbonyl), (k) mono- or di-C optionally substituted with 1 to 3 substituents selected from (i) to (ii): 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (l) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (m) Mono- or Di-C 1-6 alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino); (n) Mono- or Di-C 1-6 alkyl-carbamoyl groups (e.g., N,N-dimethylcarbamoyl); (o) The-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (p) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (q) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (r) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (s) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (t) 1 to 3 Cs, if necessary 1-6a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy); or (u) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) is.

[0112] In other embodiments, the compound of formula (A 3 -1), Q 1 is preferably CR Q1 where R Q1 teeth (a) a hydrogen atom, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 an alkoxy group (e.g., methoxy) or (d) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (eg, methoxy, ethoxy).

[0113] Formula (A 3 -1), Q 2 is preferably N (optionally oxidized) or CR Q2 where R Q2 teeth (a) a hydrogen atom, (b) a halogen atom (e.g., a fluorine atom) or (c) C 1-6 An alkoxy group (eg, methoxy).

[0114] In other embodiments, the compound of formula (A 3 -1), Q 2 is preferably CRQ2 where R Q2 teeth (a) a hydrogen atom or (b) A halogen atom (for example, a fluorine atom).

[0115] Formula (A 3 -1), Q 3 is preferably N (optionally oxidized) or CR Q3 where R Q3 teeth (a) a hydrogen atom, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms); (d) a carboxy group, (e) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (f) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy), (g) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (h) C 1-6 alkoxy-carbonyl groups (e.g., ethoxycarbonyl), (i) Mono- or di-C 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino); (j) No- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl). 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N-ethylcarbamoyl); (k) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino) or (l) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) is.

[0116] In other embodiments, the compound of formula (A 3 -1), Q 3 is preferably N (optionally oxidized) or CR Q3 where R Q3 teeth (a) a hydrogen atom, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms); (d) a carboxy group, (e) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (f) C 1-6 alkoxy groups (e.g., methoxy), (g) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (h) C 1-6 alkoxy-carbonyl groups (e.g., ethoxycarbonyl), (i) Mono- or di-C 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino); (j) No- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl). 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N-ethylcarbamoyl); (k) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino) or (l) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) is.

[0117] In other embodiments, the compound of formula (A 3 -1), Q 3 is preferably CR Q3 where R Q3 teeth (a) a hydrogen atom, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 an alkyl group (e.g., methyl) or (d) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy) is.

[0118] Formula (A 3 -1), Q 4 is preferably N (optionally oxidized) or CR Q4 where R Q4 teeth (a) a hydrogen atom or (b) Halogen atoms (e.g., fluorine atoms) is.

[0119] In other embodiments, the compound of formula (A 3 -1), Q 4 is preferably N (optionally oxidized) or CH is.

[0120] In other embodiments, the compound of formula (A 3 -1), Q 4 is preferably N or CR Q4 where R Q4 teeth (a) a hydrogen atom or (b) Halogen atoms (e.g., fluorine atoms) is.

[0121] Formula (A 3 -2) In R N1 is preferably a hydrogen atom or C 1-6 alkyl groups (e.g., methyl); Q 3 is preferably CH, and Q 4 is preferably CH.

[0122] Formula (A 3 -3) In R N2 is preferably a hydrogen atom or C 1-6 alkyl groups (e.g., methyl); Q 3 is preferably CH, and Q 4 is preferably N or CH.

[0123] Formula (A 3 -5) R N4 is preferably a hydrogen atom, Q 1 is preferably CH, and Q 2 is preferably CH.

[0124] Formula (A 3 -6), R N2 is preferably a hydrogen atom or C 1-6 alkyl groups (e.g., methyl); Q 1 is preferably CH, and Q 4 is preferably CH.

[0125] Formula (A 3 -9), R N4 is preferably a hydrogen atom or C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms). 1-6 an alkyl group (e.g., methyl), Q 2 is preferably CH, and Q 3 is preferably CH.

[0126] Ring B 1 is an optionally further substituted aromatic heterocycle. The "aromatic heterocycle" of the "optionally further substituted aromatic heterocycle" is -VZ-ring B 1 In addition, it optionally further has 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds 2, the respective substituents may be the same or different. The "aromatic heterocycle" of the "optionally further substituted aromatic heterocycle" is preferably a 5-membered aromatic heterocycle.

[0127] Ring B 1 is preferably ring B 2 , i.e., an optionally further substituted five-membered aromatic heterocycle. The "5-membered aromatic heterocycle" in the "optionally further substituted 5-membered aromatic heterocycle" is -O-CH(R 1 )-CH2-Ring B 2 In addition, it optionally further has 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds 2, the respective substituents may be the same or different. The "5-membered aromatic heterocycle" of the "optionally further substituted 5-membered aromatic heterocycle" is preferably a 5-membered nitrogen-containing aromatic heterocycle. Examples of 5-membered nitrogen-containing aromatic heterocycles include tetrazole, 1,2,3-triazole, 1,2,4-triazole, pyrazole, imidazole, pyrrole, thiazole, isothiazole, oxazole, isoxazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole, and the like.

[0128] Ring B 2 teeth Preferably an optionally further substituted 5-membered nitrogen-containing aromatic heterocycle, More preferably, it is a tetrazole or a triazole, each of which is optionally further substituted; Even more preferably, a tetrazole or a triazole, Even more preferred is a tetrazole or triazole, each of which is attached at its nitrogen. Even more preferably, it is a tetrazole or a 1,2,4-triazole, each of which is attached at its nitrogen; Particularly preferred is tetrazol-1-yl or 1,2,4-triazol-1-yl.

[0129] V is O, S, S(O), S(O)2 or N(R V ), where R V is a hydrogen atom or an optionally substituted C 1-6 It is an alkyl group. "Optionally substituted C 1-6 "C" in "Alkyl group" 1-6 The "alkyl group" optionally further has 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds two, the respective substituents may be the same or different. V is preferably O.

[0130] Z is an optionally substituted C 1-6 It is an alkylene group. "Optionally substituted C 1-6 Alkylene group "C 1-6 The alkylene group optionally further has 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of the substituents include those selected from the above-mentioned Substituent Group A. When the number of substituents exceeds two, the respective substituents may be the same or different. Z is preferably an optionally substituted ethylene group, more preferably -CH(R 1)-CH2-, where R 1 is C 1-6 It is an alkyl group. R 1 is preferably methyl. Z is particularly preferably -CH(CH3)-CH2-.

[0131] Compound (I) is preferably compound (II), more preferably compound (III).

[0132] Compound (I) is represented by the formulas (I-1) and (I-2): [ka] (wherein each symbol is as defined above.) The compound includes a compound represented by: Compound (II) has the formulas (II-1) and (II-2): [ka] (wherein each symbol is as defined above.) The compound includes a compound represented by: Compound (III) has the formulas (III-1) and (III-2): [ka] (wherein each symbol is as defined above.) The compound includes a compound represented by:

[0133] Preferred compounds (I) to (III) are as follows:

[0134] [Compound A] Compound (II) [wherein, X 1 is N or CR X1 where R X1 is a hydrogen atom, a halogen atom (e.g., a fluorine atom) or C 1-6 is an alkyl group (e.g., methyl); X 2 , X3 and X 4 are each independently C or N, and X 2 , X 3 and X 4 one is N and the other two are C; Ring A 2 teeth (1) Benzene ring [optionally fused with a 5- to 6-membered monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the fused ring is dihydrobenzofuran, isoindoline), and optionally (a) an oxo group and (b) 1 to 3 Cs, if necessary 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Optionally, further substituted with 1 to 5 substituents selected from (a) to (aa) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms); (c) a hydroxy group, (d) a carboxy group, (e) a formyl group, (f) amino group, (g) a carbamoyl group, (h) C optionally substituted with 1 to 3 substituents selected from (i) to (v) 1-6 Alkyl groups (e.g., methyl, ethyl, isopropyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a hydroxy group, (iii) C 1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino) and (v) Ji-C 1-6 Alkyl sulfinylidene amino group (e.g., N-dimethyl sulfinylidene amino) (I C 2-6 alkenyl groups (e.g., vinyl), (j) C 2-6 alkynyl groups (e.g., ethynyl), (k) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (l) C 1-6alkyl-carbonyl groups (e.g., acetyl); (m) C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (o) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino); (p) mono- or di-C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl, N-propylcarbamoyl, N-butylcarbamoyl, N-isobutylcarbamoyl, N-isopentylcarbamoyl, N-neopentylcarbamoyl) (i) a hydroxy group, (ii) C 1-6 alkoxy groups (e.g., methoxy), (iii) mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino, N,N-diethylamino); (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (v) Mono- or di-C 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-diethylcarbamoyl); (vi) C 3-10 cycloalkyl groups (e.g., cyclopropyl, cyclohexyl); (vii) C 6-14 aryl groups (e.g., phenyl); (viii) 5- or 6-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (III) (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxidethiomorpholinyl, tetrahydropyranyl). (I) a hydroxy group, (II) oxo group and (III) C 1-6 Alkyl groups (e.g., methyl) (q) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (r) C optionally substituted with 1 to 3 substituents selected from (i) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy) (i) 1 to 3 Cs, if necessary 1-6 3-8 membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with alkyl group (e.g., methyl) (s) C 3-10 cycloalkylsulfonyl-carbamoyl groups (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 aryl-carbamoyl groups (e.g., phenylcarbamoyl); (u) 1 to 3 Cs, if necessary 1-6 a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl, piperazinyl) substituted with an alkyl-carbonyl group (e.g., acetyl); (v) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (w) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl, piperidylcarbonyl, morpholinylcarbonyl) optionally substituted with 1 to 3 substituents selected from (i) to (v). (i) a hydroxy group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 alkoxy groups (e.g., methoxy), (iv) mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino) and (v) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (x) a 9- to 14-membered bicyclic non-aromatic heterocyclylcarbonyl group (e.g., tetrahydroimidazopyrazinylcarbonyltetrahydrotriazolopyrazinylcarbonyl), (y) 1 to 3 Cs, if necessary 1-6 5- or 6-membered monocyclic aromatic heterocyclylcarbamoyl groups (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl) substituted with an alkyl group (e.g., methyl); (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group optionally substituted with 1 to 3 substituents selected from (i) to (iv) (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl). (i) an oxo group, (ii) C 1-6 alkyl groups (e.g., methyl); (iii) C 1-6 Alkyl-carbonyl groups (e.g., acetyl) and (iv) C 7-16 aralkyl groups (e.g., benzyl) and (aa) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 5- or 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (n) (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a carboxy group, (d) amino groups, (e) a carbamoyl group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (viii) 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a hydroxy group, (iv) a carboxy group, (v) C 1-6 alkoxy groups (e.g., methoxy), (vi) C 7-16 aralkyloxy-carbonyl groups (e.g., benzyloxycarbonyl), (vii) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-ethylcarbamoyl, N-propylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) and (viii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (iv) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) C 1-6 alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (h) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (I C 1-6 alkyl-carbonyl groups (e.g., acetyl); (j) 1 to 3 Cs, as the case may be 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl), (k) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (l) mono- or di-C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl) (I C 1-6 alkoxy groups (e.g., methoxy) and (II) Mono- or di-C 1-6 Alkylamino groups (e.g., N,N-diethylamino) (m) Mono- or Di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (n) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) A 5- or 6-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) optionally further substituted with 1 to 4 substituents selected from (a) to (d). (a) an oxo group, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C optionally substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) a halogen atom (e.g., a fluorine atom), (II) cyano group and (III) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) and; Y 1 is N or CH; Y 2 is N or CR Y2 where R Y2 is a hydrogen atom, a halogen atom (e.g., a fluorine atom, a chlorine atom) or a cyano group; Y 3 is N or CR Y3 where R Y3 is a hydrogen atom or a halogen atom (e.g., a fluorine atom); Y 4 is N or CR Y4 where R Y4 is a hydrogen atom or a halogen atom (e.g., a fluorine atom); Ring B 2 is a 5-membered aromatic heterocycle (preferably a tetrazole or triazole (preferably a 1,2,4-triazole), each of which is preferably attached at its nitrogen); and R 1 is C 1-6 It is an alkyl group (preferably methyl).

[0135] [Compound B] Compound (III) [wherein, X 2 , X 3 and X 4 are each independently C or N, and X 2 , X 3 and X 4 one is N and the other two are C; Ring A 3 teeth (1) A benzene ring optionally further substituted with 1 to 5 substituents selected from (a) to (q): (a) a cyano group, (b) halogen atoms (e.g., fluorine atoms, chlorine atoms); (c) a hydroxy group, (d) a carboxy group, (e) an amino group, (f) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C 1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (h) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (I C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkylamino groups (e.g., N-ethylamino), (k) 1 to 3 Cs, as the case may be 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (l) mono- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl); (m) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (n) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (o) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted by 1 to 3 oxo groups; (p) 1 to 3 Cs, if necessary 1-6 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl groups (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy), and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino), (2) 6-membered aromatic heterocycles (e.g., pyridine (optionally oxidized), pyrimidine, pyridazine, pyrazine) optionally fused to a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the fused ring is an imidazopyridine); and Optionally, further substituted with 1 to 4 substituents selected from (a) to (i) (a) a halogen atom (e.g., a fluorine atom, a chlorine atom), (b) an amino group, (c) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (d) C optionally substituted with 1 to 3 substituents selected from (i) to (iii) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) C 1-6 alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (f) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (g) mono- or di-C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino); (h) Mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino) and (i) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl) or (3) A 6-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) optionally further substituted with 1 to 4 substituents selected from (a) and (b). (a) an oxo group and (b) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl groups (e.g., methyl) and; Y 1 is N or CH; Y 2 is N or CR Y2 where R Y2 is a hydrogen atom or a halogen atom (e.g., a fluorine atom, a chlorine atom); Y 3 is N or CR Y3 where R Y3 is a hydrogen atom or a halogen atom (e.g., a fluorine atom); Y 4 is N or CR Y4 where R Y4 is a hydrogen atom or a halogen atom (e.g., a fluorine atom); and W is N or CH.

[0136] [Compound C] [Compound B] [wherein, formula; [ka] The partial structure represented by the formula (A 3 -1), (A 3 -2), (A 3 -3), (A 3 -5), (A 3 -6) or (A 3 -9); [ka] is a substructure represented by Formula (A 3 -1), Q 1 is N or CR Q1 where R Q1 teeth (a) a hydrogen atom, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms); (d) a hydroxy group, (e) a carboxy group, (f) amino group, (g) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (h) C optionally substituted with 1 to 3 substituents selected from (i) to (ix): 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a cyano group, (iii) a carboxy group, (iv) a carbamoyl group, (v) C optionally substituted with 1 to 3 substituents selected from (I) to (II) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (I C 1-6 Alkoxy-C1-6 Alkoxy groups (e.g., methoxyethoxy) and (II) Mono- or di-C 1-6 alkylamino groups (e.g., N,N-dimethylamino), (vi) Mono- or di-C 1-6 alkyl-carbonylamino groups (e.g., N-acetylamino); (vii) N.C. 1-6 Alkyl-NC 1-6 alkyl-carbonylamino groups (e.g., N-methyl-N-acetylamino); (viii) C 3-10 cycloalkyl groups (e.g., cyclobutyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted with 1 to 3 substituents selected from (I) to (II) (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl, oxetanyl). (I) oxo group and (II) C 1-6 Alkyl groups (e.g., methyl) (i) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl-carbonyl groups (e.g., acetyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (j) C 1-6 alkoxy-carbonyl groups (e.g., methoxycarbonyl), (k) Mono- or Di-C 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino) (l) 1 to 3 Cs, if necessary 1-6 Mono- or di-C substituted with alkoxy groups (e.g., methoxy) 1-6 alkyl-carbonylamino groups (e.g., N-propanoylamino); (m) Mono- or Di-C 1-6alkoxy-carbonylamino groups (e.g., N-tert-butoxycarbonylamino, N,N-di-tert-butoxycarbonylamino); (n) Mono- or Di-C 1-6 alkyl-carbamoyl groups (e.g., N,N-dimethylcarbamoyl); (o) The-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino); (p) C 3-10 cycloalkyl groups (e.g., cyclopropyl); (q) 1 to 3 Cs, if applicable 1-6 C substituted with a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) substituted with an alkyl group (e.g., methyl) 3-10 cycloalkyloxy groups (e.g., cyclohexyloxy), (r) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., azetidinyl, pyrrolidinyl), (s) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) optionally substituted with 1 to 3 oxo groups; (t) 1 to 3 Cs, if necessary 1-6 a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl) substituted with an alkoxy group (e.g., methoxy); or (u) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) and; Q 2 is N (possibly oxidized) or CR Q2 where R Q2 teeth (a) a hydrogen atom, (b) a halogen atom (e.g., a fluorine atom) or (c) C 1-6 Alkoxy groups (e.g., methoxy) and; Q 3 is N (possibly oxidized) or CRQ3 where R Q3 teeth (a) a hydrogen atom, (b) a cyano group, (c) halogen atoms (e.g., fluorine atoms, chlorine atoms); (d) a carboxy group, (e) C optionally substituted with 1 to 3 substituents selected from (i) to (ii) 1-6 Alkyl groups (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) Hydroxy group (f) C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 alkoxy groups (e.g., methoxy), (g) C 1-6 alkyl-carbonyl groups (e.g., acetyl); (h) C 1-6 alkoxy-carbonyl groups (e.g., ethoxycarbonyl), (i) Mono- or di-C 1-6 alkylamino groups (e.g., N-methylamino, N,N-dimethylamino); (j) No- or di-C optionally substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl). 1-6 alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N-ethylcarbamoyl); (k) Ji-C 1-6 alkylsulfinylideneamino groups (e.g., N-dimethylsulfinylideneamino) or (l) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) and Q 4 is N (possibly oxidized) or CR Q4 where R Q4 teeth (a) a hydrogen atom or (b) Halogen atoms (e.g., fluorine atoms) and; Formula (A 3 -2) In R N1 is a hydrogen atom or C 1-6 an alkyl group (e.g., methyl), Q 3 is CH, and Q 4 is CH; Formula (A 3 -3) In R N2 is a hydrogen atom or C 1-6 an alkyl group (e.g., methyl), Q 3 is CH, and Q 4 is N or CH; Formula (A 3 -5) R N4 is a hydrogen atom, Q 1 is CH, and Q 2 is CH; Formula (A 3 -6), R N2 is a hydrogen atom or C 1-6 an alkyl group (e.g., methyl), Q 1 is CH, and Q 4 is CH; and Formula (A 3 -9), R N4 is a hydrogen atom or C optionally substituted with 1 to 3 halogen atoms (e.g., fluorine atoms). 1-6 an alkyl group (e.g., methyl), Q 2 is CH, and Q 3 is CH.

[0137] [Compound D] 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 121); 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]pyridine-3-carbonitrile or a pharmaceutically acceptable salt (Example 247); 2-[6-(3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]pyridine-3-carbonitrile or a pharmaceutically acceptable salt (Example 271); 2-[5-(3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile or a pharmaceutically acceptable salt (Example 284); 4-fluoro-2-[6-(5-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-3-yl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 288); 4-methoxy-2-[6-(3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]pyridine-3-carbonitrile or a pharmaceutically acceptable salt (Example 300); 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]-4-methoxypyridine-3-carbonitrile or a pharmaceutically acceptable salt (Example 321); 4-fluoro-2-[5-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 345); 4-fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyrazin-2-yl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 392); 4-fluoro-2-methoxy-6-[5-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 393); and 4-Fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}pyridin-2-yl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 410).

[0138] Specific examples of Compound (I) include the compounds of Examples 1-486.

[0139] When Compound (I) is a salt, examples of the salt include metal salts, ammonium salts, salts with organic bases, salts with inorganic acids, salts with organic acids, and salts with basic or acidic amino acids. Preferred metal salts include alkali metal salts, such as sodium salts and potassium salts; alkaline earth metal salts, such as calcium salts, magnesium salts, and barium salts; and aluminum salts. Preferred examples of salts with organic bases include salts with trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N,N'-dibenzylethylenediamine, etc. Preferred examples of salts with inorganic acids include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc. Examples of preferred salts with organic acids include salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. Examples of preferred salts with basic amino acids include salts with arginine, lysine, ornithine, etc. Examples of preferred salts with acidic amino acids include salts with aspartic acid, glutamic acid, etc. Among these, pharmaceutically acceptable salts are preferred. For example, when a compound has an acidic functional group, examples of salts include inorganic salts such as alkali metal salts (e.g., sodium salt, potassium salt, etc.), alkaline earth metal salts (e.g., calcium salt, magnesium salt, etc.), ammonium salts, etc.; when a compound has a basic functional group, examples of salts include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc., and salts with organic acids such as acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. When compound (I) includes isomers such as tautomers, optical isomers, stereoisomers, positional isomers, and rotational isomers, any of the isomers or mixtures thereof are also included in the compound of the present invention. Furthermore, when compound (I) includes optical isomers, the optical isomers separated from the racemate are included in compound (I). Compound (I) can be obtained in crystalline form. Compound (I) can include both a single crystalline form and a crystalline mixture. Compound (I) may be a pharmaceutically acceptable cocrystal or cocrystal salt. As used herein, a cocrystal or cocrystal salt refers to a crystalline substance consisting of two or more distinct solids at room temperature, each of which has unique physical characteristics such as structure, melting point and heat of fusion, hygroscopicity, solubility, and stability. A cocrystal or cocrystal salt can be prepared by a cocrystallization method known per se. Compound (I) may be a solvate (for example, a hydrate) or a non-solvate, and both are encompassed by Compound (I). Isotopes (e.g., 2 H, 3 H, 11 C. 14 C. 18 F, 35 S, 125 Compounds labeled or substituted with isotopes (e.g., I) are also encompassed by compound (I). Compounds labeled or substituted with isotopes can be used, for example, as tracers (PET tracers) used in positron emission tomography (PET), and are expected to be useful in fields such as medical diagnosis.

[0140] Methods for preparing the compounds of the present invention are described below.

[0141] The raw material compounds and reagents used in each step of the following production methods and the resulting compounds may each be a salt, and examples of such salts include those similar to the salts of the compounds of the present invention.

[0142] When the compound obtained in each step is in a free form, it can be converted into the desired salt by a method known per se. When the compound obtained in each step is in a salt form, it can be converted into the desired free form or another salt by a method known per se.

[0143] The compound obtained in each step can be used in the next reaction directly as a reaction mixture or as a crude product, or can be isolated or purified from the reaction mixture by a method known per se, such as concentration, crystallization, recrystallization, distillation, solvent extraction, fractional distillation, column chromatography, or other separation method.

[0144] When the raw material compounds and reagents used in each step are commercially available, the commercially available products can also be used directly.

[0145] In the reaction of each step, the reaction time varies depending on the types of reagents and solvents used, but is generally 1 minute to 48 hours, preferably 10 minutes to 8 hours, unless otherwise specified.

[0146] In the reactions of each step, the reaction temperature varies depending on the types of reagents and solvents used, but is generally −78° C. to 300° C., preferably −78° C. to 150° C., unless otherwise specified.

[0147] In the reaction of each step, the pressure varies depending on the types of reagents and solvents used, but is generally 1 to 20 atmospheres, preferably 1 to 3 atmospheres, unless otherwise specified.

[0148] A microwave synthesizer such as Biotage Initiator can be used in the reactions in each step. The reaction temperature varies depending on the types of reagents and solvents used, but is generally room temperature to 300°C, preferably 50°C to 250°C, unless otherwise specified. The reaction time varies depending on the types of reagents and solvents used, but is generally 1 minute to 48 hours, preferably 1 minute to 8 hours, unless otherwise specified.

[0149] In the reactions of each step, unless otherwise specified, the reagents are used in an amount of 0.5 to 20 equivalents, preferably 0.8 to 5 equivalents, relative to the substrate. When the reagents are used as catalysts, they are used in an amount of 0.001 to 1 equivalent, preferably 0.01 to 0.2 equivalents, relative to the substrate. When the reagents are used as ligands, they are used in an amount of 0.001 to 1 equivalent, preferably 0.01 to 0.2 equivalents, relative to the substrate. When the reagents are used as reaction solvents, they are used in the amount of the solvent.

[0150] Unless otherwise specified, the reaction in each step is carried out without a solvent or by dissolving or suspending the raw material compounds in a suitable solvent. Examples of the solvent include those described in the Examples and the following solvents. Alcohols: methanol, ethanol, tert-butyl alcohol, 2-methoxyethanol, benzyl alcohol, etc.; Ethers: diethyl ether, diphenyl ether, tetrahydrofuran, 1,2-dimethoxyethane, etc.; Aromatic hydrocarbons: chlorobenzene, toluene, xylene, etc.; Saturated hydrocarbons: cyclohexane, hexane, etc.; Amides: N,N-dimethylformamide, N-methylpyrrolidone, etc.; Halogenated hydrocarbons: dichloromethane, carbon tetrachloride, etc.; Nitriles: such as acetonitrile; Sulfoxides: such as dimethyl sulfoxide; Aromatic organic bases: pyridine, etc.; Anhydrides: acetic anhydride, etc.; Organic acids: formic acid, acetic acid, trifluoroacetic acid, etc.; Inorganic acids: hydrochloric acid, sulfuric acid, etc.; Esters: ethyl acetate, etc.; Ketones: acetone, methyl ethyl ketone, etc.; water. The above solvents may be used in a mixture of two or more in an appropriate ratio.

[0151] When a base is used in the reaction in each step, examples thereof include those described in the Examples and the following bases. Inorganic bases: sodium hydroxide, magnesium hydroxide, sodium carbonate, calcium carbonate, sodium bicarbonate, etc.; Organic bases: triethylamine, diethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]-7-undecene, imidazole, piperidine, etc.; Metal alkoxides: sodium ethoxide, potassium tert-butoxide, etc.; Alkali metal hydrides: sodium hydride, etc.; Metal amides: sodium amide, lithium diisopropylamide, lithium hexamethyldisilazide, etc.; Organolithium: n-butyllithium, etc.

[0152] When an acid or acid catalyst is used in the reaction in each step, examples include those described in the Examples and the following acids and acid catalysts. Inorganic acids: hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, phosphoric acid, etc.; Organic acids: acetic acid, trifluoroacetic acid, citric acid, p-toluenesulfonic acid, 10-camphorsulfonic acid, etc.; Lewis acids: boron trifluoride diethyl ether complex, zinc iodide, anhydrous aluminum chloride, anhydrous zinc chloride, anhydrous iron chloride, etc.

[0153] Unless otherwise specified, the reactions in each step are carried out by a method known per se, for example, the method described in Experimental Chemistry Lectures, 5th Edition, Vols. 13-19 (edited by the Chemical Society of Japan); New Experimental Chemistry Lectures, Vols. 14-15 (edited by the Chemical Society of Japan); Precision Organic Synthesis, Revised 2nd Edition (L.F. Tietze and Th. Eicher, Nankodo); Revised Organic Named Reactions: Their Mechanisms and Key Points (Hideo Togo, Kodansha); ORGANIC SYNTHESES Collective Volumes I-VII (John Wiley & Sons Inc.); Modern Organic Synthesis in the Laboratory: A Collection of Standard Experimental Procedures (Jie Jack Li, OXFORD UNIVERSITY); Comprehensive Heterocyclic Chemistry III, Vols. 1-14 (Elsevier Japan); Organic Synthesis Strategies Learned from Named Reactions (translated by Kiyoshi Tomioka, Kagaku Dojin); Comprehensive Organic Transformations (VCH Publishers Inc.), 1989, or the method described in the Examples.

[0154] In each step, protection or deprotection of functional groups is carried out by a method known per se, for example, by the method described in "Protective Groups in Organic Synthesis, 4th Ed," Wiley-Interscience, Inc., 2007 (Theodora W. Greene, Peter GM Wuts); "Protecting Groups 3rd Ed." Thieme, 2004 (PJ Kocienski), or the like, or by the method described in the Examples. Examples of the protecting group for a hydroxy group such as an alcohol and a phenolic hydroxy group include ether-type protecting groups such as methoxymethyl ether, benzyl ether, tert-butyldimethylsilyl ether, tetrahydropyranyl ether, etc.; carboxylate ester-type protecting groups such as acetate ester, etc.; sulfonate ester-type protecting groups such as methanesulfonate ester, etc.; and carbonate ester-type protecting groups such as tert-butyl carbonate, etc. Examples of the protecting group for the carbonyl group of an aldehyde include acetal-type protecting groups such as dimethyl acetal; and cyclic acetal-type protecting groups such as 1,3-dioxane. Examples of the protecting group for the carbonyl group of a ketone include ketal-type protecting groups, such as dimethyl ketal; cyclic ketal-type protecting groups, such as 1,3-dioxane; oxime-type protecting groups, such as O-methyloxime; and hydrazone-type protecting groups, such as N,N-dimethylhydrazone. Examples of the protecting group for a carboxyl group include ester-type protecting groups such as methyl ester; and amide-type protecting groups such as N,N-dimethylamide. Examples of the thiol-protecting group include ether-type protecting groups, such as benzylthioether; and ester-type protecting groups, such as thioacetate, thiocarbonate, and thiocarbamate. Examples of protecting groups for amino groups and aromatic heterocycles such as imidazole, pyrrole, and indole include carbamate-type protecting groups such as benzylcarbamate; amide-type protecting groups such as acetamide; alkylamine-type protecting groups such as N-triphenylmethylamine; and sulfonamide-type protecting groups such as methanesulfonamide. The protecting group can be removed by methods known per se, for example, by using acids, bases, ultraviolet light, hydrazine, phenylhydrazine, sodium N-methyldithiocarbamate, tetrabutylammonium fluoride, palladium acetate, trialkylsilyl halides (e.g., trimethylsilyl iodide, trimethylsilyl bromide), reduction methods, etc.

[0155] When a reduction reaction is carried out in each step, examples of the reducing agent to be used include metal hydrides such as lithium aluminum hydride, sodium triacetoxyborohydride, sodium cyanoborohydride, diisobutylaluminum hydride (DIBAL-H), sodium borohydride, tetramethylammonium triacetoxyborohydride, etc.; boranes such as borane tetrahydrofuran complex, etc.; Raney nickel; Raney cobalt; hydrogen; formic acid; triethylsilane, etc. When a carbon-carbon double bond or triple bond, or a nitro group or a benzyloxycarbonyl group is reduced, a method using a catalyst such as palladium-carbon or Lindlar catalyst can be used.

[0156] When an oxidation reaction is carried out in each step, examples of the oxidizing agent to be used include peroxides, such as m-chloroperbenzoic acid (mCPBA), hydrogen peroxide, tert-butyl hydroperoxide, and the like; perchlorates, such as tetrabutylammonium perchlorate, and the like; chloric acids, such as sodium chlorate, and the like; chlorous acids, such as sodium chlorite, and the like; periodic acids, such as sodium periodate, and the like; hypervalent iodine reagents, such as iodosylbenzene, and the like; manganese-containing reagents, such as manganese dioxide, potassium permanganate, and the like; lead, such as lead tetraacetate, and the like; chromium-containing reagents, such as pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), Jones reagent, and the like; halogen compounds, such as N-bromosuccinimide (NBS), and the like; oxygen; ozone; sulfur trioxide-pyridine complex; osmium tetroxide; selenium dioxide; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), oxone, and the like.

[0157] When a radical reaction is carried out in each step, examples of the radical initiator to be used include azo compounds such as azobisisobutyronitrile (AIBN), water-soluble radical initiators such as 4-4'-azobis-4-cyanopentanoic acid (ACPA), triethylboron in the presence of air or oxygen, benzoyl peroxide, etc. Examples of the radical reagent to be used include tributylstannane, tristrimethylsilylsilane, 1,1,2,2-tetraphenyldisilane, diphenylsilane, samarium iodide, etc.

[0158] When a nucleophilic substitution reaction is carried out in each step, examples of the base to be used include organolithium (e.g., lithium bis(trimethylsilyl)amide), metal alkoxide (e.g., potassium tert-butoxide), alkali metal hydride (e.g., sodium hydride), inorganic base, organic base, etc.

[0159] When carrying out the aromatic nucleophilic substitution reaction in each step, a combination of a nucleophile (e.g., hydroxy, amine, imidazole, etc.) and a base (e.g., organic base, etc.) or a combination of a nucleophile and an acid (e.g., organic acid, etc.) is used as a reagent.

[0160] When a nucleophilic addition reaction with a carbanion, a nucleophilic 1,4-addition reaction (Michael addition reaction) with a carbanion, or a nucleophilic substitution reaction with a carbanion is carried out in each step, examples of the base used for producing the carbanion include organolithium, metal alkoxide, inorganic base, organic base, etc.

[0161] When a Grignard reaction is carried out in each step, examples of the Grignard reagent to be used include aryl magnesium halides such as phenyl magnesium bromide, and alkyl magnesium halides such as methyl magnesium bromide. The Grignard reagent can be produced by a method known per se, for example, by reacting an alkyl halide or aryl halide with metallic magnesium in ether or tetrahydrofuran as a solvent.

[0162] When the azidation reaction of an alcohol, an alkyl halide, or a sulfonate is carried out in each step, examples of the azidation agent to be used include diphenylphosphoryl azide (DPPA), trimethylsilyl azide, sodium azide, etc. For example, for the azidation reaction of an alcohol, a method using diphenylphosphoryl azide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or a method using trimethylsilyl azide and a Lewis acid is used.

[0163] When a reductive amination reaction is carried out in each step, examples of the reducing agent to be used include sodium triacetoxyborohydride, sodium cyanoborohydride, borane-2-methylpyridine complex, hydrogen, formic acid, etc. When the substrate is an amine compound, examples of the carbonyl compound to be used include paraformaldehyde, aldehydes such as acetaldehyde, and ketones such as cyclohexanone. When the substrate is a carbonyl compound, examples of the amine to be used include ammonia, primary amines such as methylamine, and secondary amines such as dimethylamine.

[0164] When the Mitsunobu reaction is carried out in each step, a combination of an azodicarboxylate (e.g., diethyl azodicarboxylate (DEAD), diisopropyl azodicarboxylate (DIAD), etc.) and triphenylphosphine or a phosphorane reagent (e.g., cyanomethylene tributylphosphorane (Tsunoda reagent)) is used as the reagent.

[0165] When an esterification reaction, an amidation reaction or a urea-forming reaction is carried out in each step, the reagents used include acyl halides such as acid chlorides, acid bromides, etc.; activated carboxylic acids such as anhydrides, activated esters, sulfates, etc. Examples of carboxylic acid activating agents include carbodiimide condensing agents, such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCD); triazine condensing agents, such as 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n-hydrate (DMT-MM); carbonate condensing agents, such as 1,1-carbonyldiimidazole (CDI); diphenylphosphoryl azide (DPPA); benzotriazol-1-yloxy-trisdimethylaminophosphonium salt (BOP reagent); 2-chloro-1-methyl-pyridinium iodide (Mukaiyama reagent); thionyl chloride; lower alkyl haloformates, such as ethyl chloroformate; O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphorate (HATU); sulfuric acid; and combinations thereof. When a carbodiimide condensing agent is used, an additive such as 1-hydroxybenzotriazole (HOBt), N-hydroxysuccinimide (HOSu), dimethylaminopyridine (DMAP), or the like may be added to the reaction system.

[0166] When a coupling reaction is carried out in each step, examples of the metal catalyst to be used include palladium compounds such as palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), tris(dibenzylideneacetone)dipalladium(0), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II), (tri-tert-butylphosphine)palladium(0); nickel compounds such as tetrakis(triphenylphosphine)nickel(0); rhodium compounds such as tris(triphenylphosphine)rhodium(III) chloride; cobalt compounds; copper compounds such as copper oxide, copper(I) iodide, copper(II) diacetate; platinum compounds; Furthermore, a base may be added to the reaction system, examples of which include organic bases (e.g., 1,8-diazabicyclo[5.4.0]undec-7-ene, N,N-diisopropylethylamine), inorganic bases, etc. Furthermore, a ligand may be added to the reaction system, examples of which include organic amines such as N,N'-dimethylethylenediamine, N,N'-dimethyl-cyclohexane-1,2-diamine, 2,2-bipyridyl, etc.; organic phosphorus compounds such as triphenylphosphine, tri-tert-butylphosphine, 1,1'-bis(diphenylphosphino)ferrocene, di-tert-butyl(4-dimethylaminophenyl)phosphine, cataCXium® A (di(1-adamantyl)-n-butylphosphine), etc.

[0167] When a thiocarbonylation reaction is carried out in each step, diphosphorus pentasulfide is typically used as the thiocarbonylating agent. Alternatively, a reagent having a 1,3,2,4-dithiadiphosphetane-2,4-disulfide structure (e.g., 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawson's reagent)) can also be used instead of diphosphorus pentasulfide.

[0168] When the halogenation reaction of a hydroxy group is carried out in each step, examples of the halogenating agent to be used include hydrohalic acids and inorganic acids, particularly acid halides such as hydrochloric acid, thionyl chloride, and phosphorus oxychloride for chlorination, and 48% hydrobromic acid for bromination. Furthermore, a method for producing alkyl halides by reacting an alcohol with triphenylphosphine and carbon tetrachloride or carbon tetrabromide can be used. Alternatively, a two-step method for producing alkyl halides can also be used, in which an alcohol is converted to the corresponding sulfonate and then the sulfonate is reacted with lithium bromide, lithium chloride, or sodium iodide.

[0169] When a sulfonate esterification reaction is carried out in each step, examples of the sulfonating agent to be used include methanesulfonyl chloride, p-toluenesulfonyl chloride, methanesulfonic anhydride, p-toluenesulfonic anhydride, and the like.

[0170] When the hydrolysis reaction is carried out in each step, an acid or a base is used as a reagent. For the acid hydrolysis reaction of tert-butyl esters, formic acid, triethylsilane, etc. can be added to the by-produced reductively trapped tert-butyl cation.

[0171] When a dehydration reaction is carried out in each step, examples of the dehydrating agent to be used include sulfuric acid, diphosphorus pentoxide, phosphorus oxychloride, N,N'-dicyclohexylcarbodiimide, alumina, polyphosphoric acid, and the like.

[0172] When a cyanation reaction is carried out in each step, examples of the metal catalyst to be used include palladium compounds, such as chloro(2-dicyclohexylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II), palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), tris(dibenzylideneacetone), ) dipalladium(0), 1,1'-bis(diphenylphosphino)ferrocene palladium(II) chloride, (tri-tert-butylphosphine)palladium(0), etc.; nickel compounds such as tetrakis(triphenylphosphine)nickel(0); rhodium compounds such as tris(triphenylphosphine)rhodium(III) chloride; cobalt compounds; copper compounds such as copper oxide, copper(I) iodide, copper(II) diacetate, etc.; platinum compounds, etc. Examples of the cyano compound used include potassium hexacyanoferrate(II) trihydrate, copper(I) cyanide, zinc cyanide, potassium cyanide, sodium cyanide, etc. Furthermore, a base may be added to the reaction system, and examples thereof include organic bases, inorganic bases, etc. Furthermore, a ligand may be added to the reaction system, examples of which include organic amines such as N,N'-dimethylethylenediamine, N,N'-dimethyl-cyclohexane-1,2-diamine, 2,2-bipyridyl, etc.; organic phosphorus compounds such as 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, triphenylphosphine, tri-tert-butylphosphine, tricyclohexylphosphine, BINAP (2,2'-bis(diphenylphosphino)-1,1-binaphthyl), etc.

[0173] When nitration reaction is carried out in each step, examples of the nitrating agent to be used include mineral acids, such as acid mixtures, nitric acid, etc.; nitric acid, such as potassium nitrate, sodium nitrate, tetramethylammonium nitrate, silver nitrate, etc.

[0174] When O-alkylation or N-alkylation is carried out in each step, a combination of an alkylating agent (e.g., alkyl halide, alkyl sulfonate ester, etc.) and a base (e.g., organic base, inorganic base, alkali metal hydride, etc.) is used as a reagent.

[0175] Compound (I) of the present invention can be prepared by the method described below. A in the following scheme 1 , B 1 , V, X 1 ~X 6 , Y 1 ~Y 4 and Z is as defined above.

[0176] X 2 is C and X 3 and X 4 Compound (I), in which one of the groups is N and the other is C, can be produced from compound (2) by the method shown in Scheme 1-1. [Scheme 1-1] [ka] where L 1 ~L 4 are each independently a leaving group, and M 1 and M 2 are each independently a metal group, and T 1 is a leaving group or metal group, and the other symbols are as defined above.

[0177] L 1 ~L 4 and T 1 Examples of the "leaving group" include halogen atoms (e.g., fluorine, chlorine, bromine, iodine, etc.), optionally halogenated C 1-6 Alkyl sulfonyloxy groups (e.g., methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy, etc.), optionally substituted C 6-14 an arylsulfonyloxy group [e.g., optionally C 1-6C having 1 to 3 substituents selected from alkyl groups (e.g., methyl, etc.) 6-14 arylsulfonyloxy group], optionally halogenated C 1-6 Alkyl sulfide group, optionally substituted C 6-14 Aryl sulfide group, C 1-6 These include alkoxy groups (such as methoxy), nitro groups, m-nitrobenzenesulfonyloxy, and naphthylsulfonyloxy. M 1 , M 2 and T 1 Examples of "metal groups" are boronic acid groups (-B(OH)2) or boronic ester groups (-B(OR)2; R is C 1-6 alkyl groups) or cyclic groups thereof (for example, 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl, etc.) or trialkylstannyl groups. Compounds (2), (3), (7) and (9) may be commercially available products or may be prepared by methods known per se.

[0178] X 1 is CH and X 2 and X 4 is C and X 6 is CH and X 3 and X 5 Compound (I) in which is N can also be produced from compound (9) by the method shown in Scheme 1-2. [Scheme 1-2] [ka] where T 2 is a leaving group or metal group, and the other symbols are as defined above.

[0179] T 2 An example of a "leaving group" is T 1 These include those exemplified as "leaving groups" of the above. T 2 An example of a "metal group" is T 1 The "metal group" includes those exemplified above. Compounds (3'), (9) and (11) may be commercially available products or may be prepared by methods known per se.

[0180] X 1 is CR X1a and X 3 and X 4 is C and X 6 is CR X6 and X 2 and X 5 Compound (I) in which is N can be produced from compound (12) by the method shown in Scheme 1-3. [Scheme 1-3] [ka] where L 5 is a leaving group, and M 3 is a metal group, R X1a is a hydrogen atom or C 1-2 is an alkyl group, and R is C 1-2 is an alkyl group, and the other symbols are as defined above.

[0181] L 5 An example of a "leaving group" is L 1 ~L 4 These include those exemplified as "leaving groups" of the above. M 3 An example of a "metal group" is M 1 and M 2 The "metal group" includes those exemplified above. Compounds (2), (12), (13) and (16) may be commercially available products or can be prepared by methods known per se. Compound (5) can be prepared according to Scheme 1-1.

[0182] -VZ-ring B 1 is -O-CH(R 1 )-CH2-Ring B 2 Compound (2), which is compound (2'), can be produced from compound (19) by the method shown in Scheme 2-1 or a similar method known per se (WO2018 / 183112A1 and WO2020 / 068854A1). [Scheme 2-1] [ka] where L 6 is a leaving group, and the other symbols are as defined above.

[0183] L 6 An example of a "leaving group" is L 1 ~L 4 These include those exemplified as "leaving groups" of the above. Compounds (19), (20), (22) and (23) may be commercially available products or may be prepared by methods known per se.

[0184] The starting compound and / or intermediates for preparing Compound (I) may form salts. The salts are not particularly limited as long as the reaction can be carried out, but examples include salts similar to those optionally formed by Compound (I). When isomerization occurs, the configurational isomers (E, Z forms) of Compound (I) can be isolated and purified to obtain pure compounds, for example, by conventional separation means, such as extraction, recrystallization, distillation, chromatography, etc. Furthermore, the corresponding pure isomers can also be obtained by isomerizing the double bond using heating, an acid catalyst, a transition metal complex, a metal catalyst, a radical catalyst, light irradiation, a strong base catalyst, etc., according to the methods described in Shin Jikken Kagaku Koza 14 (edited by the Chemical Society of Japan), pp. 251-253, or 4th Edition Jikken Kagaku Koza 19 (edited by the Chemical Society of Japan), pp. 273-274, or methods similar thereto.

[0185] Compound (I) includes stereoisomers depending on the type of substituent, and each stereoisomer and mixtures thereof are included in the present invention. Compound (I) may be hydrated or non-hydrated. If desired, compound (I) can be synthesized by deprotection reaction, acylation reaction, alkylation reaction, hydrogenation reaction, oxidation reaction, reduction reaction, carbon chain elongation reaction, halogenation reaction, substituent exchange reaction, coupling reaction, reductive amination, nucleophilic addition reaction with a carbanion, Grignard reagent and deoxyfluorination reaction, either alone or in combination of two or more thereof. When the desired product is obtained in the free form by the above reaction, it can be converted into a salt by conventional methods, or when the desired product is obtained as a salt, it can be converted into the free form or another salt by conventional methods. Compound (I) thus obtained can be isolated and purified from the reaction mixture by known methods, such as phase transfer, concentration, solvent extraction, distillation, crystallization, recrystallization, chromatography, etc. When compound (I) contains configurational isomers, diastereomers, conformational isomers, etc., they can be isolated by the above-described separation and purification methods, if desired. Furthermore, when compound (I) is racemic, the d-form and l-form can be isolated by conventional optical resolution.

[0186] The compound (I), other reaction intermediates and the starting compounds thus obtained can be isolated and purified from the reaction mixture by methods known per se, such as extraction, concentration, neutralization, filtration, distillation, recrystallization, column chromatography, thin-layer chromatography, preparative high-performance liquid chromatography (preparative HPLC), medium-pressure preparative liquid chromatography (medium-pressure preparative LC), and the like.

[0187] Salts of compound (I) can be prepared by methods known per se, for example, by adding an inorganic or organic acid when compound (I) is a basic compound, or by adding an organic or inorganic base when compound (I) is an acidic compound. When compound (I) contains optical isomers, each optical isomer and a mixture thereof are included within the scope of the present invention, and these isomers can be subjected to optical resolution or individually produced by methods known per se, if desired. When compound (I) contains configurational isomers, diastereomers, conformational isomers, etc., each can be isolated by the above-mentioned separation and purification methods, if desired. Furthermore, when compound (I) is racemic, the S-form and R-form can be isolated by conventional optical resolution. When compound (I) includes stereoisomers, each isomer and mixtures thereof are included in the present invention.

[0188] Compound (I) may be a prodrug. A prodrug of compound (I) refers to a compound that is converted to compound (I) by a reaction with an enzyme, gastric acid, or the like under physiological conditions in a living body, i.e., a compound that is converted to compound (I) by oxidation, reduction, hydrolysis, or the like with an enzyme; or a compound that is converted to compound (I) by hydrolysis, such as with gastric acid.

[0189] Prodrugs of compound (I) include compounds obtained by acylation, alkylation, or phosphorylation of the amino group of compound (I) (for example, compounds obtained by eicosanoylation, alanylation, pentylaminocarbonylation, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxycarbonylation, tetrahydrofuranylation, pyrrolidylmethylation, pivaloyloxymethylation, or tert-butylation of the amino group of compound (I)); compounds obtained by acylation, alkylation, phosphorylation, or boronation of the hydroxy group of compound (I) (for example, acetylation, palmitoylation, propanoylation, pivaloylation, sucraloxymethylation, etc. of the hydroxy group of compound (I)). Compounds obtained by subjecting the carboxyl group of compound (I) to acylation, fumarylation, alanylation, dimethylaminomethylcarbonylation, or the like; compounds obtained by subjecting the carboxyl group of compound (I) to esterification or amidation (for example, compounds obtained by subjecting the carboxyl group of compound (I) to ethyl esterification, phenyl esterification, carboxymethyl esterification, dimethylaminomethyl esterification, pivaloyloxymethyl esterification, ethoxycarbonyloxyethyl esterification, phthalidyl esterification, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl esterification, cyclohexyloxycarbonylethyl esterification, methylamidation, or the like). Any of these compounds can be produced from compound (I) by a method known per se. A prodrug of compound (I) can be a compound that converts to compound (I) under physiological conditions as described in Development of Pharmaceuticals, Vol. 7, Molecular Design, pp. 163-198, Hirokawa Shoten (1990).

[0190] Compound (I) or a prodrug thereof (hereinafter referred to as the compound of the present invention) has excellent in vivo kinetics (e.g., plasma drug half-life, intracerebral mobility, metabolic stability) and low toxicity (e.g., liver / hepatotoxicity, acute toxicity, chronic toxicity, genotoxicity, reproductive toxicity, cardiotoxicity, cytotoxicity, drug interactions, carcinogenicity, etc.; particularly, it is superior as a pharmaceutical in terms of liver / hepatotoxicity). The compound of the present invention can be safely administered orally or parenterally to mammals (e.g., humans, monkeys, cows, horses, pigs, mice, rats, hamsters, rabbits, cats, dogs, sheep, and goats) and used directly as a pharmaceutical, or mixed with a pharmaceutically acceptable carrier or the like to form a pharmaceutical composition. Examples of "parenteral" administration include intravenous, intramuscular, subcutaneous, intraorgan, intranasal, intradermal, ocular, intracerebral, rectal, intravaginal, intraperitoneal, and intratumoral administration, administration near a tumor, and direct administration to a lesion.

[0191] The compounds of the present invention have excellent CaMKII inhibitory activity, and therefore, for example, in animals, particularly mammals (e.g., humans, monkeys, cats, pigs, horses, cows, mice, rats, guinea pigs, dogs, rabbits, etc.), Cardiac disease (cardiac hypertrophy, acute heart failure and congestive heart failure, cardiomyopathy, angina pectoris, myocarditis, atrial / ventricular arrhythmias, tachycardia, chronic heart failure including myocardial infarction, etc.), myocardial ischemia, venous insufficiency, progression to heart failure after myocardial infarction, hypertension, cor pulmonale, arteriosclerosis including atherosclerosis (aneurysm, coronary arteriosclerosis, cerebral arteriosclerosis, peripheral arteriosclerosis, etc.), post-interventional vascular thickening, vascular thickening / obstruction and organ damage (percutaneous coronary angioplasty, stent placement, coronary angioscopy, intravascular ultrasound, coronary thrombolytic therapy, etc.), vascular re-obstruction / restenosis after bypass surgery, cardiac dysfunction after cardiopulmonary bypass surgery, respiratory disease (common cold syndrome, pneumonia, asthma, pulmonary hypertension, pulmonary thrombosis / embolism, etc.), bone Disorders (non-metabolic bone disorders, such as fractures, re-fractures, bone deformities / spondylosis deformans, osteosarcoma, myeloma, dysostosis and scoliosis, bone defects, osteoporosis, osteomalacia, rickets, osteitis fibrosis, renal osteodystrophy, Paget's disease of bone, myelitis with stiffness, rheumatoid arthritis, joint tissue destruction in osteoarthritis of the knee and similar disorders), inflammatory diseases (diabetic complications, such as retinopathy, nephropathy, nerve damage, macroangiopathy, etc.; arthritis, such as rheumatoid arthritis, osteoarthritis, rheumatoid myelitis, periostitis, etc.; post-operative / traumatic inflammation; swelling reduction; pharyngitis; cystitis; pneumonia; atopic dermatitis; inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, etc.; meningitis; inflammatory eye diseases).Inflammatory lung diseases, such as pneumonia, silicosis, pulmonary sarcoidosis, pulmonary tuberculosis, etc.), allergic diseases (allergic rhinitis, conjunctivitis, gastrointestinal allergies, pollen allergies, anaphylaxis, etc.), drug addiction, neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, AIDS encephalopathy, etc.), central nervous system damage (disorders, such as cerebral hemorrhage and cerebral infarction and their sequelae and complications, head injury, spinal cord injury, cerebral edema, sensory dysfunction, paresthesia, autonomic dysfunction, abnormal autonomic nervous function, multiple sclerosis, etc.), dementia, memory confusion, confusion of consciousness, memory loss, anxiety symptoms, neurological symptoms, unpleasant states, mental disorders (depression, epilepsy, alcohol Prevention or treatment of ischemic peripheral circulatory disorders, deep vein thrombosis, obstructive peripheral circulatory disorders, arteriosclerosis obliterans (ASO), thromboangiitis obliterans, diabetes (type 1 diabetes, type 2 diabetes, gestational diabetes, etc.), diabetic complications (nerve damage, nephropathy, retinopathy, cataracts, macroangiopathy, osteopenia, diabetic hyperosmolar diabetic coma, infections, diabetic gangrene, dry mouth, hearing loss, cerebrovascular damage, peripheral circulatory disorders, etc.), urinary incontinence, metabolic / nutritional disorders (obesity, hyperlipidemia, hypercholesterolemia, diabetes, impaired glucose tolerance, hyperuricemia, hyperkalemia, hypernatremia, etc.), metabolic syndrome, visceral obesity syndrome, male or female sexual dysfunction, etc.; Taste disorders, olfactory disorders, blood pressure circadian rhythm abnormalities, cerebrovascular damage (asymptomatic cerebrovascular damage, transient ischemic attack, stroke, vascular dementia, hypertensive encephalopathy, cerebral infarction, etc.), cerebral edema, cerebral circulatory disorders, recurrence and sequelae of cerebrovascular damage (neurological symptoms, psychiatric symptoms, subjective symptoms, impairment of activities of daily living, etc.), kidney disease (nephritis, glomerulonephritis, glomerulosclerosis, renal failure, thrombotic microangiopathy, diabetic nephropathy, nephrotic syndrome, hypertensive nephrosclerosis, dialysis complications, organ damage including irradiation-induced nephropathy, etc.), post-transplant polycythemia / hypertension / organ damage / vascular hyperplasia, post-transplant rejection, eye disorders (glaucoma, ophthalmopathy) hypertension, etc.), thrombosis, multiple organ failure, endothelial dysfunction, hypertensive tinnitus, other circulatory diseases (ischemic cerebral circulatory disorders, Raynaud's disease, Buerger's disease, etc.), chronic obstructive pulmonary disease, interstitial pneumonia, Pneumocystis carinii pneumonia, connective tissue disorders (e.g., systemic lupus erythematosus, scleroderma, polyarteritis nodosa, etc.), liver disorders (hepatitis and cirrhosis, including chronic types), portal hypertension, digestive disorders (gastritis, gastric ulcer, gastric cancer, post-gastric surgery disorders, dyspepsia, esophageal ulcer, pancreatitis, colon polyps, gallstones, hemorrhoidal disease, ruptured esophageal and gastric varices, etc.), hematologic / hematopoietic disorders (polycythemia, angiopurpura, autoimmune hemolysis) anemia, disseminated intravascular coagulation syndrome, multiple myeloma, etc.), solid tumors, tumors (malignant melanoma, malignant lymphoma, digestive system (e.g., stomach, intestinal) cancer, etc.), cancer and associated cachexia, cancer metastasis, endocrine disorders (Addison's disease, Cushing's syndrome, pheochromocytoma, primary aldosteronism, etc.), Creutzfeldt-Jakob disease, urinary / male reproductive diseases (cystitis, prostatic hyperplasia, prostate cancer, sexually transmitted diseases, etc.), gynecological disorders (menopausal disorders, preeclampsia, endometriosis, uterine fibroids, ovarian diseases, breast diseases, sexually transmitted diseases, etc.), diseases caused by environmental / occupational factors (e.g., radiation damage, damage from ultraviolet / infrared / laser beams, altitude sickness, etc.), infectious diseases (e.g. viral infections with cytomegalovirus, influenza virus and herpes virus, rickettsial infections, bacterial infections, etc.), toxemia (sepsis, septic shock, endotoxic shock, gram-negative sepsis, toxic shock syndrome, etc.), ear, nose and throat diseases (Meniere's disease, tinnitus, taste disorders, vertigo, balance disorders, swallowing disorders, etc.), skin diseases (keloids, hemangiomas, psoriasis, etc.), dialysis (hypotension, myasthenia gravis, systemic diseases such as chronic fatigue syndrome, etc.),Prevention or treatment of heart diseases (especially catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmias), It is expected to be useful for Here, the concept of preventing heart disease includes prognostic treatment of myocardial infarction, angina attack, cardiac bypass surgery, thrombolytic therapy, coronary revascularization, etc., and the concept of treating heart disease includes suppressing the progression or severity of heart failure (including both systolic dysfunction HFrEF and heart failure HFpEF with preserved ejection fraction) and maintaining cardiac function when non-pharmacological treatments for severe heart failure / arrhythmia are performed (e.g., implantable cardioverter defibrillator, cardiac sympathectomy, catheter ablation, cardiac pacemaker, intra-aortic balloon pumping, ventricular assist device, Batista procedure, cell transplantation, gene therapy, heart transplantation, etc.). When the compound of the present invention is applied to the prevention or treatment of heart failure, it is expected that improvement in cardiac contractility or relaxation will be achieved with short-term administration without side effects such as decreased blood pressure, tachycardia, decreased renal blood flow, etc., regardless of differences in underlying diseases such as ischemic heart disease, cardiomyopathy, hypertension, etc. and symptoms such as systolic dysfunction, diastolic dysfunction, etc. Furthermore, in addition to short-term improvement in cardiac function, long-term improvement in prognosis (survival rate, rehospitalization rate, cardiac event rate, etc.) is expected. When the compound of the present invention is applied to the prevention or treatment of arrhythmia, regardless of etiology and atrial / ventricular differentiation, symptom improvement or remission is expected to be achieved. Furthermore, long-term improvement in prognosis (survival rate, rehospitalization rate, cardiac event rate, etc.) is expected to be achieved.

[0192] The dosage of the compound of the present invention varies depending on the administration route, symptoms, etc., but for example, when the compound is orally administered to a patient with heart disease (adult, body weight 40 to 80 kg, e.g., 60 kg), the dosage is, for example, 0.001 to 1000 mg / kg body weight / day, preferably 0.01 to 100 mg / kg body weight / day, more preferably 0.1 to 10 mg / kg body weight / day. This amount may be administered 1 to 3 times per day.

[0193] The medicament containing the compound of the present invention can be used alone or as a pharmaceutical composition containing the compound of the present invention and a pharmaceutically acceptable carrier, prepared by a method known per se as a manufacturing method for pharmaceutical preparations (for example, a method described in the Japanese Pharmacopoeia, etc.). The medicament containing the compound of the present invention can be prepared, for example, in the form of tablets (sugar-coated tablets, film-coated tablets, sublingual tablets, orally disintegrating tablets, buccal tablets, etc.), pills, powders, granules, capsules (including soft capsules and microcapsules), troches, syrups, liquids, emulsions, suspensions, controlled-release preparations (for example, immediate-release preparations, sustained-release preparations, sustained-release microcapsules), aerosols, films (for example, orally disintegrating films, oral mucoadhesive films, etc.).

[0049] They can be safely administered orally or parenterally (e.g., intravenous, intramuscular, subcutaneous, intravisceral, intranasal, intradermal, eye drop, intracerebral, rectal, vaginal, intraperitoneal administration and administration to a lesion) in the form of a drug, a drug film, an injection (e.g., subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection), a drip infusion, a transdermal preparation, an ointment, a lotion, an adhesive preparation, a suppository (e.g., rectal suppository, vaginal suppository), a pellet, a nasal preparation, a pulmonary preparation (inhalant), an eye drop, or the like.

[0194] As mentioned above in the "pharmaceutically acceptable carrier," various organic or inorganic carriers commonly used as formulation materials (starting materials) can be used. For example, additives, lubricants, binders, disintegrants, etc. are used for solid formulations, while solvents, solubilizers, suspending agents, isotonicity agents, buffers, sedatives, etc. are used for liquid formulations. If necessary, formulation additives such as preservatives, antioxidants, coloring agents, sweeteners, etc. can also be used. Examples of additives include lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, light anhydrous silicic acid, and the like. Examples of lubricants include magnesium stearate, calcium stearate, talc, colloidal silica, and the like. Examples of binders include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, starch, sucrose, gelatin, methyl cellulose, sodium carboxymethyl cellulose, and the like. Examples of disintegrants include starch, carboxymethylcellulose, carboxymethylcellulose calcium, sodium carboxymethylstarch, L-hydroxypropylcellulose, and the like. Examples of solvents include water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, olive oil, etc. Examples of solubilizing agents include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, etc. Examples of suspending agents include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glycerin monostearate, etc.; hydrophilic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc. Examples of isotonic agents include glucose, D-sorbitol, sodium chloride, glycerin, D-mannitol, and the like. Examples of buffering agents include buffer solutions such as phosphate, acetate, carbonate, citrate, and the like. Examples of sedatives include benzyl alcohol and the like. Examples of preservatives include p-oxybenzoate, chlorobutanol, benzyl alcohol, phenylethyl alcohol, dehydroacetic acid, sorbic acid, and the like. Examples of antioxidants include sulfite, ascorbic acid, α-tocopherol, and the like.

[0195] Pharmaceutical compositions vary depending on the dosage form, administration method, carrier, etc., but can be prepared by conventional methods by adding the compound of the present invention in a proportion of generally 0.01 to 100% (w / w), preferably 0.1 to 95% (w / w), of the total amount of the formulation.

[0196] When the compound of the present invention is applied to each of the above diseases, it can be used in appropriate combination with drugs (hereinafter abbreviated as concomitant drugs) or treatment methods generally used for such diseases. For heart failure, for example, angiotensin converting enzyme (ACE) inhibitors (e.g., alacepril, captopril, cilazapril, delapril, enalapril, lisinopril, temocapril, trandolapril, quinapril, imidapril, benazepril, perindopril, etc.), angiotensin II receptor antagonists (e.g., losartan, candesartan cilexetil, valsartan, telmisartan, irbesartan, forasartan, etc.), angiotensin II receptor antagonists / NEP inhibitors combination drugs (Entresto), beta-receptor antagonists (e.g., propranolol, nadolol, timolol, nipradilol, bunitrolol, indenolol, penbutolol, carteolol, carvedilol, pindolol, acebutolol, atenolol, bisoprolol, metoprolol, labetalol, amosulalol, arotinolol, etc.), calcium antagonists (e.g., manidipine, nicardipine, nilvadipine, nisoldipine, nitrendipine, benidipine, amlodipine, aranidipine, etc.), diuretics (e.g., thiazide diuretics, such as benzylhydrochlorothiazide, cyclopenthiazide, ethiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, penfluthiazide, polythiazide, trichloramethiazide, etc.; loop diuretics, such as chlorthalidone, clofenamide, indapamide, mefruside, meticrane, sotolazone, trivamide, quinethazone, metolazone, furosemide, mefruside, etc.; potassium-sparing diuretics, such as spironolactone, triamterene, etc. ), digitalis preparations (e.g., digitoxin, digoxin, methyldigoxin, lanatoside C, proscillaridin, etc.), ANP or BNP preparations, calcium sensitizers (e.g., pimobendan, etc.), anticoagulants (e.g., warfarin, sodium citrate, activated protein C, tissue factor pathway inhibitor, antithrombin III, dalteparin sodium, aragatroban, gabexate, ozagrel sodium, ethyl icosapentate, beraprost sodium, alprostadil, pentoxifylline, tisokinase,streptokinase, etc.), antiarrhythmic drugs (e.g., sodium channel blockers, such as quinidine, procainamide, disopyramide, ajmaline, cibenzoline, lidocaine, diphenylhydantoin, mexiletine, propafenone, flecainide, pilsicainide, phenytoin, etc.; potassium channel blockers, such as amiodarone, etc.; calcium channel blockers, such as verapamil, diltiazem, etc.), PDE inhibitors (e.g., amrinone, milrinone, olprinone hydrochloride, etc.), diabetes treatment drugs (e.g., sulfonylureas, such as tolbutamide, chlorpropamide, glycopyramide, acetohexamide, tolazamide, glucagon-like peptide-1 (GPE), thiazolinone, ... It can be used simultaneously with ribenclamide, glybuzole, etc.; biguanides, for example, metformin hydrochloride, buformin hydrochloride, etc.; α-glucosidase inhibitors, for example, voglibose, acarbose, etc., insulin sensitizers, for example, pioglitazone, troglitazone, etc.; SGLT2 inhibitors, for example, ipragliflozin, dapagliflozin, luseogliflozin, tofogliflozin, canagliflozin, empagliflozin, etc.; insulin, glucagon; drugs for treating diabetic complications (for example, epalrestat, etc.), anti-obesity drugs, etc., and can also be used during the implementation of an implantable artificial heart, an implantable cardioverter defibrillator, ventricular pacing, Batista surgery, heart transplantation, or cell transplantation. Furthermore, for arrhythmias, for example, other antiarrhythmic drugs (e.g., sodium channel blockers, e.g., flecainide, quinidine, procainamide, disopyramide, ajmaline, cibenzoline, lidocaine, diphenylhydantoin, mexiletine, propafenone, pilsicainide, phenytoin, etc.; potassium channel blockers, e.g., amiodarone, etc.; calcium channel blockers, e.g., verapamil, diltiazem, etc.) and beta-receptor antagonists, non-drug treatments (e.g., implantable cardioverter defibrillators, cardiac sympathectomy, catheter ablation, cardiac pacemakers, etc.). Furthermore, after acute myocardial infarction or during the prognosis of myocardial infarction, for example, the compounds can be used in combination with antithrombotic agents (e.g., anticoagulants, e.g., heparin sodium, heparin calcium, warfarin, etc.; thrombolytic agents, e.g., urokinase, etc.; antiplatelet drugs, e.g., aspirin, sulfinpyrazone (anturane), dipyridamole (persantin),It can be used in combination with ticlopidine (Panaldin), cilostazol (Pletal), clopidogrel, etc.), angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, β-receptor antagonists, drugs for treating diabetes, drugs for treating hyperlipidemia (e.g., HMG-CoA reductase inhibitors, such as pravastatin, fluvastatin, cerivastatin, atorvastatin, etc.; fibrate drugs, such as simfibrate, clofibrate aluminum, clinofibrate, fenofibrate, etc.), coronary vascular reconstruction surgery, such as PTCA, CABG, etc. Additionally, in rheumatoid arthritis, for example, the compounds can be used in combination with nonsteroidal anti-inflammatory drugs (e.g., acetaminophen, phenacetin, ethenzamide, sulpyrine, antipyrine, migrenin, aspirin, mefenamic acid, flufenamic acid, diclofenac sodium, loxoprofen sodium, phenylbutazone, indomethacin, ibuprofen, ketoprofen, naproxen, oxaprozin, flurbiprofen, fenbufen, pranoprofen, floctafenine, epirizole, tiaramide hydrochloride, zaltoprofen, gabexate mesilate, camostat mesilate, urinastatin, colchicine, probenecid, sulfinpyrazone, benzbromarone, allopurinol, sodium gold thiomalate, sodium hyaluronate, sodium salicylate, morphine hydrochloride, salicylic acid, atropine, scopolamine, morphine, pethidine, levorphanol, ketoprofen, naproxen, oxymorphone or a salt thereof, etc.), immunomodulators or immunosuppressants (e.g., methotrexate, cyclosporine, tacrolimus, gusperimus, azathioprine, antilymphocyte serum, dried sulfonated immunoglobulin, erythropoietin, colony-stimulating factors, interleukins, interferons, etc.), steroids (e.g., dexamethasone, hexestrol, methimazole, betamethasone, triamcinolone, triamcinolone acetonide, fluocinonide, fluocinolone acetonide, prednisolone, methylprednisolone, cortisone acetate, hydrocortisone, fluorometholone, beclomethasone dipropionate, estriol, etc.), p38 MAP kinase inhibitors, anti-TNF-α drugs (e.g., etanercept,It can be used in combination with infliximab, D2E7, CDP-571, PASS TNF-α, soluble TNF-α receptor, TNF-α binding protein, anti-TNF-α antibody, etc.), cyclooxygenase inhibitors (e.g., salicylic acid derivatives such as celecoxib, rofecoxib, aspirin, MK-663, valdecoxib, SC-57666, tiracoxib, S-2474, diclofenac, indomethacin, loxoprofen, etc.), etc. Furthermore, when the compounds of the present invention are applied to the above-mentioned diseases, they can be used in combination with biological preparations (e.g., antibodies, vaccine preparations, etc.), and the compounds can also be combined with gene therapy or other combination therapies. Examples of antibody and vaccine preparations include angiotensin II vaccine preparations, CETP vaccine preparations, CETP antibodies, TNFα antibodies, antibodies against other cytokines, amyloid-β vaccine preparations, type 1 diabetes vaccines (e.g., DIAPEP-277 from Peptor Ltd.), anti-HIV antibodies, HIV vaccine preparations, antibodies and vaccine preparations against cytokines, renin-angiotensin enzymes and their products, vaccine preparations against enzymes and proteins involved in blood lipid metabolism, vaccine preparations against enzymes and proteins involved in the coagulation and fibrinolysis system, and antibodies and vaccine preparations against proteins involved in glucose metabolism and insulin resistance. Furthermore, combination with biological preparations involving growth factors, such as GH and IGF, is possible. Examples of gene therapy include treatment methods using genes related to cytokines, renin-angiotensin enzymes and their products, G proteins, G protein-coupled receptors and their phosphorylating enzymes, DNA decoys, such as NFκB decoys, antisense therapies, genes related to enzymes and proteins involved in blood lipid metabolism (e.g., genes involved in the metabolism, excretion, and absorption of cholesterol, triglycerides, HDL-cholesterol, blood phospholipids, etc.), genes related to enzymes and proteins involved in angiogenesis therapy (e.g., growth factors such as HGF, VEGF, etc.) for the purpose of peripheral vascular occlusion, etc., genes related to proteins involved in glucose metabolism and insulin resistance, and antisense therapies against cytokines, such as TNF-α. Furthermore, the compounds can be used in combination with cell transplantation therapies using bone marrow cells (bone marrow mononuclear cells, bone marrow mesenchymal stem cells, etc.) and artificial organs (artificial blood vessels and cardiac muscle cell sheets) using tissue engineering for various organ regeneration methods, such as heart regeneration, kidney regeneration, pancreatic regeneration, and vascular regeneration.

[0197] By combining the compound of the present invention with a concomitant drug, excellent effects can be achieved, for example, (1) The dosage can be reduced compared to administration of the compound of the present invention or a combination drug alone; (2) The drug to be combined with the compound of the present invention can be selected depending on the patient's condition (mild case, severe case, etc.). (3) The treatment period can be extended by selecting a concomitant drug having an action and mechanism different from that of the compound of the present invention. (4) A sustained therapeutic effect can be designed by selecting a concomitant drug having an action and mechanism different from that of the compound of the present invention. (5) Synergistic effects may be provided by the combined use of the compound of the present invention and a concomitant drug.

[0198] Hereinafter, the compound of the present invention and the concomitant drug used in combination will be referred to as the "combination of the present invention." When using the combination of the present invention, the administration time of the compound of the present invention and the concomitant drug is not limited, and the compound of the present invention or a pharmaceutical composition thereof and the concomitant drug or a pharmaceutical composition thereof can be administered to a subject simultaneously or at different times. The dosage of the concomitant drug can be determined according to the dosage used clinically and can be appropriately selected depending on the administration subject, administration route, disease, combination, etc. The administration method of the concomitant drug of the present invention is not particularly limited, and it is sufficient that the compound of the present invention and the concomitant drug are administered in combination. Examples of such administration methods include the following methods: (1) Administration of a single preparation obtained by simultaneous processing of the compound of the present invention and the concomitant drug; (2) Simultaneous administration of two preparations of the compound of the present invention and the concomitant drug, which are separately manufactured, by the same administration route; (3) Administration of two preparations of the compound of the present invention and the concomitant drug, which are separately manufactured, at different times by the same administration route; (4) Simultaneous administration of two preparations of the compound of the present invention and the concomitant drug, which are separately manufactured, by different administration routes; (5) Administration of two preparations of the compound of the present invention and the concomitant drug, which are separately manufactured, at different times by different administration routes (e.g., administration of the compound of the present invention and the concomitant drug in the order or in the reverse order), etc.

[0199] The combination of the present invention exhibits low toxicity. For example, the compound of the present invention and / or the above-mentioned combination drug can be combined with a pharmacologically acceptable carrier according to known methods for preparing pharmaceutical compositions to prepare, for example, tablets (including sugar-coated tablets and film-coated tablets), powders, granules, capsules (including soft capsules), liquids, injections, suppositories, sustained-release preparations, etc. These compositions can be safely administered orally or parenterally (for example, topically, rectally, intravenously, etc.). Injections can be administered intravenously, intramuscularly, subcutaneously, or intraorganically, or directly into the lesion. Examples of pharmacologically acceptable carriers useful for preparing the combination of the present invention include various organic or inorganic carrier substances commonly used as pharmaceutical materials.For solid preparations, for example, additives, lubricants, binders and disintegrants can be used.For liquid preparations, for example, solvents, solubilizers, suspending agents, isotonicity agents, buffers, sedatives, etc. can be used.If necessary, appropriate amounts of conventional preservatives, antioxidants, coloring agents, sweeteners, adsorbents, wetting agents, etc. can be used as appropriate. Examples of additives include lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, light anhydrous silicic acid, and the like. Examples of lubricants include magnesium stearate, calcium stearate, talc, colloidal silica, and the like. Examples of binders include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, starch, sucrose, gelatin, methyl cellulose, sodium carboxymethyl cellulose, and the like. Examples of disintegrants include starch, carboxymethylcellulose, carboxymethylcellulose calcium, sodium carboxymethylstarch, L-hydroxypropylcellulose, and the like. Examples of solvents include water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, olive oil, etc. Examples of solubilizing agents include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, and the like. Examples of suspending agents include surfactants such as stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glycerin monostearate, etc.; hydrophilic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc.

[0200] Examples of isotonic agents include glucose, D-sorbitol, sodium chloride, glycerin, D-mannitol, and the like. Examples of buffering agents include buffer solutions such as phosphate, acetate, carbonate, citrate, and the like. Examples of sedatives include benzyl alcohol and the like. Examples of preservatives include p-oxybenzoate, chlorobutanol, benzyl alcohol, phenylethyl alcohol, dehydroacetic acid, sorbic acid, and the like. Examples of antioxidants include sulfite, ascorbic acid, α-tocopherol, and the like.

[0201] The mixing ratio of the compound of the present invention to the concomitant drug in the combination agent of the present invention can be appropriately selected depending on the subject of administration, the administration route, the disease, and the like. For example, the content of the compound of the present invention in the combination agent of the present invention varies depending on the form of the formulation, and is usually about 0.01 to about 100 wt%, preferably about 0.1 to about 50 wt%, and more preferably about 0.5 to about 20 wt%, based on the formulation. The content of the concomitant drug in the combination agent of the present invention varies depending on the form of the preparation, and is usually about 0.01 to about 100 wt%, preferably about 0.1 to about 50 wt%, more preferably about 0.5 to about 20 wt%, based on the preparation. The content of additives, such as carriers, in the combination of the present invention varies depending on the form of the preparation, and is usually about 1 to about 99.99 wt %, preferably about 10 to about 90 wt %, based on the preparation. When the compound of the present invention and the concomitant drug are separately formulated into a preparation, the contents thereof are similar to those described above. [Example]

[0202] The present invention will now be described in detail with reference to examples, experimental examples and formulation examples, which should not be construed as limiting, and the present invention may be modified within the scope of the present invention. In the following examples, "room temperature" generally means about 10°C to about 35°C. Ratios of solvent mixtures are volumetric mixing ratios unless otherwise specified. % means wt% unless otherwise specified. Unless otherwise specified, the elution of column chromatography in the examples was carried out under observation by TLC (thin layer chromatography). 254The TLC plate was used, and the solvent used as the elution solvent for column chromatography was used as the developing solvent. A UV detector was used for detection. In silica gel column chromatography, NH refers to aminopropylsilane-bonded silica gel, and diol refers to the use of 3-(2,3-dihydroxypropoxy)propylsilane-bonded silica gel. In preparative HPLC (high-performance liquid chromatography), C18 refers to the use of octadecyl-bonded silica gel. The ratios of elution solvents are volumetric mixture ratios unless otherwise specified. 1 For H NMR analysis, ACD / SpecManager (trade name) software was used. Peaks for hydroxyl groups, amino groups, etc., which have extremely weak protons, may not be recorded. MS was measured by LC / MS. ESI or APCI was used as the ionization method. The data represent actual measurements (actual values). Generally, a molecular ion peak is observed, and fragment ions may be observed. In the case of salts, the molecular ion peak or fragment ion peak of the free form is generally observed. Optical rotation ([α] D The sample concentration (c) for is in g / 100 mL. Elemental analysis values ​​(Anal.) are reported as calculated values ​​(Calcd) and actual measured values ​​(Meas.). In the examples, the peaks measured by powder X-ray diffraction are those measured at room temperature using Cu Kα radiation as a supply voltage with an Ultima IV (Rigaku Corporation, Japan). The measurement conditions are as follows: Voltage / Current: 40kV / 50mA Scanning speed: 6 degrees / min 2 Theta Scan Range: 2~35 degrees In the examples, the crystallinity determined by powder X-ray diffraction was calculated by the Hellman method. In the examples, the following abbreviations are used: mp: melting point M: Mass spectrum M: Molar concentration N: Regulation CDCl3: Deuterochloroform DMSO-d6: Deuterodimethyl sulfoxide CD3OD: Deuteromethanol 1 H NMR: proton nuclear magnetic resonance LC / M: Liquid chromatograph mass spectrometer TLC: Thin Layer Chromatography ESI: Electrospray ionization, electron spray ionization APCI: atmospheric pressure chemical ionization AcOH: acetic acid Boc: tert-butoxycarbonyl (Boc)2O: di-tert-butyl dicarbonate (Bpin)2: Bis(pinacolato)diboron br:Wide singlet n-BuOH: normal butanol n-BuLi: normal butyl lithium tBuXPho: 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl cataCXium (登録商標) A: Di(1-adamantyl)-n-butylphosphine Cu(OAc)2: Copper(II) acetate d: doublet dd: double doublet ddd: double double doublet dt: double triplet DCM: dichloromethane DEAD: Diethyl azodicarboxylate Deoxo-Fluor (登録商標) :Bis(2-methoxyethyl)aminosulfur trifluoride DIAD: Diisopropyl azodicarboxylate DIPEA: N,N-diisopropylethylamine DMA: N,N-dimethylacetamide DMAP: 4-dimethylaminopyridine DMF: N,N-dimethylformamide DME: 1,2-dimethoxyethane DMSO: dimethyl sulfoxide Et2O: Diethyl ether EtOAc: ethyl acetate EtOH: ethanol FA: Formic acid HOBt-H2O: 1-hydroxybenzotriazole monohydrate IPE: Diisopropyl ether KOAc: Potassium acetate m: multiplet mCPBA: 3-chlorobenzene-1-peroxycarboxylic acid MeOH: Methanol MsCl: methanesulfonyl chloride NaOMe: sodium methoxide NB: N-bromosuccinimide NMP: N-methylpyrrolidone Pd(OAc)2: Palladium(II) acetate Pd(amphos)Cl2: Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) Pd( t Bu3P)2: Bis(tri-tert-butylphosphine)palladium(0) Pd2(dba)3: Tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)Cl2: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd(PPh3)4: Tetrakis(triphenylphosphine)palladium(0) Pd(PPh3)2Cl2: Bis(triphenylphosphine)palladium(II) dichloride PE: Petroleum ether PPh3: Triphenylphosphine q: quartet s: singlet SEMCl: 2-(chloromethoxy)ethyltrimethylsilane t: triplet TBAF: Tetrabutylammonium fluoride TBSCl: tert-butyldimethylchlorosilane TEA: Triethylamine TFA: Trifluoroacetic acid TFE: 2,2,2-trifluoroethanol THF: tetrahydrofuran TMSCl: chlorotrimethylsilane TsCl: p-toluenesulfonyl chloride TsOH-H2O: p-toluenesulfonic acid monohydrate WSC-HCl: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

[0203] Example 1 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-[2-(diethylamino)ethyl]benzamide

[0204] A) Methyl (2S)-2-(5-bromo-2-cyanophenoxy)propanoate To a mixture of 4-bromo-2-hydroxybenzonitrile (14.5 g), methyl (2R)-2-hydroxypropanoate (15.3 g), PPh3 (57.6 g), and THF (150 mL) was added 2.2 M DEAD toluene solution (120 mL) at 0 °C. The mixture was stirred overnight at room temperature under a nitrogen atmosphere. The mixture was diluted with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / hexane) to give the title compound (20.0 g). 1H NMR (300 MHz, DMSO-d6) δ 7.72 (d, J = 8.3 Hz, 1H), 7.47 (d, J = 1.6 Hz, 1H), 7.35 (dd, J = 8.3, 1.7 Hz, 1H), 5.40 (q, J = 6.8 Hz, 1H), 3.71 (s, 3H), 1.57 (d, J = 6.8 Hz, 3H)

[0205] B) 4-Bromo-2-(((2S)-1-hydroxypropan-2-yl)oxy)benzonitrile To a mixture of methyl (2S)-2-(5-bromo-2-cyanophenoxy)propanoate (72.0 g) in MeOH (200 mL) and THF (100 mL) was added NaBH (4.76 g) at 0° C. The mixture was stirred at room temperature under a nitrogen atmosphere for 10 hours. The mixture was quenched with saturated aqueous NH Cl at 0° C. and concentrated under reduced pressure. The residue was extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / hexane) to give the title compound (65.0 g). 1 H NMR (300 MHz, DMSO-d6) δ 7.66 (d, J = 8.3 Hz, 1H), 7.60 (S, 1H), 7.28 (d, J = 8.3 Hz, 1H), 4.97 (t, J = 5.5 Hz, 1H), 4.65-4.78 (m, 1H), 3.54 (t, J = 5.4 Hz, 2H), 1.24 (d, J = 6.1 Hz, 3H)

[0206] C) (2S)-2-(5-bromo-2-cyanophenoxy)propyl methanesulfonate To a solution of 4-bromo-2-(((2S)-1-hydroxypropan-2-yl)oxy)benzonitrile (21.0 g) and TEA (23 mL) in THF (100 mL) was added MsCl (8.9 mL) at 0° C. The mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. The mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was filtered through a pad of NH silica gel and concentrated under reduced pressure to give the title compound (26.0 g). 1 H NMR (300 MHz, DMSO-d6) δ 7.70 (d, J = 8.3 Hz, 1H), 7.66 (d, J = 1.6 Hz, 1H), 7.34 (dd, J = 8.3, 1.7 Hz, 1H), 5.07 (td, J = 6.2, 3.0 Hz, m / z 335.2 [M+H] +

[0207] D) 4-Bromo-2-(((2S)-1-(1H-tetrazol-1-yl)propan-2-yl)oxy)benzonitrile To a mixture of (2S)-2-(5-bromo-2-cyanophenoxy)propyl methanesulfonate (25.0 g), 1H-tetrazole (10.5 g), and DMF (100 mL) was added K2CO3 (20.7 g) at room temperature, and the mixture was stirred at 80 °C overnight. The mixture was diluted with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / hexane) to give the title compound (10.3 g). 1H NMR (300 MHz, CDCl3) δ 8.88-9.02 (m, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.21 (dd, J = 8.3, 1.7 Hz, 1H), 7.01 (d, J = 1.6 Hz, 1H), 4.79-4.89 (m, 2H), 4.64-4.77 (m, 1H), 1.44-1.51 (m, 3H); MS m / z 308.2 [M+H] +

[0208] E) 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(((2S)-1-(1H-tetrazol-1-yl)propan-2-yl)oxy)benzonitrile To a mixture of 4-bromo-2-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}benzonitrile (5.00 g), (Bpin) (4.52 g), KOAc (7.93 g), and DMF (50 mL) was added Pd(dppf)Cl-CHCl (594 mg). After stirring at 100 °C for 4 h under a nitrogen atmosphere, the mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / hexane) to give the title compound (3.30 g). MS m / z 356.2 [M+H] +

[0209] F) 4-{pyrazolo[1,5-a]pyrimidin-5-yl}-2-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}benzonitrile To a solution of 5-chloropyrazolo[1,5-a]pyrimidine (120 mg), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}benzonitrile (666 mg) and Cs2CO3 (508 mg) in THF (10 mL) and water (2.0 mL) was added Pd( tBu3P2 (39.9 mg) was added, and the mixture was stirred at 70 °C under a nitrogen atmosphere for 10 hours. The mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH, EtOAc / hexane) to give the title compound (80.0 mg). 1 H NMR (300 MHz, DMSO-d6) δ 9.38 (s, 1H), 9.31 (d, J = 7.4 Hz, 1H), 8.31 (s, 1H), 7.85-7.97 (m, 3H), 7.80 (d, J = 7.2 Hz, 1H), 6.85 (s, MS m / z 347.2 [M+H] +

[0210] G) 4-{3-bromopyrazolo[1,5-a]pyrimidin-5-yl}-2-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}benzonitrile To a mixture of 4-{pyrazolo[1,5-a]pyrimidin-5-yl}-2-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}benzonitrile (180 mg) in DMF (5.0 mL) was added NBS (101 mg) at 0° C. The mixture was stirred at room temperature under a nitrogen atmosphere for 10 hours. The mixture was quenched with saturated aqueous NaHCO at 0° C. and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO, and concentrated under reduced pressure to give the crude title compound. The crude product was used in the next step without further purification. MS m / z 425.0 [M+H] +

[0211] H) Methyl 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidin-3-yl]benzoate A mixture of 4-{3-bromopyrazolo[1,5-a]pyrimidin-5-yl}-2-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}benzonitrile (220 mg) and [3-(methoxycarbonyl)phenyl]boronic acid (111 mg) in THF (20 mL) and water (4.0 mL) was treated with Cs2CO3 (252 mg) and Pd( t Bu3P2 (26.4 mg) was added, and the mixture was stirred at 80 °C under a nitrogen atmosphere for 14 hours. The mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH, EtOAc / hexane) to give the title compound (160 mg). 1 H NMR (300 MHz, DMSO-d6) δ 9.36-9.40 (m, 2H), 9.10 (s, 1H), 8.96 (s, 1H), 8.43 (d, J = 8.3 Hz, 1H), 8.05-8.14 (m, 2H), 7.84-8.02 (m, MS m / z 481.2 [M+H] +

[0212] I) 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidin-3-yl]benzoic acid To a mixture of methyl 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidin-3-yl]benzoate (150 mg) in MeOH (10 mL) and THF (10 mL) was added 2 M aqueous NaOH solution (0.16 mL). The mixture was stirred at 50° C. under a nitrogen atmosphere for 10 hours. The mixture was acidified (pH 2-3) with 6 M aqueous HCl solution. The precipitate was collected by filtration and dried under reduced pressure to give the crude title compound. The crude product was used in the next step without further purification. MS m / z 467.2 [M+H] +

[0213] J) 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-[2-(diethylamino)ethyl]benzamide To a mixture of 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidin-3-yl]benzoic acid (145 mg), WSC-HCl (178 mg), and HOBt-HO (125 mg) in DMF (5.0 mL) was added (2-aminoethyl)diethylamine (72.2 mg) and TEA (0.13 mL). The mixture was stirred under a nitrogen atmosphere for 16 h. The mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH, EtOAc / hexane) followed by preparative HPLC (0.1% TFA in water / CHCN). The desired fraction was azeotroped with toluene under reduced pressure. The residue was dissolved in MeOH (5.0 mL) and (登録商標) A21 was added to the mixture. The mixture was stirred at room temperature for 15 minutes, and then the insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure to give the title compound (15.0 mg) as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 9.34-9.40 (m, 2H), 8.91 (s, 1H), 8.87 (s, 1H), 8.46-8.53 (m, 1H), 8.35 (d, J = 7.0 Hz, 1H), 8.15 (s, 1H), 8.03-8.08 (m, 1H), 7.87-7.98 (m, 2H), 7.74 (d, J = 7.3 Hz, 1H), 7.55-7.62 (m, 1H), 5.52-5.65 (m, 1H), 4.87-5.06 (m, 2H), 3.33-3.46 (m, 4H), 2.52-2.67 (m, 4H), 1.43 (d, J = 5.8 Hz, 3H), 0.98 (t, J = 5.8 Hz, 6H); MS m / z 565.4 [M+H] +

[0214] Example 57 1-[(2S)-2-{2-fluoro-5-[2-methyl-3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propyl]-1H-tetrazole

[0215] A) Methyl (2S)-2-(5-bromo-2-fluorophenoxy)propanoate To a solution of 5-bromo-2-fluorophenol (74.0 g), methyl (2R)-2-hydroxypropanoate (80.7 g), and PPh3 (152 g) in THF (1000 mL) was added DIAD (118 g) portionwise at 0 °C. The mixture was stirred at 25 °C under a nitrogen atmosphere for 12 hours. The mixture was diluted with water (1000 mL) and extracted with EtOAc (800 mL × 3). The combined organic layer was washed with brine (1000 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (85.0 g). 1H NMR (400 MHz, CDCl3) δ 6.93-7.07 (m, 3H), 4.76 (q, J = 7.2 Hz, 1H), 3.77 (s, 3H), 1.65 (d, J = 6.8 Hz, 3H)

[0216] B) (2S)-2-(5-bromo-2-fluorophenoxy)propan-1-ol To a solution of methyl (2S)-2-(5-bromo-2-fluorophenoxy)propanoate (85.0 g) in THF (330 mL) and MeOH (660 mL) was added NaBH (17.4 g) portionwise over 0.5 h at 0 °C. The mixture was stirred at 25 °C for 12 h under a nitrogen atmosphere. The mixture was diluted with saturated aqueous NH Cl (500 mL) and water (500 mL) at 0 °C. The organic solvent was removed under reduced pressure. The residue was extracted with EtOAc (400 mL × 3). The combined organic layers were washed with brine (800 mL), dried over Na SO , and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (75.0 g). 1 H NMR (400 MHz, CDCl3) δ 7.16 (dd, J = 7.2, 2.0 Hz, 1H), 7.04-7.10 (m, 1H), 6.92-6.97 (m, 1H), 4.42-4.46 (m, 1H), 3.74-3.80 (m, 2H), 2.58 (brs, 1H), 1.29 (d, J = 6.0 Hz, 3H)

[0217] C) (2S)-2-(5-bromo-2-fluorophenoxy)propyl methanesulfonate To a solution of (2S)-2-(5-bromo-2-fluorophenoxy)propan-1-ol (75.0 g) and TEA (60.9 g) in THF (1000 mL) was added MsCl (48.3 g) dropwise at 0° C. The mixture was stirred at 25° C. under a nitrogen atmosphere for 1 hour. The mixture was diluted with water (800 mL) and extracted with EtOAc (1000 mL×3). The combined organic layer was washed with brine (800 mL), dried over Na2SO4, and concentrated under reduced pressure to give the title compound (97.0 g). 1 H NMR (400 MHz, CDCl3) δ 7.15 (dd, J = 7.2, 2.4 Hz, 1H), 7.06-7.10 (m, 1H), 6.94-6.99 (m, 1H), 4.59-4.63 (m, 1H), 4.35-4.36 (m, 2H), 3.05 (s, 3H), 1.38 (d, J = 6.4 Hz, 3H)

[0218] D) 1-[(2S)-2-(5-bromo-2-fluorophenoxy)propyl]-1H-tetrazole To a mixture of (2S)-2-(5-bromo-2-fluorophenoxy)propyl methanesulfonate (97.0 g) and 1H-tetrazole (41.5 g) in DMF (1000 mL) was added K2CO3 (82.0 g). The mixture was stirred at 80 °C for 12 hours. The mixture was diluted with saturated aqueous NH4Cl (600 mL) and extracted with EtOAc (200 mL × 3). The combined organic layers were washed with brine (600 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (31.0 g). 1 H NMR (400 MHz, CDCl3) δ 8.80 (s, 1H), 7.05-7.17 (m, 1H), 6.90-7.04 (m, 2H), 4.75-4.85 (m, 1H), 4.65-4.74 (m, 1H), 4.54-4.64 (m, 1H), 1.38 (d, J = 6.4 Hz, 3H)

[0219] E) 1-[(2S)-2-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propyl]-1H-tetrazole A mixture of 1-[(2S)-2-(5-bromo-2-fluorophenoxy)propyl]-1H-tetrazole (29.3 g), (Bpin) (37.1 g), Pd(dppf)Cl-CHCl (7.95 g), and KOAc (19.1 g) in DMSO (300 mL) was stirred at 100 °C for 2 h under a nitrogen atmosphere. The mixture was diluted with water (300 mL) and extracted with EtOAc (300 mL × 3). The combined organic layers were washed with brine (300 mL), dried over NaSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (33.0 g). 1 H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.33-7.35 (m, 1H), 7.26-7.29 (m, 1H), 6.94-6.99 (m, 1H), 4.89-4.93 (m, 2H), 4.70-4.76 (m, 1H), 1.35 (d, J = 5.2 Hz, 3H), 1.27 (s, 12H)

[0220] F) 1-[(2S)-2-(2-fluoro-5-{2-methylpyrazolo[1,5-a]pyrimidin-5-yl}phenoxy)propyl]-1H-tetrazole The reaction and purification were carried out according to Example 1, Step F to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.87 (s, 1H), 8.59 (d, J = 7.3 Hz, 1H), 7.72 (dd, J = 2.2, 8.0 Hz, 1H), 7.61 (ddd, J = 2.2, 4.4, 8.5 Hz, 1H), 7.20 (dd, J = 8.5, 10.5 Hz, 1H), 7.08 (d, J = 7.3 Hz, 1H), 6.48 (s, 1H), 4.87-4.95 (m, 1H), 4.80-4.86 (m, 1H), 4.65-4.73 (m, 1H), 2.53 (s, 3H), 1.45 (d, J = 6.2 Hz, 3H); MS m / z 354.3 [M+H] +

[0221] G) 1-[(2S)-2-(5-{3-bromo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl}-2-fluorophenoxy)propyl]-1H-tetrazole The reaction and purification were carried out according to Example 1, Step G to give the title compound. 1 H NMR (300 MHz, CDCl3) δ 8.88 (s, 1H), 8.56 (d, J = 7.3 Hz, 1H), 7.77 (dd, J = 2.2, 7.9 Hz, 1H), 7.69 (ddd, J = 2.2, 4.4, 8.6 Hz, 1H), 7.21 MS m / z 432.2, 434.2 [M+H] +

[0222] H) 1-[(2S)-2-{2-fluoro-5-[2-methyl-3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propyl]-1H-tetrazole The reaction and purification were carried out according to Example 1, Step H to give the title compound. 1 H NMR (300 MHz, DMSO-d6) δ 9.43 (s, 1H), 9.14 (d, J = 7.3 Hz, 1H), 8.01-8.10 (m, 1H), 7.97 (ddd, J = 1.9, 4.4, 8.5 Hz, 1H), 7.71 (d, J = 7.4 Hz, 1H), 7.53-7.64 (m, 2H), 7.42 (dd, J = 8.7, 10.9 Hz, 1H), 7.22 (dd, J = 3.6, 5.1 Hz, 1H), 5.07-5.18 (m, 1H), 4.89-4.98 (m, 1H), 4.79-4.89 (m, 1H), 2.66 (s, 3H), 1.41 (d, J = 6.2 Hz, 3H); MS m / z 436.4 [M+H] +

[0223] Example 61 1-[(2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propyl]-1H-1,2,4-triazole

[0224] A) ((2S)-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propan-1-ol To a mixture of (2S)-2-(3-bromophenoxy)propan-1-ol (35.0 g), (Bpin) (45.9 g), and KOAc (44.3 g) in toluene (100 mL) was added Pd(dppf)Cl (5.53 g). After stirring at 100 °C for 3 h under an argon atmosphere, the mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / hexane) to give the title compound (36.0 g). MS m / z 279.1 [M+H] +

[0225] B) (2S)-2-(3-{pyrazolo[1,5-a]pyrimidin-5-yl}phenoxy)propan-1-ol The reaction and purification were carried out according to Example 1, Step F to give the title compound. MS m / z 270.4 [M+H] +

[0226] C) (2S)-2-(3-{3-bromopyrazolo[1,5-a]pyrimidin-5-yl}phenoxy)propan-1-ol The reaction and purification were carried out according to Example 1, Step G to give the title compound. MS m / z 348.2 [M+H] +

[0227] D) (2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propan-1-ol The reaction and purification were carried out according to Example 1, Step H to give the title compound. MS m / z 352.1 [M+H] +

[0228] E) (2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propyl methanesulfonate To a mixture of (2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propan-1-ol (1.80 g) and TEA (777 mg) in THF (10 mL) was added MsCl (644 mg). The mixture was stirred at room temperature for 30 minutes. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure to give the crude title compound (2.20 g). The crude product was used in the next step without further purification. MS m / z 430.1 [M+H] +

[0229] F) 1-[(2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propyl]-1H-1,2,4-triazole To a mixture of (2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidin-5-yl]phenoxy}propyl methanesulfonate (100 mg) and K2CO3 (64.3 mg) in DMF (5.0 mL) was added 1,2,4-triazole (32.1 mg). The mixture was stirred at 100 °C for 15 hours. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH, EtOAc / hexane) to give the title compound (75.0 mg) as a yellow solid. 1 H NMR (300 MHz, DMSO-d6) δ 9.20 (d, J = 7.4 Hz, 1H), 8.67 (s, 1H), 8.58 (s, 1H), 7.97 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.83 (s, 1H), 7.73 (d, J = 7.4 Hz, 1H), 7.66 (dd, J = 5.1, 3.6 Hz, 1H), 7.45-7.30 (m, 2H), 7.17 (dd, J = 3.6, 1.1 Hz, 1H), 7.08 (dd, J = 8.1, 2.2 Hz, 1H), 4.95-5.05 (m, 1H), 4.59 (d, J = 5.6 Hz, 2H), 1.36 (d, J = 6.2 Hz, 3H); MS m / z 403.1 [M+H] +

[0230] Example 121 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile

[0231] A) 1-[(2S)-2-(2-fluoro-5-{imidazo[1,2-b]pyridazin-6-yl}phenoxy)propyl]-1H-tetrazole To a solution of 1-[(2S)-2-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propyl]-1H-tetrazole (33.0 g) and 6-chloroimidazo[1,2-b]pyridazine (14.6 g) in THF (320 mL) and water (80 mL) was added CsCO (61.8 g) and Pd(dppf)Cl-CHCl (7.74 g). The mixture was stirred at 70 °C under a nitrogen atmosphere for 1 hour. The mixture was diluted with water (300 mL) and extracted with EtOAc (400 mL × 3). The combined organic layers were washed with brine (500 mL), dried over NaSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (MeOH / Et0Ac) to give the title compound (13.0 g). 1 H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.99-8.01 (m, 2H), 7.79 (s, 1H), 7.55-7.57 (m, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.16-7.20 (m, 1H), 5.01-5.06 (m, 2H), 4.83-4.85 (m, 1H), 1.51 (d, J = 6.0 Hz, 3H)

[0232] B) 1-[(2S)-2-(5-{3-bromoimidazo[1,2-b]pyridazin-6-yl}-2-fluorophenoxy)propyl]-1H-tetrazole To a mixture of 1-[(2S)-2-(2-fluoro-5-{imidazo[1,2-b]pyridazin-6-yl}phenoxy)propyl]-1H-tetrazole (20.0 g) in DMF (300 mL) was added NBS (10.5 g). The mixture was stirred at 25° C. under a nitrogen atmosphere for 12 hours. The mixture was diluted with water (200 mL) and extracted with EtOAc (300 mL×3). The combined organic layers were washed with brine (200 mL), dried over NaSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc) to give the title compound (15.1 g). 1 H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.99-8.01 (m, 1H), 7.80 (s, 1H),7.62-7.64 (m, 2H), 7.46 (d, J = 6.4 Hz, 1H), 7.21-7.23 (m, 1H), 5.04-5.07 (m, 2H), 4.84-4.86 (m, 1H), 1.52 (d, J = 6.0 Hz, 3H)

[0233] C) 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile Pd(PPh3)2Cl2 (4.33 mg) was added to a mixture of 1-[(2S)-2-(5-{3-bromoimidazo[1,2-b]pyridazin-6-yl}-2-fluorophenoxy)propyl]-1H-tetrazole (50.0 mg), (2-cyanophenyl)boronic acid (19.3 mg), and Cs2CO3 (77.8 mg) in THF (5.0 mL) and water (1.0 mL). The mixture was stirred at 70 °C under a nitrogen atmosphere for 1 hour. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was crystallized from EtOAc to give the title compound (28.0 mg) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.39 (d, J = 5.8 Hz, 1H), 8.23 ​​(s, 1H), 8.07-8.13 (m, 2H), 7.97 (d, J = 5.8 Hz, 1H), 7.90-7.97 (m,1H), 7.81 (dd, J = 5.8, 3.0 Hz, 1H), 7.68-7.72 (m, 2H), 7.35-7.38 (m, 1H), 5.01-5.09 (m, 1H), 4.78-4.94 (m, 2H), 1.36 (d, J = 6.0 Hz, 3H); MS m / z 441.2 [M+H] +

[0234] Example 150 2-[5-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile

[0235] A) 5-chloro-3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridine and 5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazo[4,5-b]pyridine To a mixture of 5-chloro-3H-imidazo[4,5-b]pyridine (3.90 g) and DIPEA (6.53 g) in DMF (40 mL) was added SEMCl (3.6 mL). After stirring at 80° C. for 14 hours under a nitrogen atmosphere, additional SEMCl (1.3 mL) was added to the mixture. After stirring at 80° C. for 4 hours under a nitrogen atmosphere, the mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH, EtOAc / hexane) to give a mixture of the title compounds (4.93 g). MS m / z 284.2 [M+H] +

[0236] B) 1-[(2S)-2-[2-fluoro-5-(3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin-5-yl)phenoxy]propyl]-1H-tetrazole and 1-[(2S)-2-[2-fluoro-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazo[4,5-b]pyridin-5-yl)phenoxy]propyl]-1H-tetrazole The reaction and purification was carried out according to Example 284, Step D to give the title compound. MS m / z 470.3 [M+H] +

[0237] C) 1-[(2S)-2-(2-fluoro-5-{3H-imidazo[4,5-b]pyridin-5-yl}phenoxy)propyl]-1H-tetrazole To a mixture of 1-[(2S)-2-[2-fluoro-5-(3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin-5-yl)phenoxy]propyl]-1H-tetrazole and 1-[(2S)-2-[2-fluoro-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazo[4,5-b]pyridin-5-yl)phenoxy]propyl]-1H-tetrazole (7.48 g) in THF (40 mL) was added 1 M TBAF THF solution (14 mL). The mixture was stirred at 80° C. under a nitrogen atmosphere for 4 hours. The mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure to give the crude title compound (2.60 g). The crude product was used in the next step without further purification. 1H NMR (300 MHz, DMSO-d6) δ 12.62-13.31 (m, 1H), 9.42 (s, 1H), 8.39-8.51 (m, 1H), 7.98-8.18 (m, 1H), 7.68-7.86 (m, 3H), 7.25-7.36 (m, 1H), 5.01-5.12 (m, 1H), 4.75-4.93 (m, 2H), 1.36 (d, J = 6.1 Hz, 3H); MS m / z 340.3 [M+H] +

[0238] D) 2-[5-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile A mixture of 1-[(2S)-2-(2-fluoro-5-{3H-imidazo[4,5-b]pyridin-5-yl}phenoxy)propyl]-1H-tetrazole (250 mg), 2-chloropyridine-3-carbonitrile (152 mg), KPO (233 mg), tBuXPhos (62.5 mg), and Pd(dba) (67.4 mg) in DMA (15 mL) was stirred at 100 °C for 1 h under microwave irradiation. The mixture was quenched with water at room temperature and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / hexane) and silica gel column chromatography (NH, EtOAc / hexane) to give the title compound (8.00 mg) as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.91 (s, 1H), 8.83 (dd, J = 1.8, 4.9 Hz, 1H), 8.65 (s, 1H), 8.48 (dd, J = 1.8, 7.8 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.97 (dd, J = 2.1, 8.2 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.61 (dd, J = 4.9, 7.9 Hz, 1H), 7.53-7.58 (m, 1H), 7.18 (dd, J = 8.5, 11 Hz, 1H), 4.92 (dt, J = 2.9, MS m / z 442.3 [M+H] +

[0239] Example 173 4-[5-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridin-3-yl]-1-methyl-1H-imidazole-5-carbonitrile

[0240] A) 4-[(6-chloro-3-nitropyridin-2-yl)amino]-1-methyl-1H-imidazole-5-carbonitrile The reaction and purification was carried out according to Example 284, Step A to give the title compound. 1 H NMR (300 MHz, DMSO-d6) δ 10.15 (s, 1H), 8.57 (d, J = 8.5 Hz, 1H), 7.72 (s, 1H), 7.13 (d, J = 8.5 Hz, 1H), 3.59 (s, 3H); MS m / z 279.0 [M+H] +

[0241] B) 4-{5-chloro-3H-imidazo[4,5-b]pyridin-3-yl}-1-methyl-1H-imidazole-5-carbonitrile The reaction and purification was carried out according to Example 284, steps B and C, to give the title compound. MS m / z 259.1 [M+H] +

[0242] C) 4-[5-(4-fluoro-3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridin-3-yl]-1-methyl-1H-imidazole-5-carbonitrile The reaction and purification was carried out according to Example 284, Step D to give the title compound. 1 H NMR (300 MHz, DMSO-d6) δ 9.41 (s, 1H), 8.83 (s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.24 (s, 1H), 8.08 (dd, J = 2.0, 8.3 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.84 (ddd, J = 2.0, 4.4, 8.6 Hz, 1H), 7.32 (dd, J = 8.6, 11 Hz, 1H), 5.08-5.19 (m, 1H), 4.88-4.96 (m, 1H), 4.76-4.87 (m, 1H), 3.97 (s, 3H), 1.37 (d, J = 6.1 Hz, 3H); MS m / z 445.2 [M+H] +

[0243] Example 239 2-[6-(3-{[(2S)-1-(1H-tetrazol-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazin-3-yl]benzonitrile

[0244] A) Methyl (2S)-2-(3-bromophenoxy)propanoate To a mixture of 3-bromophenol (75.0 g), methyl (2R)-2-hydroxypropanoate (90.3 g), and PPh3 (171 g) in THF (1000 mL) was added DIAD (131 g) at 0 °C. The mixture was stirred at 20 °C under a nitrogen atmosphere for 12 hours. The mixture was diluted with water (1000 mL) and extracted with EtOAc (500 mL × 3). The combined organic layers were washed with brine (1000 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was triturated with a 15% solution of EtOAc in PE (500 mL) and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (41.0 g). 1 H NMR (400 MHz, CDCl3) δ 7.09-7.19 (m, 2H), 7.04 (d, J = 2.0 Hz, 1H), 6.75-6.81 (m, 1H), 4.74 (q, J = 6.8 Hz, 1H), 3.77 (s, 3H), 1.61 (d, J = 6.8Hz, 3H)

[0245] B) (2S)-2-(3-bromophenoxy)propan-1-ol To a mixture of methyl (2S)-2-(3-bromophenoxy)propanoate (41.0 g) in THF (200 mL) and MeOH (400 mL) was added NaBH (8.98 g) portionwise at 0 °C. The mixture was stirred at 20 °C for 12 hours under a nitrogen atmosphere. Saturated aqueous NH Cl (500 mL) and water (500 mL) were added to the mixture at 0 °C. The organic solvent was removed under reduced pressure. The residue was extracted with EtOAc (400 mL × 3). The combined organic layer was washed with brine (800 mL), dried over Na SO and concentrated under reduced pressure to give the title compound (35.0 g). 1 H NMR (400 MHz, CDCl3) δ 7.01-7.16 (m, 3H), 6.80-6.90 (m, 1H), 4.41-4.52 (m, 1H), 3.64-3.75 (m, 2H), 2.06 (brs, 1H), 1.26 (d, J = 6.0 Hz, 3H)

[0246] C) (2S)-2-(3-bromophenoxy)propyl methanesulfonate To a mixture of (2S)-2-(3-bromophenoxy)propan-1-ol (64.0 g) and TEA (56.1 g) in THF (700 mL) was added MsCl (44.4 g) dropwise at 0° C. for 0.5 hours. The mixture was stirred at 20° C. under a nitrogen atmosphere for 1 hour. The mixture was diluted with water (1000 mL) and extracted with EtOAc (500 mL×3). The combined organic layer was washed with brine (1000 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the title compound (82.0 g). 1 H NMR (400 MHz, CDCl3) δ 7.06-7.19 (m, 3H), 6.81-6.92 (m, 1H), 4.59-4.70 (m, 1H), 4.25-4.36 (m, 2H), 3.03 (s, 3H), 1.36 (d, J = 6.0 Hz, 3H)

[0247] D) 1-[(2S)-2-(3-bromophenoxy)propyl]-1H-tetrazole To a mixture of (2S)-2-(3-bromophenoxy)propyl methanesulfonate (82.0 g) in DMF (800 mL) was added K2CO3 (73.3 g) and 1H-tetrazole (37.2 g). The mixture was stirred at 80 °C under a nitrogen atmosphere for 12 hours. The mixture was concentrated under reduced pressure. The residue was poured into water (1500 mL) and extracted with EtOAc (800 mL × 3). The combined organic layer was washed with brine (1000 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (72.0 g). 1 H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 7.09-7.18 (m, 2H), 6.95-7.03 (m, 1H), 6.67-6.73 (m, 1H), 4.66-4.79 (m, 2H), 4.53-4.65 (m, 1H), 1.36 (d, J = 6.0 Hz, 3H)

[0248] E) 1-[(2S)-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propyl]-1H-tetrazole To a mixture of 1-[(2S)-2-(3-bromophenoxy)propyl]-1H-tetrazole (36.0 g), (Bpin) (48.4 g), and KOAc (25.0 g) in DMSO (500 mL) was added Pd(dppf)Cl-CHCl (10.4 g). The mixture was stirred at 100 °C for 2 hours. The mixture was diluted with water (2000 mL) and extracted with EtOAc (1000 mL × 3). The combined organic layers were washed with water (1000 mL × 2), dried over NaSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (63.0 g). 1 H NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 7.43 (d, J = 7.2 Hz, 1H), 7.25-7.34 (m, 2H), 6.90-6.97 (m, 1H), 4.74-4.86 (m, 2H), 4.56-4.65 (m, 1H), 1.30-1.42 (m, 15H); MS m / z 331.0 [M+H] +

[0249] F) 1-[(2S)-2-(3-{imidazo[1,2-b]pyridazin-6-yl}phenoxy)propyl]-1H-tetrazole To a solution of 1-[(2S)-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propyl]-1H-tetrazole (11.0 g), CsCO (21.7 g), and 6-chloroimidazo[1,2-b]pyridazine (5.12 g) in THF (100 mL) and water (25 mL) was added Pd(dppf)Cl-CHCl (2.72 g). The mixture was stirred at 70 °C under a nitrogen atmosphere for 1 hour. The mixture was diluted with water (100 mL) and extracted with EtOAc (150 mL × 3). The combined organic layers were washed with brine (100 mL), dried over NaSO, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc / PE) to give the title compound (8.00 g). 1 H NMR (400 MHz, CDCl3) δ 8.78 (s, 1H), 7.99-8.05 (m, 2H), 7.83 (s, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.39-7.46 (m, 3H), 6.93 (dd, J = 8.4, 2.8 Hz, 1H), 4.87-4.93 (m, 1H), 4.79-4.83 (m, 1H), 4.62-4.67 (m, 1H), 1.43 (d, J = 6.0 Hz, 3H)

[0250] G) 1-[(2S)-2-(3-{3-bromoimidazo[1,2-b]pyridazin-6-yl}phenoxy)propyl]-1H-tetrazole To a solution of 1-[(2S)-2-(3-{imidazo[1,2-b]pyridazin-6-yl}phenoxy)propyl]-1H-tetrazole (8.00 g) in DMF (70 mL) was added NBS (4.43 g). The mixture was stirred at 25° C. under a nitrogen atmosphere for 12 hours. The mixture was diluted with water (60 mL) and extracted with EtOAc (100 mL×3). The combined organic layers were washed with brine (100 mL), dried over NaSO, and concentrate...

Claims

1. Formula (II): 【Chemistry 1】 [During the ceremony, X １ is N or CR Ｘ１ where R Ｘ１ is a hydrogen atom, a halogen atom or C １－６ is an alkyl group; X ２ , X ３ and X ４ are each independently C or N, and X ２ , X ３ and X ４ one of which is N and the other two are C; Ring A ２ is an optionally further substituted benzene ring, an optionally further substituted 5- or 6-membered aromatic heterocycle, or an optionally further substituted 5- or 6-membered non-aromatic heterocycle, each of which is optionally fused to an optionally substituted 5- or 6-membered ring; Y １ is N or CR Ｙ１ where R Ｙ１ is a hydrogen atom; Y ２ is N or CR Ｙ２ where R Ｙ２ is a hydrogen atom, a halogen atom or a cyano group; Y ３ is N or CR Ｙ３ where R Ｙ３ is a hydrogen atom or a halogen atom; Y ４ is N or CR Ｙ４ where R Ｙ４ is a hydrogen atom or a halogen atom; Ring B ２ is a tetrazole or triazole, each of which is attached through a nitrogen atom; and R １ is C １－６ is an alkyl group. or a pharmaceutically acceptable salt thereof.

2. X １ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein is CH.

3. R １ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein is methyl.

4. Ring A ２ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: is a benzene ring, a 6-membered aromatic heterocycle, or a 6-membered non-aromatic heterocycle, each of which is further substituted with one cyano group and optionally further substituted.

5. Ring A 2 is (1) Depending on the circumstances (a) a cyano group, (b) a halogen atom, (c) In some cases (i) a halogen atom and (ii) a C 1-6 alkoxy group, a C 1-6 alkyl group substituted with 1 to 3 substituents selected from (d) a C 1-6 alkoxy group optionally substituted with 1 to 3 halogen atoms; a benzene ring further substituted with 1 to 5 substituents selected from (2) Depending on the circumstances (a) a cyano group, (b) a C 1-6 alkyl group optionally substituted with 1 to 3 halogen atoms; and (c) a C 1-6 alkoxy group or a 5- or 6-membered aromatic heterocycle further substituted with 1 to 4 substituents selected from (3) Depending on the circumstances (a) an oxo group, (b) a cyano group, and (c) a C 1-6 alkyl group, a 5- or 6-membered non-aromatic heterocycle further substituted with 1 to 4 substituents selected from 2. The compound of claim 1, wherein:

6. Ring A 2 is (1) Depending on the circumstances (a) a cyano group, (b) a halogen atom, (c) In some cases (i) a halogen atom and (ii) a C 1-6 alkoxy group a C 1-6 alkyl group substituted by 1 to 3 substituents selected from: (d) a C 1-6 alkoxy group optionally substituted with 1 to 3 halogen atoms; a benzene ring further substituted with 1 to 5 substituents selected from (2) Depending on the circumstances (a) a cyano group, (b) a C 1-6 alkyl group optionally substituted with 1 to 3 halogen atoms; and (c) a C 1-6 alkoxy group a pyridine ring further substituted with 1 to 4 substituents selected from (3) Depending on the circumstances (a) a cyano group and (b) a C 1-6 alkoxy group or a pyrimidine ring further substituted with 1 to 3 substituents selected from (4) Depending on the circumstances (a) a cyano group, (b) an oxo group, and (c) C 1-6 alkyl group a dihydropyridine ring further selected from 1 to 4 substituents selected from 2. The compound of claim 1, wherein:

7. Y １ , Y ２ , Y ３ and Y ４ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein at least one of: is N.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Y 1 is CH.

9. Formula (II-1): 【Chemistry 2】 wherein each symbol is as defined in claim 1.

2. The compound of claim 1, represented by: or a pharmaceutically acceptable salt thereof.

10. Ring A 2 is (1) Depending on the circumstances (a) a cyano group, (b) a halogen atom, (c) In some cases (i) a halogen atom and (ii) a C 1-6 alkoxy group a C 1-6 alkyl group further substituted with 1 to 3 substituents selected from (d) a C 1-6 alkoxy group optionally substituted with 1 to 3 halogen atoms; a benzene ring further substituted with 1 to 5 substituents selected from (2) Depending on the circumstances (a) a cyano group, (b) a C 1-6 alkyl group optionally substituted with 1 to 3 halogen atoms; and (c) a C 1-6 alkoxy group or a 5- or 6-membered aromatic heterocycle further substituted with 1 to 4 substituents selected from (3) Depending on the circumstances (a) an oxo group, (b) a cyano group, and (c) C 1-6 alkyl group a 5- or 6-membered non-aromatic heterocycle further substituted with 1 to 4 substituents selected from 10. The compound of claim 9, wherein:

11. Ring A 2 is (1) Depending on the circumstances (a) a cyano group, (b) a halogen atom, (c) In some cases (i) a halogen atom and (ii) a C 1-6 alkoxy group a C 1-6 alkyl group further substituted with 1 to 3 substituents selected from (d) a C 1-6 alkoxy group optionally substituted with 1 to 3 halogen atoms; a benzene ring further substituted with 1 to 5 substituents selected from (2) Depending on the circumstances (a) a cyano group, (b) a C 1-6 alkyl group optionally substituted with 1 to 3 halogen atoms; and (c) a C 1-6 alkoxy group a pyridine ring further substituted with 1 to 4 substituents selected from (3) Depending on the circumstances (a) a cyano group and (b) a C 1-6 alkoxy group or a pyrimidine ring further substituted with 1 to 3 substituents selected from (4) Depending on the circumstances (a) a cyano group, (b) an oxo group, and (c) C 1-6 alkyl group a dihydropyridine ring further substituted with 1 to 4 substituents selected from 10. The compound of claim 9, wherein:

12. Formula (III): 【Transformation 3】 [During the ceremony, X ２ , X ３ and X ４ are each independently C or N, and X ２ , X ３ and X ４ one of which is N and the other two are C; Ring A ３ is an optionally further substituted benzene ring, an optionally further substituted 6-membered nitrogen-containing aromatic heterocycle, or an optionally further substituted 6-membered nitrogen-containing non-aromatic heterocycle; Y １ is N or CR Ｙ１ where R Ｙ１ is a hydrogen atom; Y ２ is N or CR Ｙ２ where R Ｙ２ is a hydrogen atom, a halogen atom or a cyano group; Y ３ is N or CR Ｙ３ where R Ｙ３ is a hydrogen atom or a halogen atom; Y ４ is N or CR Ｙ４ where R Ｙ４ is a hydrogen atom or a halogen atom; and W is N or CH. or a pharmaceutically acceptable salt thereof.

13. formula; 【Chemistry 4】 The partial structure represented by the formula (A ３ -1) to (A ３ -9); 【Transformation 5】 [During the ceremony, Q １ is N or CR Ｑ１ where R Ｑ１ teeth (a) a hydrogen atom, (b) a cyano group, (c) a halogen atom, (d) a hydroxy group, (e) a carboxy group, (f) an amino group; (g) Optionally substituted C １－６ alkyl groups, (h) optionally substituted C １－６ alkoxy groups, (i) C １－６ alkyl-carbonyl groups, (j) C １－６ alkoxy-carbonyl groups, (k) optionally substituted mono- or di-C １－６ alkylamino groups, (l) Optionally substituted mono- or di-C １－６ alkyl-carbonylamino groups, (m) Mono- or di-C １－６ alkoxy-carbonylamino groups, (n) mono- or di-C １－６ alkyl-carbamoyl groups, (o) The C １－６ alkylsulfinylideneamino group, (p) C ３－１０ cycloalkyl groups, (q) Optionally substituted C ３－１０ cycloalkyloxy groups, (r) a 3- to 8-membered monocyclic non-aromatic heterocyclic group, (s) optionally substituted 3- to 8-membered monocyclic non-aromatic heterocyclyloxy; (t) an optionally substituted 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group, or (u) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group, Q ２ is N or CR Ｑ２ where R Ｑ２ teeth (a) a hydrogen atom, (b) a halogen atom or (c) C １－６ alkoxy groups, Q ３ is N or CR Ｑ３ , where R Ｑ３ teeth (a) a hydrogen atom, (b) a cyano group, (c) a halogen atom, (d) a carboxy group; (e) optionally substituted C １－６ alkyl groups, (f) optionally substituted C １－６ alkoxy groups, (g) C １－６ alkyl-carbonyl groups, (h) C １－６ alkoxy-carbonyl groups, (i) Mono- or di-C １－６ alkylamino groups, (j) optionally substituted mono- or di-C １－６ alkyl-carbamoyl groups, (k) J-C １－６ Alkyl sulfinylidene amino group or (l) 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group and Q ４ is N or CR Ｑ４ , where R Ｑ４ teeth (a) a hydrogen atom or (b) Halogen atoms and Q １ , Q ２ , Q ３ and Q ４ wherein each N is optionally oxidized; R Ｎ１ is a hydrogen atom or C １－６ is an alkyl group; R Ｎ２ is a hydrogen atom or C １－６ is an alkyl group; R Ｎ３ is a hydrogen atom or C １－６ is an alkyl group; and R Ｎ４ is a hydrogen atom or C optionally substituted with 1 to 3 halogen atoms １－６ is an alkyl group.

13. The compound of claim 12, represented by: or a pharmaceutically acceptable salt thereof.

14. Y １ , Y ２ , Y ３ and Y ４ 13. The compound of claim 12, or a pharmaceutically acceptable salt thereof, wherein at least one of is N.

15. Formula (III-1): 【Transformation 6】 wherein each symbol is as defined in claim 12.

13. The compound of claim 12, represented by: or a pharmaceutically acceptable salt thereof. 【Request Item 16】 【Chemistry 7】 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

17. Structure 【Transformation 8】 or a pharmaceutically acceptable salt thereof.

18. Structure 【Chemistry 9】 A compound having the formula:

19. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 18.

20. 20. The pharmaceutical of claim 19, which is a calcium / calmodulin-dependent protein kinase II inhibitor.

21. 20. The pharmaceutical of claim 19, which is a drug for preventing or treating heart disease.

22. 22. The pharmaceutical of claim 21, wherein the cardiac disease is selected from catecholaminergic polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmia.

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