Use of condensed heteroaryl compounds and their role as CaMKII inhibitors

Abstract

This invention provides a condensed heteroaryl compound having CaMKII inhibitory activity, which is 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, and fatal arrhythmias). [Solution] Formula (I): JPEG2026086814000103.jpg5175 A compound represented by or a pharmaceutically acceptable salt thereof is provided.

Description

[Technical Field]

[0001] Technical field The present invention relates to a condensed heteroaryl compound having calcium / calmodulin-dependent protein kinase II (sometimes abbreviated as "CaMKII" herein) inhibitory activity, which is expected to be useful as an agent for the prevention or treatment of heart diseases (particularly catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmias). [Background technology]

[0002] Cardiac disease, including heart failure, arrhythmias, myocardial infarction, angina pectoris, and valvular heart disease, is a disease with a high mortality rate. In drug treatment of cardiac disease, symptoms improve through control of risk factors and symptomatic treatment. However, patient satisfaction with treatment remains low, and there is currently no curative treatment.

[0003] The calcium-calmodulin complex is a serine / threonine protein kinase containing Ca 2+ It binds to and activates calmodulin-dependent protein kinase (CaMK). 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 to the calcium-calmodulin complex, CaMKII is activated by amino acid modification due to oxidative stress or hyperglycemia. Upon kinase activation, CaMKII binds to its substrate, the transcription factor Ca 2+ Cellular functions are regulated by phosphorylation of proteins that have functions in organelle uptake / excretion, proteins that control muscle contraction and relaxation, and channels that control intracellular ion concentration.

[0004] Several studies 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 Literature 1-4). Cardiac hypertrophy and heart failure have been reported in transgenic mice that overexpress CaMKII δ in the heart (Non-Patent Literature 4). Protective effects against heart failure, cardiac hypertrophy, myocardial infarction, and arrhythmias have been reported in mice through pharmacological inhibitory studies and genetic gene deletion studies (Non-Patent Literature 5-7). For catecholamine-induced polymorphic ventricular tachycardia, mutant ryanodine knock-in mice (RyR2 R4496C+ / - The improvement of disease status by CaMKII inhibitors in mice has been reported (Non-Patent Literature 8). These findings suggest the efficacy of CaMKII inhibitors in the prevention and / or treatment of cardiovascular diseases, including heart failure, cardiac hypertrophy, myocardial infarction, and arrhythmias.

[0005] Recently, CaMKII has been suggested to exacerbate the proliferation or metastasis of certain types of cancer (Non-Patent Literature 9). Furthermore, CaMKII inhibition has been suggested to have therapeutic effects on acute renal failure, intimal hyperplasia, hepatic fibrosis, stroke, pain, and rheumatoid arthritis (Non-Patent Literature 10-15).

[0006] However, genetic methods only achieve protein deletion or overexpression of inhibitory proteins, which is a different mechanism from the transient inhibition of kinase activity; therefore, the effects of kinase inhibitors cannot always be expected. Furthermore, the inhibitors already reported are either low kinase selectivity for CaMKII or unsuitable for oral or chronic administration, and are therefore unsuitable for use as pharmaceuticals for CaMKII selective inhibitors.

[0007] The following compounds are known as heterocyclic compounds. Patent Document 1 describes the following compound (I): [ka] [In the formula, each symbol is defined in Patent Document 1.] This document describes that the compound is an FLT3 inhibitor and is useful in treating conditions such as acute myeloid leukemia.

[0008] Patent Document 2 contains the following formula (I): [ka] [In the formula, each symbol is defined in Patent Document 2.] The compound is described as a Syk (spleen tyrosine kinase) inhibitor and is useful in treating diseases or conditions mediated by Syk (e.g., rheumatism).

[0009] Patent Document 3 contains the following formula (I): [ka] [In the formula, each symbol is defined in Patent Document 3.] The compound is described as an mGluR (metabolite glutamate receptor) 5 modulator and is useful in treating or preventing diseases or conditions involving mGluR5 (e.g., pain disorders, anxiety, depression, Alzheimer's disease, Parkinson's disease, etc.).

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

[0011] Patent Document 5 contains the following formula (I): [ka] [In the formula, each symbol is defined in Patent Document 5.] The compound is described as a kinase inhibitor (such as p38 kinase) and is useful in reducing ischemic cell death (especially traumatic neuronal cell death).

[0012] Patent Document 6 shows the following formula (I): [ka] [In the formula, each symbol is defined in Patent Document 6.] The compound is described as a calcium / calmodulin-dependent protein kinase II inhibitor and is useful for 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 a condensed heteroaryl compound having a CaMKII inhibitory action, which is 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).

Means for Solving the Problems

[0016] The present inventors conducted intensive research in an attempt to solve the above problems, and found that the compound of the following formula (I) has a CaMKII inhibitory action, and thus is 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), leading to the completion of the present invention.

[0017] Therefore, the present invention provides the following. [1] Formula (I):

Chemical formula

[0018] [2] The compounds or pharmaceutically acceptable salts of the above [1], wherein V is O. [3] Ring B 1 The compounds or pharmaceutically acceptable salts of [1] above, wherein the compound is a five-membered aromatic heterocycle which may be further substituted in some cases. [4] The compounds of [1] above or pharmaceutically acceptable salts wherein Z is optionally a substituted ethylene group. [5] X 5 A compound or pharmaceutically acceptable salt of the above [1], wherein N is present. [6] X 6 A compound or pharmaceutically acceptable salt of the above [1], wherein CH is CH. [7] Y 1 , Y 2 , Y 3 and Y 4 A compound or pharmaceutically acceptable salt of the above [1], wherein at least one of the elements is N.

[0019] [8] Equation (I-1): [ka] [In the formula, each symbol is defined as in [1] above.] A compound represented by [1] above, or a pharmaceutically acceptable salt thereof (sometimes referred to here as compound (I-1)).

[0020] [9] Formula (II): [ka] [During the ceremony, X 1 is N or CR X1 And here, R X1 is a hydrogen atom, halogen atom or C 1-6 It is an alkyl group; X 2 , X 3 and X 4 Each is independently either C or N, and X 2 , X 3 and X 4 One of them is N, and the other two are C; Ring A 2 These are, in some cases, further substituted benzene rings, in some cases further substituted five- or six-membered aromatic heterorings, or in some cases further substituted five- or six-membered non-aromatic heterorings, each of which is in some cases fused with a further substituted five- or six-membered ring; Y 1 is N or CR Y1 And here, R Y1 is a hydrogen atom; Y 2 is N or CR Y2 And here, R Y2 is a hydrogen atom, a halogen atom, or a cyano group; Y 3 is N or CR Y3 And here, R Y3 is a hydrogen atom or a halogen atom; Y 4 is N or CR Y4 And here, R Y4 is a hydrogen atom or a halogen atom; Ring B 2 It is a five-membered aromatic heteroring that may be further substituted in some cases; and R 1 is C 1-6 It is an alkyl group. The compound or a pharmaceutically acceptable salt thereof (sometimes referred to here as compound (II)).

[0021]

[10] X 1 A compound or pharmaceutically acceptable salt of the above [9], wherein is CH.

[11] Ring B 2 The compounds or pharmaceutically acceptable salts of the above [9], wherein each is a tetrazole or triazole, each bonded at its nitrogen.

[12] R 1 A compound or pharmaceutically acceptable salt of the above [9], wherein the compound is methyl.

[13] Ring A 2 The compounds of [9] above or pharmaceutically acceptable salts thereof, wherein is a benzene ring, a six-membered aromatic heterocycle, or a six-membered non-aromatic heterocycle, each of which is further substituted with one cyano group, and optionally further substituted.

[14] Y 1 , Y 2 , Y 3 and Y 4 A compound or pharmaceutically acceptable salt of the above [9], wherein at least one of the elements is N.

[0022]

[15] Formula (II-1): [ka] [Wherein each symbol is as defined in the above [9].] A compound represented by the above [9] compound or a pharmaceutically acceptable salt thereof (hereinafter sometimes referred to as compound (II-1)).

[0023]

[16] Formula (III):

Chemical formula

[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 And here, R Q1 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atom, (d) Hydroxyl group, (e) Carboxylic group, (f) amino group, (g) C which is substituted in some cases 1-6 alkyl group, (h) C which is replaced in some cases 1-6 Alkoxy group, (I C 1-6 Alkyl-carbonyl group, (j) C 1-6 Alkoxy-carbonyl group, (k) Mono- or di-C as may be substituted. 1-6 Alkylamino group, (l) Mono- or di-C as may be substituted. 1-6 Alkyl-carbonylamino group, (m) Mono- or di-C 1-6 Alkoxy-carbonylamino group, (n) mono- or di-C 1-6 Alkyl-carbamoyl group, (o) G-C 1-6 Alkyl sulfinylidene amino group, (p) C 3-10 Cycloalkyl groups, (q) C which is replaced in some cases 3-10 Cycloalkyloxy group, (r) 3-8 member monocyclic non-aromatic heterocyclic group, (s) A 3- to 8-membered monocyclic non-aromatic heterocyclyloxy that may be substituted in some cases. (t) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group which may be substituted in some cases. (u) 3-8 membered monocyclic non-aromatic heterocyclidene amino group And, Q 2 is N or CR Q2 And here, R Q2 teeth (a) Hydrogen atom, (b) Halogen atom or (c) C 1-6 Alkoxy group And, Q 3 is N or CR Q3 And here, R Q3 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atom, (d) Carboxylic group, (e) C which is replaced in some cases 1-6 alkyl group, (f) C which is replaced in some cases 1-6 Alkoxy group, (g) C 1-6 Alkyl-carbonyl group, (h) C 1-6 Alkoxy-carbonyl group, (i) Mono- or di-C 1-6 Alkylamino group, (j) Mono- or di-C as may be substituted. 1-6 Alkyl-carbamoyl group, (k) G-C 1-6 Alkyl sulfinylidene amino group or (l) 3-8 membered monocyclic non-aromatic heterocyclidene amino group And, Q 4 is N or CR Q4 And here, R Q4 teeth (a) A hydrogen atom or (b) Halogen atom And Q 1 Q 2 Q 3 and Q 4 The N atoms are oxidized in each case; R N1 is a hydrogen atom or C 1-6 It is an alkyl group; R N2 is a hydrogen atom or C 1-6 It is an alkyl group; R N3 is a hydrogen atom or C 1-6 It is an alkyl group; and R N4 C is substituted with hydrogen atoms or, in some cases, 1 to 3 halogen atoms. 1-6 It is an alkyl group. A substructure represented by the above

[16] compound or a pharmaceutically acceptable salt thereof.

[18] Y 1 , Y 2 , Y 3 and Y 4 At least one of the compounds

[16] above is N, or a pharmaceutically acceptable salt thereof.

[0025]

[19] Formula (III-1): [ka] [In the formula, each symbol is defined as in

[16] above.] A compound represented by the above

[16] , or a pharmaceutically acceptable salt thereof (sometimes referred to here as compound (III-1)).

[0026]

[20] 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]pyridine-3-carbonitrile, 2-[6-(3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]pyridine-3-carbonitrile, 2-[5-(3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridine-3-yl]pyridine-3-carbonitrile, 4-Fluoro-2-[6-(5-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-3-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, 4-Methoxy-2-[6-(3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]pyridine-3-carbonitrile, 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]-4-methoxypyridine-3-carbonitrile, 4-Fluoro-2-[5-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)-3H-imidazo[4,5-b]pyridine-3-yl]benzonitrile, 4-Fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyrazine-2-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, 4-Fluoro-2-methoxy-6-[5-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)-3H-imidazo[4,5-b]pyridine-3-yl]benzonitrile and 4-Fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, A compound or pharmaceutically acceptable salt selected from the group consisting of the following.

[0027]

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

[22] The drugs described in

[21] above, which are calcium / calmodulin-dependent protein kinase II inhibitors.

[23] The medicines described in

[21] above, which are for the prevention or treatment of heart disease.

[24] The medicines described in

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

[0028]

[25] The compounds or pharmaceutically acceptable salts of the above [1] for use in the prevention or treatment of heart disease.

[26] The compound or pharmaceutically acceptable salt of the above

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

[0029]

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

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

[29] The method described in

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

[0030]

[30] Use of the compounds or pharmaceutically acceptable salts of the above [1] for the manufacture of agents for the prevention or treatment of heart disease.

[31] Use of the above

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

[0031] The present invention may provide a condensed heteroaryl compound having excellent CaMKII inhibitory activity, which is 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, and fatal arrhythmias). [Modes for carrying out the invention]

[0032] (Detailed description of the invention) The present invention will be described in detail below.

[0033] The definitions of each substituent used herein are described in detail below. Unless otherwise specified, each substituent has the following definitions: In this specification, examples of "halogen atoms" include fluorine, chlorine, bromine, and iodine, which, in addition to carbon atoms, contain 1 to 4 heteroatoms selected from nitrogen, sulfur, and oxygen atoms as ring constituent atoms. In this specification, "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. In this specification, "C which may be halogenated" 1-6 Examples of alkyl groups include C, which may have 1 to 7, preferably 1 to 5, halogen atoms. 1-6It contains alkyl groups. Specific examples 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. In this specification, "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. In this specification, "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. In this specification, "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. In this specification, "C which may be halogenated" 3-10 An example of a "cycloalkyl group" is a C group having 1 to 7, preferably 1 to 5, halogen atoms. 3-10It contains cycloalkyl groups. Specific examples include cyclopropyl, 2,2-difluorocyclopropyl, 2,3-difluorocyclopropyl, cyclobutyl, difluorocyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In this specification, "C 3-10 Examples of "cycloalkenyl groups" include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. In this specification, "C 6-14 Examples of "aryl groups" include phenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, and 9-anthryl. In this specification, "C 7-16 Examples of "aralkyl groups" include benzyl, phenethyl, naphthylmethyl, and phenylpropyl.

[0034] In this specification, "C 1-6 Examples of "alkoxy groups" include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, and hexyloxy. In this specification, "C which may be halogenated" 1-6 An example of an "alkoxy group" is a C group having 1 to 7, preferably 1 to 5, halogen atoms. 1-6 It contains alkoxy groups. Specific examples include methoxy, difluoromethoxy, trifluoromethoxy, ethoxy, 2,2,2-trifluoroethoxy, propoxy, isopropoxy, butoxy, 4,4,4-trifluorobutoxy, isobutoxy, sec-butoxy, pentyloxy, and hexyloxy. In this specification, "C 3-10 Examples of "cycloalkyloxy groups" include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, and cyclooctyloxy. In this specification, "C 1-6Examples of alkylthio groups include methylthio, ethylthio, propylthio, isopropylthio, butylthio, sec-butylthio, tert-butylthio, pentylthio, and hexylthio. In this specification, "C which may be halogenated" 1-6 An example of an alkylthio group is a C group having 1 to 7, preferably 1 to 5, halogen atoms. 1-6 It contains alkylthio groups. Specific examples include methylthio, difluoromethylthio, trifluoromethylthio, ethylthio, propylthio, isopropylthio, butylthio, 4,4,4-trifluorobutylthio, pentylthio, and hexylthio. In this specification, "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. In this specification, "C which may be halogenated" 1-6 An example of an alkyl-carbonyl group is a C group having 1 to 7, preferably 1 to 5, halogen atoms. 1-6 It contains alkyl-carbonyl groups. Specific examples include acetyl, chloroacetyl, trifluoroacetyl, trichloroacetyl, propanoyl, butanoyl, pentanoyl, and hexanoyl. In this specification, "C 1-6 Examples of "alkoxy-carbonyl groups" include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, and hexyloxycarbonyl. In this specification, "C 6-14 Examples of "aryl-carbonyl groups" include benzoyl, 1-naphthoyl, and 2-naphthoyl. In this specification, "C 7-16 Examples of "aralkyl-carbonyl groups" include phenylacetyl and phenylpropionyl. In this specification, examples of "5-14 member aromatic heterocyclylcarbonyl groups" include nicotinoyl, isonicotinoyl, tenoyl, and froyl. In this specification, examples of "3- to 14-membered non-aromatic heterocyclyl carbonyl groups" include morpholinyl carbonyl, piperidinyl carbonyl, and pyrrolidinyl carbonyl.

[0035] In this specification, "mono- or di-C" is used. 1-6 Examples of alkyl-carbamoyl groups include methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, and N-ethyl-N-methylcarbamoyl. In this specification, "mono- or di-C" is used. 7-16 Examples of the "aralkyl-carbamoyl group" include benzylcarbamoyl and phenethylcarbamoyl. In this specification, "C 1-6 Examples of alkylsulfonyl groups include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, sec-butylsulfonyl, and tert-butylsulfonyl. In this specification, "C which may be halogenated" 1-6 An example of an alkylsulfonyl group is a C group having 1 to 7, preferably 1 to 5, halogen atoms. 1-6 It contains alkylsulfonyl groups. Specific examples include methylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, 4,4,4-trifluorobutylsulfonyl, pentylsulfonyl, and hexylsulfonyl. In this specification, "C 6-14 Examples of "arylsulfonyl groups" include phenylsulfonyl, 1-naphthylsulfonyl, and 2-naphthylsulfonyl.

[0036] In this specification, examples of "substituents" include halogen atoms, cyano groups, nitro groups, optionally substituted hydrocarbon groups, optionally substituted heterocyclic groups, acyl groups, optionally substituted amino groups, optionally substituted carbamoyl groups, optionally substituted thiocarbamoyl groups, optionally substituted sulfamoyl groups, optionally substituted hydroxyl groups, optionally substituted sulfanyl (SH) groups, and optionally substituted silyl groups. In this specification, examples of "hydrocarbon group" (including "hydrocarbon group" in "optionally substituted hydrocarbon group") are C 1-6 Alkyl 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 group and C 7-16 Contains an aralkyl group.

[0037] In this specification, examples of "optionally substituted hydrocarbon groups" include hydrocarbon groups having substituents optionally selected from the following substituent group A. [Substituent Group A] (1) Halogen atom, (2) Nitro group, (3) Cyano group, (4) Oxo group, (5) Hydroxyl group, (6) C which may be halogenated in some cases 1-6 Alkoxy group, (7) C 6-14 Aryloxy groups (e.g., phenoxy, naphthoxy), (8) C 7-16 Aralkyloxy group (e.g., benzyloxy), (9) 5-14 member aromatic heterocyclyloxy group (e.g., pyridyloxy), (10) 3-14 member 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) 5-14 member aromatic heterocyclylcarbonyloxy group (e.g., nicotinoyloxy), (17) 3-14 member non-aromatic heterocyclylcarbonyloxy groups (e.g., morpholinylcarbonyloxy, piperidinylcarbonyloxy), (18) C which may be halogenated in some cases 1-6 Alkyl sulfonyloxy groups (e.g., methyl sulfonyloxy, trifluoromethyl sulfonyloxy), (19) C depending on the case 1-6 C substituted with an alkyl group 6-14 Aryl sulfonyloxy groups (e.g., phenylsulfonyloxy, toluenesulfonyloxy), (20) C which may be halogenated in some cases 1-6 Alkylthio group, (21) 5-14 member aromatic heterocyclic group, (22) 3-14 member non-aromatic heterocyclic groups, (23) Formyl group, (24) Carboxy group, (25) C which may be halogenated in some cases 1-6 Alkyl-carbonyl group, (26) C 6-14 Aryl-carbonyl group, (27) 5-14 member aromatic heterocyclylcarbonyl group, (28) 3-14 member non-aromatic heterocyclylcarbonyl group, (29) C 1-6 Alkoxy-carbonyl group, (30) C 6-14 Aryloxycarbonyl groups (e.g., phenyloxycarbonyl, 1-naphthyloxycarbonyl, 2-naphthyloxycarbonyl), (31) C 7-16 Aralkyloxycarbonyl group (e.g., benzyloxycarbonyl, phenethyloxycarbonyl), (32) Carbamoyl group, (33) Thiocarbamoyl group, (34) Mono- or di-C 1-6 Alkyl-carbamoyl group, (35) C 6-14 Aryl-carbamoyl group (e.g., phenylcarbamoyl), (36) 5-14 member aromatic heterocyclylcarbamoyl groups (e.g., pyridylcarbamoyl, thienylcarbamoyl), (37) 3-14 member non-aromatic heterocyclylcarbamoyl groups (e.g., morpholinylcarbamoyl, piperidinylcarbamoyl), (38) C which may be halogenated in some cases 1-6 Alkyl sulfonyl group, (39) C 6-14 Aryl sulfonyl group, (40) 5-14 member aromatic heterocyclylsulfonyl groups (e.g., pyridylsulfonyl, thienylsulfonyl), (41) C which may be halogenated in some cases 1-6 Alkyl sulfinyl group, (42) C 6-14 Aryl sulfinyl groups (e.g., phenyl sulfinyl, 1-naphthyl sulfinyl, 2-naphthyl sulfinyl), (43) 5-14 member 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 group (e.g., phenylamino), (47) 5-14 member aromatic heterocyclylamino group (e.g., pyridylamino), (48) C 7-16 Aralkylamino group (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 group (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 Aralkyloxycarbonylamino group (e.g., benzyloxycarbonylamino), (55) C 1-6 Alkylsulfonylamino group (e.g., methylsulfonylamino, ethylsulfonylamino), (56) C 6-14 Aryl sulfonyl amino group, depending on the case, C 1-6Substituting with alkyl groups (e.g., phenylsulfonylamino, toluenesulfonylamino), (57) C which may be halogenated in some cases 1-6 alkyl group, (58) C 2-6 Alkenyl group, (59) C 2-6 Alkynyl group, (60) C 3-10 Cycloalkyl groups, (61) C 3-10 Cycloalkenyl group and (62) C 6-14 Aryl group.

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

[0039] In this specification, examples of "aromatic heterocyclic groups" (including "5-14 member aromatic heterocyclic groups") include 5-14 member (preferably 5-10 member) aromatic heterocyclic groups. Examples of preferred "aromatic heterocyclic groups" are 5-membered or 6-membered monocyclic aromatic heterocyclic groups, such as thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridadinyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, triazolyl, tetrazolyl, triazinyl, etc.; and 8-14 membered condensed polycyclic (preferably bicyclic or tricyclic) aromatic heterocyclic groups, such as benzothiophenyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, imidazopyridinyl, thienopyridinyl, phlopyridinyl, pyrrolopyridinyl, pyrazolopyridinyl, oxazolopyridinyl, thiazolopyridinyl, imidazopyridinyl, imidazopyridinyl, thienopyridinyl, phlopyridinyl This includes pyrrolopyrimidinyl, pyrazolopyrimidinyl, oxazolopyrimidinyl, thiazolopyrimidinyl, pyrazolotriazinyl, naphtho[2,3-b]thienyl, phenoxathiinyl, indolyl, isoindolyl, 1H-indazolyl, prinyl, isoquinolyl, quinolyl, phthalazinyl, naphthilidinyl, quinoxalinyl, quinazolinyl, cinnolinyl, carbazolyl, β-carbolinyl, phenanthiazinyl, acridinyl, phenazinyl, phenothiazinyl, phenosadinyl, etc.

[0040] In this specification, examples of "non-aromatic heterocyclic groups" (including "3-14 member non-aromatic heterocyclic groups") include 3-14 member (preferably 4-10 member) non-aromatic heterocyclic groups that, in addition to carbon atoms, contain 1-4 heteroatoms selected from nitrogen, sulfur, and oxygen atoms as ring constituent atoms. Examples of preferred "non-aromatic heterocyclic groups" include 3- to 8-membered monocyclic non-aromatic heterocyclic groups, such as azilidinyl, oxyranil, thyranil, azetidinil, oxetanil, thietanil, tetrahydrothienyl, tetrahydrofuranil, pyrrolinil, pyrrolidinyl, imidazolinil, imidazolidinyl, oxazolinil, oxazolidinyl, pyrazolinil, pyrazolidinyl, thiazolinil, thiazolidinyl, and tetrahydroisothiazolyl tetrahydrooxazolyl, tetrahydroisoxazolyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydropyridinyl, dihydrothiopyranil, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranil, tetrahydropyranil, tetrahydrothiopyranil, morpholinyl, thiomorpholinyl, azepanil, diazepanil, azepinil, oxepanil, azokanil, diazokanil, etc.; and 9-14 membered condensed polycyclic (preferably bicyclic 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, tetrahydrobenzal This includes zepinyl, tetrahydroquinoxalinyl, tetrahydrophenantridinyl, hexahydrophenothiazinyl, hexahydrophenoxadinyl, tetrahydrophthalazinyl, tetrahydronaphthilidinyl, tetrahydroquinazolinyl, tetrahydrosinnolinyl, tetrahydrocarbazolyl, tetrahydro-β-carbolinyl, tetrahydroacrydinyl, tetrahydrophenadinyl, tetrahydrothioxanthenyl, octahydroisoquinolyl, and others.

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

[0042] In this specification, examples of "acyl group" are, in each case, "a halogen atom, and in each case, a halogenated C." 1-6 C having 1 to 3 substituents selected from alkoxy, hydroxyl, nitro, cyano, amino, and carbamoyl groups. 1-6 Alkyl 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 The compound includes a formyl group, carboxyl group, carbamoyl group, thiocarbamoyl group, sulfino group, sulfo group, sulfamoyl group, and phosphono group, having one or two substituents selected from an aralkyl group, a 5-14 membered aromatic heterocyclic group, and a 3-14 membered non-aromatic heterocyclic group. Examples of "acyl groups" also include hydrocarbon-sulfonyl groups, heterocyclylsulfonyl groups, hydrocarbon-sulfinyl groups, and heterocyclylsulfinyl groups. Here, hydrocarbon-sulfonyl group refers to a hydrocarbon-bonded sulfonyl group, heterocyclylsulfonyl group refers to a heterocyclic-bonded sulfonyl group, hydrocarbon-sulfinyl group refers to a hydrocarbon-bonded sulfinyl group, and heterocyclylsulfinyl group refers to a heterocyclic-bonded sulfinyl group. Examples of preferred "acyl groups" include formyl group, carboxyl group, and C 1-6 Alkyl-carbonyl group, C 2-6 Alkenyl-carbonyl group (e.g., crotonoyl), C 3-10Cycloalkyl-carbonyl group (e.g., cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, cycloheptanecarbonyl), C 3-10 Cycloalkenyl-carbonyl group (e.g., 2-cyclohexenecarbonyl), C 6-14 Aryl-carbonyl group, C 7-16 Aralkyl-carbonyl group, 5-14 member aromatic heterocyclylcarbonyl group, 3-14 member non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl group, C 6-14 Aryloxycarbonyl group (e.g., phenyloxycarbonyl, naphthyloxycarbonyl), C 7-16 Aralkyloxycarbonyl groups (e.g., benzyloxycarbonyl, phenethyloxycarbonyl), carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 2-6 Alkenyl-carbamoyl group (e.g., diallylcarbamoyl), mono- or di-C 3-10 Cycloalkyl-carbamoyl group (e.g., cyclopropylcarbamoyl), mono- or di-C 6-14 Aryl-carbamoyl group (e.g., phenylcarbamoyl), mono- or di-C 7-16 Aralkyl-carbamoyl group, 5-14 member 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 group (e.g., diallylthiocarbamoyl), mono- or di-C 3-10 Cycloalkyl-thiocarbamoyl groups (e.g., cyclopropylthiocarbamoyl, cyclohexylthiocarbamoyl), mono- or di-C 6-14 Aryl-thiocarbamoyl group (e.g., phenylthiocarbamoyl), mono- or di-C 7-16Aralkyl-thiocarbamoyl group (e.g., benzylthiocarbamoyl, phenethylthiocarbamoyl), 5-14 member aromatic heterocyclylthiocarbamoyl group (e.g., pyridylthiocarbamoyl), sulfino group, C 1-6 Alkyl sulfinyl group (e.g., methyl sulfinyl, ethyl sulfinyl), sulfo group, C 1-6 Alkyl sulfonyl group, C 6-14 Aryl sulfonyl groups, phosphono groups, and mono- or di-C groups 1-6 It contains alkylphosphono groups (e.g., dimethylphosphono, diethylphosphono, diisopropylphosphono, dibutylphosphono).

[0043] In this specification, an example of an optionally substituted amino group is an optionally substituted C group having 1 to 3 substituents each optionally selected from substituent group A. 1-6 Alkyl 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, 5-14 member aromatic heterocyclylcarbonyl group, 3-14 member non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl groups, 5-14 member aromatic heterocyclic groups, carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 7-16 Aralkyl-carbamoyl group, C 1-6 Alkyl sulfonyl group and C 6-14 It contains an amino group having one or two substituents selected from arylsulfonyl groups. Examples of amino groups that are preferably substituted include amino groups, mono- or di-(occasionally halogenated) C 1-6 Alkyl)amino group (e.g., methylamino, trifluoromethylamino, dimethylamino, ethylamino, diethylamino, propylamino, dibutylamino), mono- or di-C2-6 Alkenylamino group (e.g., diallylamino), mono- or di-C 3-10 Cycloalkylamino groups (e.g., cyclopropylamino, cyclohexylamino), mono- or di-C 6-14 Arylamino group (e.g., phenylamino), mono- or di-C 7-16 Aralkylamino groups (e.g., benzylamino, dibenzylamino), mono- or di-(sometimes halogenated C) 1-6 Alkyl)-carbonylamino group (e.g., acetylamino, propionylamino), mono- or di-C 6-14 Aryl-carbonylamino group (e.g., benzoylamino), mono- or di-C 7-16 Aalkyl-carbonylamino group (e.g., benzylcarbonylamino), mono- or di-5-14 member aromatic heterocyclylcarbonylamino group (e.g., nicotinoylamino, isonicotinoylamino), mono- or di-3-14 member non-aromatic heterocyclylcarbonylamino group (e.g., piperidinylcarbonylamino), mono- or di-C 1-6 Alkoxy-carbonylamino groups (e.g., tert-butoxycarbonylamino), 5-14 member aromatic heterocyclylamino groups (e.g., pyridylamino), carbamoylamino groups, (mono- or di-C) 1-6 Alkyl-carbamoyl)amino group (e.g., methylcarbamoylamino), (mono- or di-C) 7-16 Aalkyl-carbamoyl)amino group (e.g., benzylcarbamoylamino), C 1-6 Alkylsulfonylamino group (e.g., methylsulfonylamino, ethylsulfonylamino), C 6-14 Aryl sulfonylamino group (e.g., phenylsulfonylamino), (C 1-6 Alkyl)(C 1-6 Alkyl-carbonyl)amino group (e.g., N-acetyl-N-methylamino) and (C 1-6 Alkyl)(C 6-14 It contains an aryl-carbonyl)amino group (e.g., N-benzoyl-N-methylamino).

[0044] In this specification, an example of an optionally substituted carbamoyl group is an optionally substituted C group having 1 to 3 substituents each optionally selected from substituent group A. 1-6 Alkyl 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, 5-14 member aromatic heterocyclylcarbonyl group, 3-14 member non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl groups, 5-14 member aromatic heterocyclic groups, carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl groups and mono- or di-C 7-16 The carbamoyl group comprises one or two substituents selected from aralkyl-carbamoyl groups. Examples of carbamoyl groups that are preferably substituted include carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 2-6 Alkenyl-carbamoyl group (e.g., diallylcarbamoyl), mono- or di-C 3-10 Cycloalkyl-carbamoyl groups (e.g., cyclopropylcarbamoyl, cyclohexylcarbamoyl), mono- or di-C 6-14 Aryl-carbamoyl group (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 contains an aryl-carbonyl-carbamoyl group (e.g., benzoylcarbamoyl) and a 5-14 member aromatic heterocyclylcarbamoyl group (e.g., pyridylcarbamoyl).

[0045] In this specification, an example of an optionally substituted thiocarbamoyl group is an optionally substituted C group having 1 to 3 substituents each optionally selected from substituent group A. 1-6 Alkyl 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, 5-14 member aromatic heterocyclylcarbonyl group, 3-14 member non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl groups, 5-14 member aromatic heterocyclic groups, carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl groups and mono- or di-C 7-16 The thiocarbamoyl group comprises one or two substituents selected from aralkyl-carbamoyl groups. Examples of thiocarbamoyl groups that are preferably substituted 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 group (e.g., diallylthiocarbamoyl), mono- or di-C 3-10 Cycloalkyl-thiocarbamoyl groups (e.g., cyclopropylthiocarbamoyl, cyclohexylthiocarbamoyl), mono- or di-C 6-14 Aryl-thiocarbamoyl group (e.g., phenylthiocarbamoyl), mono- or di-C 7-16 Aralkyl-thiocarbamoyl group (e.g., benzylthiocarbamoyl, phenethylthiocarbamoyl), mono- or di-C 1-6 Alkyl-carbonyl-thiocarbamoyl groups (e.g., acetylthiocarbamoyl, propionylthiocarbamoyl), mono- or di-C 6-14It contains an aryl-carbonyl-thiocarbamoyl group (e.g., benzoylthiocarbamoyl) and a 5-14 member aromatic heterocyclylthiocarbamoyl group (e.g., pyridylthiocarbamoyl).

[0046] In this specification, an example of an optionally substituted sulfamoyl group is an optionally substituted C group having 1 to 3 substituents each optionally selected from substituent group A. 1-6 Alkyl 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, 5-14 member aromatic heterocyclylcarbonyl group, 3-14 member non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl groups, 5-14 member aromatic heterocyclic groups, carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl groups and mono- or di-C 7-16 The material contains a sulfamoyl group having one or two substituents selected from aralkyl-carbamoyl groups. Examples of sulfamoyl groups that are preferably substituted 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 group (e.g., diallyl sulfamoyl), mono- or di-C 3-10 Cycloalkyl-sulfamoyl groups (e.g., cyclopropylsulfamoyl, cyclohexylsulfamoyl), mono- or di-C 6-14 Aryl-sulfamoyl group (e.g., phenylsulfamoyl), mono- or di-C 7-16 Aralkyl sulfamoyl groups (e.g., benzyl sulfamoyl, phenethyl sulfamoyl), mono- or di-C1-6 Alkyl-carbonyl-sulfamoyl groups (e.g., acetylsulfamoyl, propionylsulfamoyl), mono- or di-C 6-14 It contains an aryl-carbonyl-sulfamoyl group (e.g., benzoylsulfamoyl) and a 5-14 member aromatic heterocyclylsulfamoyl group (e.g., pyridylsulfamoyl).

[0047] In this specification, an example of an "optionally substituted hydroxyl group" is an example of a "C" having one to three substituents selected from substituent group A, respectively. 1-6 Alkyl 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, 5-14 member aromatic heterocyclylcarbonyl group, 3-14 member non-aromatic heterocyclylcarbonyl group, C 1-6 Alkoxy-carbonyl groups, 5-14 member aromatic heterocyclic groups, carbamoyl groups, mono- or di-C 1-6 Alkyl-carbamoyl group, mono- or di-C 7-16 Aralkyl-carbamoyl group, C 1-6 Alkyl sulfonyl group and C 6-14 It contains a hydroxyl group having one substituent selected from arylsulfonyl groups. Examples of hydroxyl groups that are preferably substituted include hydroxyl groups, C 1-6 Alkoxy group, C 2-6 Alkenyloxy groups (e.g., allyloxy, 2-butenyloxy, 2-pentenyloxy, 3-hexenyloxy), C 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), C 6-14 Aryloxy group (e.g., phenoxy, naphthyloxy), C 7-16 Aralkyloxy group (e.g., benzyloxy, phenethyloxy), C 1-6Alkyl-carbonyloxy groups (e.g., acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pivaloyloxy), C 6-14 Aryl-carbonyloxy group (e.g., benzoyloxy), C 7-16 Aalkyl-carbonyloxy group (e.g., benzylcarbonyloxy), 5-14 member aromatic heterocyclylcarbonyloxy group (e.g., nicotinoyloxy), 3-14 member non-aromatic heterocyclylcarbonyloxy group (e.g., piperidinylcarbonyloxy), C 1-6 Alkoxy-carbonyloxy groups (e.g., tert-butoxycarbonyloxy), 5-14 member aromatic heterocyclyloxy groups (e.g., pyridyloxy), carbamoyloxy groups, C 1-6 Alkyl-carbamoyloxy group (e.g., methylcarbamoyloxy), C 7-16 Aralkyl-carbamoyloxy group (e.g., benzylcarbamoyloxy), C 1-6 Alkyl sulfonyloxy groups (e.g., methyl sulfonyloxy, ethyl sulfonyloxy) and C 6-14 It contains an aryl sulfonyloxy group (e.g., phenylsulfonyloxy).

[0048] In this specification, an example of an optionally substituted sulfanyl group is an optionally substituted C group having 1 to 3 substituents each optionally selected from substituent group A. 1-6 Alkyl 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 The compound comprises a sulfanyl group having one substituent selected from an aryl-carbonyl group and a 5-14 member aromatic heterocyclic group, and a halogenated sulfanyl group. Examples of sulfanyl groups that are preferably substituted include sulfanyl(-SH) groups and C 1-6 Alkylthio group, C 2-6Alkenylthio groups (e.g., allylthio, 2-butenylthio, 2-pentenylthio, 3-hexenylthio), C 3-10 Cycloalkylthio group (e.g., cyclohexylthio), C 6-14 Arylthio group (e.g., phenylthio, naphthylthio), C 7-16 Aralkylthio group (e.g., benzylthio, phenethylthio), C 1-6 Alkyl-carbonylthio group (e.g., acetylthio, propionylthio, butyrylthio, isobutylylthio, pivaloylthio), C 6-14 It includes aryl-carbonylthio groups (e.g., benzoylthio), 5-14 member aromatic heterocyclylthio groups (e.g., pyridylthio), and halogenated thio groups (e.g., pentafluorothio).

[0049] In this specification, an example of an "optionally substituted silyl group" is an example of a "C" having 1 to 3 substituents each optionally selected from substituent group A. 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 3-10 Cycloalkyl groups, C 6-14 Aryl group and C 7-16 It contains a silyl group having 1 to 3 substituents selected from aralkyl groups. Examples of silyl groups that are preferably substituted include tri-C 1-6 Contains alkylsilyl groups (e.g., trimethylsilyl, tert-butyl(dimethyl)silyl).

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

[0051] In this specification, examples of “aromatic heterocycles” include 5-14 membered (preferably 5-10 membered) aromatic heterocycles that, in addition to carbon atoms, contain 1-4 heteroatoms selected from nitrogen, sulfur, and oxygen atoms as ring constituent atoms. Preferred examples of “aromatic heterocycles” are 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, triazine, and 8-14 member condensed polycyclic (preferably bicyclic or tricyclic) aromatic heterocycles, such as benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzotriazole, imidazopyridine, thienopyridine, phlopyridine, pyrrolopyridine, pyrazolopyridine, oxazolopyridine, thiazolopyridine, imidazopyrazine, imidazopyrimidine, thienopyrimidine, phlopyrimidine, pyrrolo This includes pyrimidines, pyrazolopyrimidines, oxazolopyrimidines, thiazolopyrimidines, pyrazolotriazines, naphtho[2,3-b]thiophene, phenoxatiin, indole, isoindole, 1H-indazole, purines, isoquinoline, quinoline, phthalazines, naphthyridines, quinoxaline, quinazoline, cinnoline, carbazoles, β-carbolin, phenanthidines, acridines, phenazines, phenothiazines, phenoxazines, and others.

[0052] In this specification, examples of "non-aromatic heterocycles" include 3-14 member (preferably 4-10 member) non-aromatic heterocycles that, in addition to carbon atoms, contain 1-4 heteroatoms selected from nitrogen, sulfur, and oxygen atoms as ring constituent atoms. Examples of preferred "non-aromatic heterocycles" include 3- to 8-membered monocyclic non-aromatic heterocycles, such as aziridine, oxirane, thiirane, azetidine, oxetane, thietan, tetrahydrothiophene, tetrahydrofuran, pyrroline, pyrrolidine, imidazoline, imidazolidine, oxazoline, oxazolidine, pyrazolline, pyrazolidine, thiazoline, thiazolidin, tetrahydroisothiazole, tetrahydrooxazole, tetrahydroisoxazole, piperidine, piperazine, tetrahydropyridine, dihydropyridine, dihydrothiopyran, tetrahydropyrimidine, tetrahydropyridazine, dihydropyran, tetrahydropyran, tetrahydrothiopyran, morpholine, thiomorpholine, azepan, diazepan, azepine, azocan, diazocan, oxepan, etc.; and This includes 9-14 membered condensed polycyclic (preferably bicyclic or tricyclic) non-aromatic heterocycles, such as dihydrobenzofuran, dihydrobenzimidazole, dihydrobenzoxazole, dihydrobenzothiazole, dihydrobenzisothiazole, dihydronaphtho[2,3-b]thiophene, tetrahydroisoquinoline, tetrahydroquinoline, 4H-quinolidine, indoline, isoindoline, tetrahydrothieno[2,3-c]pyridine, tetrahydrobenzazepine, tetrahydroquinoxaline, tetrahydrophenanthidine, hexahydrophenothiazine, hexahydrophenoxazine, tetrahydrophthalazine, tetrahydronaphthyridine, tetrahydroquinazoline, tetrahydrocinnoline, tetrahydrocarbazole, tetrahydro-β-carbolin, tetrahydroacridine, tetrahydrophenazine, tetrahydrothioxanthene, octahydroisoquinoline, and the like. In this specification, an example of a "nitrogen-containing heterocycle" includes a "heterocycle" that contains at least one nitrogen atom as a ring constituent atom. In this specification, "C 6-14An example of an aromatic hydrocarbon ring is the above "C 6-14 In addition to examples of "aromatic hydrocarbon rings," this includes anthracene, phenanthrene, and acenaphthylene.

[0053] The definitions of each symbol in equation (I) are explained in detail below.

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

[0055] X 2 , X 3 and X 4 Each is independently either 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 And here, R X5 It is a hydrogen atom. X 5 It is preferably N.

[0057] X 6 is N or CR X6 And here, R X6 It is a hydrogen atom. X 6 It is preferably CH.

[0058] formula: [ka] The substructures represented by are, in particular, formulas (Ia), (Ib), or (Ic): [ka] [In the formula, each symbol is defined as above.] It is represented by [this].

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

[0060] formula [ka] The substructure represented by is more preferably by formula (Ia1), (Ib1), (Ic1), or (Ib2): [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by, More preferably, formulas (Ia1), (Ib1), or (Ic1): [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by [this].

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

[0062] formula [ka] The substructure represented by formula (IIa1), (IIb1), (IIc1), or (IIb2) is more preferably formula (IIa1), (IIb1), (IIc1), or (IIb2): [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by, More preferably, formulas (IIa1), (IIb1), or (IIc1): [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by [this].

[0063] formula [ka] The substructure represented by formula (IIIa), (IIIb), or (IIIc) is particularly preferred: [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by [this].

[0064] Y 1 is N or CR Y1 And here, R Y1 It is a hydrogen atom. Y 1 It is preferably CH.

[0065] Y 2 is N or CR Y2 And here, R Y2 These are hydrogen atoms, halogen atoms (e.g., fluorine atoms, chlorine atoms), or cyano groups. Y 2 Preferably N or CR Y2 And here, R Y2 is a hydrogen atom or a halogen atom (e.g., a fluorine atom, a chlorine atom), more preferably CH or CF, and particularly preferably CF.

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

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

[0068] formula [ka] The substructure represented by equations (Ar-1) to (Ar-12) is particularly: [ka] [In the formula, each symbol is defined as above.] It is represented by [this]. Y 1 , Y 2 , Y 3 and Y 4 If all of them are C, then the substructure is represented by equation (Ar-1). Y 1 , Y 2 , Y 3 and Y 4 If at least one of them is N, then the substructure is represented by equations (Ar-2) to (Ar-12). Collectively, these substructures are represented by equation: [ka] [During the ceremony, Y 1a is N or CR Y1a And here, R Y1a is a hydrogen atom; Y 2a is N or CR Y2a And here, R Y2a is a hydrogen atom or a halogen atom (for example, a fluorine atom); Y 3a is N or CR Y3a And here, R Y3a is a hydrogen atom; Y 4a is N or CR Y4a And here, R Y4a is a hydrogen atom; and Y 1a , Y 2a , Y 3a and Y 4a At least one of them is N. It is represented by [this]. Y 1a It is preferably N. Y 2a It is preferably CH. Y 3a It is preferably CH. Y 4a It is preferably CH.

[0069] formula [ka] The substructure represented by formulas (Ar-1) to (Ar-11) is preferably: [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by [this]. In this embodiment, R Y1 It is a hydrogen atom. In this embodiment, R Y2 The group is a hydrogen atom, a halogen atom (e.g., a fluorine atom, a chlorine atom), or a cyano group, preferably a hydrogen atom or a halogen atom (e.g., 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 This is a hydrogen atom or a halogen atom (for example, a fluorine atom), preferably a hydrogen atom. In this embodiment, R Y4 This is a hydrogen atom or a halogen atom (for example, a fluorine atom), preferably a hydrogen atom.

[0070] formula [ka] The substructure represented by formula (Ar-1) or (Ar-2) is more preferably formula (Ar-1) or (Ar-2): [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by, More preferably, formula (Ar-1-1) or (Ar-2-1): [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by [this]. In this embodiment, R Y2 The group is a hydrogen atom, a halogen atom (e.g., a fluorine atom, a chlorine atom), or a cyano group, preferably a hydrogen atom or a halogen atom (e.g., 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 substructure represented by formula (Ar-1-1) is particularly preferred. [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by [this]. In this embodiment, R Y2 The group is a hydrogen atom, a halogen atom (e.g., a fluorine atom, a chlorine atom), or a cyano group, preferably a hydrogen atom or a halogen atom (e.g., a fluorine atom, a chlorine atom), more preferably a halogen atom (e.g., a fluorine atom, a chlorine atom), and particularly preferably a fluorine atom.

[0072] Ring A 1 C is sometimes further replaced 6-14 Aromatic hydrocarbons, optionally further substituted aromatic heterocycles, or optionally further substituted non-aromatic heterocycles, each optionally fused with an optionally substituted five-membered or six-membered ring.

[0073] "C may be further substituted in some cases" 6-14 "C" of "aromatic hydrocarbons" 6-14 The "aromatic hydrocarbon" is preferably a benzene ring. The "aromatic heteroring" in "aromatic heteroring that may be further substituted" is preferably a 5-membered or 6-membered aromatic heteroring. The "non-aromatic heteroring" in "a non-aromatic heteroring that may be further substituted" is preferably a 5-membered or 6-membered non-aromatic heteroring.

[0074] Examples of "five-membered or six-membered rings that are substituted in some cases" include benzene rings, C 5-6 This includes cycloalkenes, 5-membered or 6-membered aromatic heterocycles, and 5-membered or 6-membered non-aromatic heterocycles.

[0075] "C may be further substituted in some cases" 6-14 "C" of "aromatic hydrocarbons" 6-14 The "aromatic heterocycle" in "aromatic heterocycles that may be further substituted," the "non-aromatic heterocycle" in "non-aromatic heterocycles that may be further substituted," and the "five-membered or six-membered ring" in "five-membered or six-membered rings that may be further substituted" are defined by the formula: [ka] In addition to the substructure represented by, it may optionally have 1 to 5 (preferably 1 to 3) substituents at appropriate positions.

[0076] Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds two, each substituent may be the same or different. Furthermore, substituent group A may be substituted with substituents selected from substituent group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, each substituent may be the same or different.

[0077] Ring A 1 Preferably ring A 2That is, a benzene ring which may be further substituted, a five- or six-membered aromatic heteroring which may be further substituted, or a five- or six-membered non-aromatic heteroring which may be further substituted, each of which is optionally fused with a five- or six-membered ring which may be substituted.

[0078] The "five-membered or six-membered aromatic heteroring" in "a five-membered or six-membered aromatic heteroring that may be further substituted" is preferably a pyridine ring (which may be 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 "five-membered or six-membered non-aromatic heteroring" in "a five-membered or six-membered non-aromatic heteroring that may be further substituted" is preferably a dihydropyridine ring or a dihydropyrimidine ring.

[0079] Examples of "five-membered or six-membered rings that are substituted in some cases" include benzene rings, C 5-6 This includes cycloalkenes, 5-membered or 6-membered aromatic heterocycles, and 5-membered or 6-membered non-aromatic heterocycles.

[0080] The "benzene ring" in "a benzene ring that may be further substituted," the "5-membered or 6-membered aromatic heteroring" in "a 5-membered or 6-membered aromatic heteroring that may be further substituted," the "5-membered or 6-membered non-aromatic heteroring" in "a 5-membered or 6-membered non-aromatic heteroring that may be further substituted," and the "5-membered or 6-membered ring" in "a 5-membered or 6-membered ring that may be further substituted" are defined by formula: [ka] In addition to the substructure represented by, it may optionally have 1 to 5 (preferably 1 to 3) substituents at appropriate positions.

[0081] Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds two, each substituent may be the same or different. Furthermore, substituent group A may be substituted with substituents selected from substituent group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, each substituent may be the same or different.

[0082] Ring A 2 Preferably (1) Benzene ring [In some cases, it is condensed with a 5-6 membered monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the condensed ring is dihydrobenzofuran, isoindoline), and in some cases, it is substituted with 1-3 substituents selected from (a) and (b), (a) Oxo group and (b) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (aa). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) Formyl group, (f) amino group, (g) Carbamoyl group, (h) C which is substituted with 1 to 3 substituents selected from (i) to (v) depending on the case. 1-6 Alkyl alkyl groups (e.g., methyl, ethyl, isopropyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Hydroxyl 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) G-C 1-6 Alkylsulfinylideneamino group (e.g., N-dimethylsulfinylideneamino) (I C 2-6 Alkenyl group (e.g., vinyl), (j) C 2-6 Alkynyl group (e.g., ethynyl), (k) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino) (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (l) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (m) C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (o) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino), (p) Mono- or di-C12, which may be substituted with 1 to 3 substituents selected from (i) to (ix) as applicable. 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) Hydroxyl 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 group (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 group (e.g., phenyl), (viii) Five-membered or six-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group substituted with 1-3 substituents selected from (I) to (III) as applicable (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxide thiomorpholinyl, tetrahydropyranyl) (I) Hydroxyl group, (II) Oxo group and (III) C 1-6 Alkyl group (e.g., methyl) (q) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (r) C which is substituted with 1 to 3 substituents selected from (i) in some cases. 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy) (i) Depending on the case, 1 to 3 C 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 group (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 Aryl-carbamoyl group (e.g., phenylcarbamoyl), (u) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl, piperazinyl) substituted with alkyl-carbonyl groups (e.g., acetyl), (v) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (w) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl, piperidyl carbonyl, morpholinyl carbonyl) which may be substituted with 1-3 substituents selected from (i) to (v) depending on the case. (i) Hydroxyl 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 groups (e.g., morpholinyl) (x) 9-14 membered bicyclic non-aromatic heterocyclyl carbonyl group (e.g., tetrahydroimidazopyradinylcarbonyltetrahydrotriazolopyradinylcarbonyl), (y) Depending on the case, 1 to 3 C 1-6 A 5-membered or 6-membered monocyclic aromatic heterocyclylcarbamoyl group substituted with an alkyl group (e.g., methyl) (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl), (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group substituted with 1-3 substituents selected from (i) to (iv) as applicable (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl) (i) 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) 3-8 member monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Five-membered or six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (n). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Carboxy group, (d) amino group, (e) Carbamoyl group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (vii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Hydroxyl group, (iv) Carboxy group, (v) C 1-6 Alkoxy groups (e.g., methoxy), (vi) C 7-16 Aralkyloxycarbonyl group (e.g., benzyloxycarbonyl), (vii) Mono- or di-C atoms substituted with 1 to 3 substituents selected from (I) to (II), depending on the case. 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 groups (e.g., morpholinyl) (g) C which is substituted with 1 to 3 substituents selected from (i) to (iv) depending on the case. 1-6Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) C 1-6 Alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (h) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (I C 1-6 Alkyl-carbonyl group (e.g., acetyl), (j) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl), (k) Mono- or di-C atoms that are substituted in some cases 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 atoms substituted with 1 to 3 substituents selected from (I) to (II) as applicable. 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 group (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) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) Five-membered or six-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) [In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (d)] (a) Oxo group, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C which may be substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) Halogen atoms (e.g., fluorine atoms), (II) Cyano group and (III) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 [Alkoxy groups (e.g., methoxy, ethoxy)] That is the case.

[0083] In other embodiments, ring A 2 Preferably (1) Benzene ring [In some cases, it is condensed with a 5-6 member monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the condensed ring is dihydrobenzofuran, isoindoline), and in some cases it is substituted with 1-3 substituents selected from (a)-(b)] (a) Oxo group and (b) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (aa). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) Formyl group, (f) amino group, (g) Carbamoyl group, (h) C which is substituted with 1 to 3 substituents selected from (i) to (iv) depending on the case. 1-6 Alkyl alkyl groups (e.g., methyl, ethyl, isopropyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Hydroxyl group, (iii) mono- or di-C 1-6 Alkylamino groups (e.g., N,N-dimethylamino) and (iv) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (I C 2-6 Alkenyl group (e.g., vinyl), (j) C 2-6 Alkynyl group (e.g., ethynyl), (k) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (l) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (m) C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (o) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino), (p) Mono- or di-C12, which may be substituted with 1 to 3 substituents selected from (i) to (ix) as applicable. 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) Hydroxyl 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 group (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 group (e.g., phenyl), (viii) Five-membered or six-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group substituted with 1-3 substituents selected from (I) to (III) as applicable (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxide thiomorpholinyl, tetrahydropyranyl) (I) Hydroxyl group, (II) Oxo group and (III) C 1-6 Alkyl group (e.g., methyl) (q) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (r) C which is substituted with 1 to 3 substituents selected from (i) in some cases. 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy) (i) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) substituted with alkyl groups (e.g., methyl) (s) C 3-10 Cycloalkylsulfonyl-carbamoyl group (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 Aryl-carbamoyl group (e.g., phenylcarbamoyl), (u) Depending on the case, 1 to 3 C 1-63- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl, piperazinyl) substituted with alkyl-carbonyl groups (e.g., acetyl), (v) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (w) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl, piperidyl carbonyl, morpholinyl carbonyl) which may be substituted with 1-3 substituents selected from (i) to (v) depending on the case. (i) Hydroxyl 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 groups (e.g., morpholinyl) (x) 9-14 membered bicyclic non-aromatic heterocyclyl carbonyl group (e.g., tetrahydroimidazopyradinylcarbonyltetrahydrotriazolopyradinylcarbonyl), (y) Depending on the case, 1 to 3 C 1-6 A 5-membered or 6-membered monocyclic aromatic heterocyclylcarbamoyl group substituted with an alkyl group (e.g., methyl) (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl), (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group substituted with 1-3 substituents selected from (i) to (iv) as applicable (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl) (i) 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) 3-8 member monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Five-membered or six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (n). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Carboxy group, (d) amino group, (e) Carbamoyl group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (viii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Hydroxyl group, (iv) Carboxy group, (v) C 1-6 Alkoxy groups (e.g., methoxy), (vi) C 7-16 Aralkyloxycarbonyl group (e.g., benzyloxycarbonyl), (vii) Mono- or di-C atoms substituted with 1 to 3 substituents selected from (I) to (II), depending on the case. 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 groups (e.g., morpholinyl) (g) C which is substituted with 1 to 3 substituents selected from (i) to (iv) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) C 1-6 Alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (h) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (I C 1-6 Alkyl-carbonyl group (e.g., acetyl), (j) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl), (k) Mono- or di-C atoms that are substituted in some cases 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 atoms substituted with 1 to 3 substituents selected from (I) to (II) as applicable. 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 group (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) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) Five-membered or six-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) [In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (d)] (a) Oxo group, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C which may be substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) Halogen atoms (e.g., fluorine atoms), (II) Cyano group and (III) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 [Alkoxy groups (e.g., methoxy, ethoxy)] That is the case.

[0084] In other embodiments, ring A 2 Preferably (1) A benzene ring which is optionally further substituted with 1 to 5 substituents selected from (a) to (d) (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl group (e.g., methyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (d) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6Alkoxy groups (e.g., methoxy), (2) Five-membered or six-membered aromatic heterocycles which may be further substituted with one to four substituents selected from (a) to (c) (e.g., pyridine (may be oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan) (a) cyano group, (b) C which may be 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 five-membered or six-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) which may be further substituted with one to four substituents selected from (a) to (c) as applicable. (a) Oxo group, (b) Cyano group and (c) C 1-6 Alkyl group (e.g., methyl) That is the case.

[0085] Ring A 2 is more (1) Benzene ring [In some cases, it is condensed with a 5-6 member monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the condensed ring is dihydrobenzofuran, isoindoline), and in some cases it is substituted with 1-3 substituents selected from (a)-(b)] (a) Oxo group and (b) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (aa). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) Formyl group, (f) amino group, (g) Carbamoyl group, (h) C which is substituted with 1 to 3 substituents selected from (i) to (v) depending on the case. 1-6 Alkyl alkyl groups (e.g., methyl, ethyl, isopropyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Hydroxyl 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) G-C 1-6 Alkylsulfinylideneamino group (e.g., N-dimethylsulfinylideneamino) (I C 2-6 Alkenyl group (e.g., vinyl), (j) C 2-6 Alkynyl group (e.g., ethynyl), (k) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (l) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (m) C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (o) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino), (p) Mono- or di-C12, which may be substituted with 1 to 3 substituents selected from (i) to (ix) as applicable. 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) Hydroxyl 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 group (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 group (e.g., phenyl), (viii) Five-membered or six-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group substituted with 1-3 substituents selected from (I) to (III) as applicable (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxide thiomorpholinyl, tetrahydropyranyl) (I) Hydroxyl group, (II) Oxo group and (III) C 1-6 Alkyl group (e.g., methyl) (q) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (r) C which is substituted with 1 to 3 substituents selected from (i) in some cases. 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy) (i) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) substituted with alkyl groups (e.g., methyl) (s) C 3-10Cycloalkylsulfonyl-carbamoyl group (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 Aryl-carbamoyl group (e.g., phenylcarbamoyl), (u) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl, piperazinyl) substituted with alkyl-carbonyl groups (e.g., acetyl), (v) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (w) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl, piperidyl carbonyl, morpholinyl carbonyl) which may be substituted with 1-3 substituents selected from (i) to (v) depending on the case. (i) Hydroxyl 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 groups (e.g., morpholinyl) (x) 9-14 membered bicyclic non-aromatic heterocyclyl carbonyl group (e.g., tetrahydroimidazopyradinylcarbonyltetrahydrotriazolopyradinylcarbonyl), (y) Depending on the case, 1 to 3 C 1-6 A 5-membered or 6-membered monocyclic aromatic heterocyclylcarbamoyl group substituted with an alkyl group (e.g., methyl) (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl), (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group substituted with 1-3 substituents selected from (i) to (iv) as applicable (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl) (i) 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) 3-8 member monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Pyridine ring (which may be oxidized) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (m). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Amino group, (d) Carbamoyl group, (e) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (f) C which is substituted with 1 to 3 substituents selected from (i) to (iv) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) C 1-6 Alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (g) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl group (e.g., methoxycarbonyl), (j) Mono- or di-C atoms which may be 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) Depending on the case, 1 to 3 mono- or di-C 1-6 Mono- or di-C molecules 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) 3-8 membered monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring which may be further substituted with 1 to 3 substituents selected from (a) to (d) in some cases. (a) cyano group, (b) amino group, (c) C 1-6 Alkoxy groups (e.g., methoxy, ethoxy) and (d) Mono- or di-C 1-6 Alkylamino group (e.g., N,N-dimethylamino), (4) A pyridazine ring which may be further substituted with 1 to 3 cyano groups. (5) A pyrazine ring which may be further substituted with 1 to 3 substituents selected from (a) to (c) in some cases. (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 which may be further substituted with 1 to 3 substituents selected from (a) to (c) as applicable. (a) cyano group, (b) Carboxy group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (viii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Hydroxyl group, (iv) Carboxy group, (v) C 1-6 Alkoxy groups (e.g., methoxy), (vi) C 7-16 Aralkyloxycarbonyl group (e.g., benzyloxycarbonyl), (vii) Mono- or di-C atoms substituted with 1 to 3 substituents selected from (I) to (II), depending on the case. 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 groups (e.g., morpholinyl) (d) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkoxycarbonyl groups (e.g., propoxycarbonyl, tert-butoxycarbonyl) and (e) 1 to 3 C depending on the case 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl), (7) An imidazole ring which may be further substituted with 1 to 3 substituents selected from (a) to (b) as applicable. (a) Cyano group and (b) C 1-6 Alkyl groups (e.g., methyl), (8) Depending on the case, one or two more C 1-6 Thiazole rings substituted with alkyl groups (e.g., methyl), (9) A thiophene ring which may be further substituted with 1 to 3 substituents selected from (a) to (d) in some cases. (a) cyano group, (b) Carboxy group, (c) C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl) and (d) Mono- or di-C 1-6 Alkyl-carbamoyl group (e.g., N-methylcarbamoyl), (10) Furan ring, (11) A dihydropyridine ring which may be further substituted with 1 to 4 substituents selected from (a) to (d) as applicable. (a) cyano group, (b) Oxo group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C which may be substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) Halogen atoms (e.g., fluorine atoms), (II) Cyano group and (III) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) or (12) A dihydropyrimidine ring which is optionally further substituted with 1 to 4 substituents selected from (a) to (b) (a) Cyano group and (b) Oxo group That is the case.

[0086] In other embodiments, ring A 2 is more (1) Benzene ring [In some cases, it is condensed with a 5-6 member monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the condensed ring is dihydrobenzofuran, isoindoline), and in some cases it is substituted with 1-3 substituents selected from (a)-(b)] (a) Oxo group and (b) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (aa). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) Formyl group, (f) amino group, (g) Carbamoyl group, (h) C which is substituted with 1 to 3 substituents selected from (i) to (iv) depending on the case. 1-6 Alkyl alkyl groups (e.g., methyl, ethyl, isopropyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Hydroxyl group, (iii) mono- or di-C 1-6 Alkylamino groups (e.g., N,N-dimethylamino) and (iv) G-C 1-6 Alkylsulfinylideneamino group (e.g., N-dimethylsulfinylideneamino) (I C 2-6 Alkenyl group (e.g., vinyl), (j) C 2-6 Alkynyl group (e.g., ethynyl), (k) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (l) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (m) C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) Depending on the case, 1 to 3 C1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (o) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino), (p) Mono- or di-C12, which may be substituted with 1 to 3 substituents selected from (i) to (ix) as applicable. 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) Hydroxyl 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 group (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 group (e.g., phenyl), (viii) Five-membered or six-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group substituted with 1-3 substituents selected from (I) to (III) as applicable (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxide thiomorpholinyl, tetrahydropyranyl) (I) Hydroxyl group, (II) Oxo group and (III) C 1-6 Alkyl group (e.g., methyl) (q) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (r) C which is substituted with 1 to 3 substituents selected from (i) in some cases. 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy) (i) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) substituted with alkyl groups (e.g., methyl) (s) C 3-10 Cycloalkylsulfonyl-carbamoyl group (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 Aryl-carbamoyl group (e.g., phenylcarbamoyl), (u) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl, piperazinyl) substituted with alkyl-carbonyl groups (e.g., acetyl), (v) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (w) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl, piperidyl carbonyl, morpholinyl carbonyl) which may be substituted with 1-3 substituents selected from (i) to (v) depending on the case. (i) Hydroxyl 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 groups (e.g., morpholinyl) (x) 9-14 membered bicyclic non-aromatic heterocyclyl carbonyl group (e.g., tetrahydroimidazopyradinylcarbonyltetrahydrotriazolopyradinylcarbonyl), (y) Depending on the case, 1 to 3 C 1-6 A 5-membered or 6-membered monocyclic aromatic heterocyclylcarbamoyl group substituted with an alkyl group (e.g., methyl) (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl), (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group substituted with 1-3 substituents selected from (i) to (iv) as applicable (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl) (i) 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) 3-8 member monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Pyridine ring (which may be oxidized) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (m). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Amino group, (d) Carbamoyl group, (e) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (f) C which is substituted with 1 to 3 substituents selected from (i) to (iv) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) C 1-6 Alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (g) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl group (e.g., methoxycarbonyl), (j) Mono- or di-C atoms which may be 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) Depending on the case, 1 to 3 mono- or di-C 1-6 Mono- or di-C molecules 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) 3-8 membered monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring which may be further substituted with 1 to 3 substituents selected from (a) to (d) in some cases. (a) cyano group, (b) amino group, (c) C 1-6 Alkoxy groups (e.g., methoxy, ethoxy) and (d) Mono- or di-C 1-6 Alkylamino group (e.g., N,N-dimethylamino), (4) A pyridazine ring which may be further substituted with 1 to 3 cyano groups. (5) A pyrazine ring which may be further substituted with 1 to 3 substituents selected from (a) to (c) in some cases. (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 which may be further substituted with 1 to 3 substituents selected from (a) to (e) as applicable. (a) cyano group, (b) Carboxylic groups substituted with 1 to 3 substituents selected from (i) to (viii) as applicable. (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Hydroxyl group, (iv) Carboxy group, (v) C 1-6 Alkoxy groups (e.g., methoxy), (vi) C 7-16 Aralkyloxycarbonyl group (e.g., benzyloxycarbonyl), (vii) Mono- or di-C atoms substituted with 1 to 3 substituents selected from (I) to (II), depending on the case. 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 groups (e.g., morpholinyl), (c) C 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (d) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkoxycarbonyl groups (e.g., propoxycarbonyl, tert-butoxycarbonyl) and (e) 1 to 3 C depending on the case 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbamoyl groups (e.g., N-methylcarbamoyl, N,N-dimethylcarbamoyl, N-ethylcarbamoyl), (7) An imidazole ring which may be further substituted with 1 to 3 substituents selected from (a) to (b) as applicable. (a) Cyano group and (b) C 1-6 Alkyl groups (e.g., methyl), (8) Depending on the case, one or two more C 1-6 Thiazole rings substituted with alkyl groups (e.g., methyl), (9) A thiophene ring which may be further substituted with 1 to 3 substituents selected from (a) to (d) in some cases. (a) cyano group, (b) Carboxy group, (c) C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl) and (d) Mono- or di-C 1-6 Alkyl-carbamoyl group (e.g., N-methylcarbamoyl), (10) Furan ring, (11) A dihydropyridine ring which may be further substituted with 1 to 4 substituents selected from (a) to (d) as applicable. (a) cyano group, (b) Oxo group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C which may be substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) Halogen atoms (e.g., fluorine atoms), (II) Cyano group and (III) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy, ethoxy) or (12) A dihydropyrimidine ring which is optionally further substituted with 1 to 4 substituents selected from (a) to (b) (a) Cyano group and (b) Oxo group That is the case.

[0087] In other embodiments, ring A 2 is more (1) A benzene ring which is optionally further substituted with 1 to 5 substituents selected from (a) to (d) (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl group (e.g., methyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (d) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy), (2) A pyridine ring (which may be oxidized) which may be further substituted with 1 to 4 substituents selected from (a) to (c) as applicable. (a) cyano group, (b) C which may be 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 which may be further substituted with 1 to 3 substituents selected from (a) to (b) as applicable. (a) Cyano group and (b) C 1-6 alkoxy group (e.g., methoxy) or (4) A dihydropyridine ring which may be further substituted with 1 to 4 substituents selected from (a) to (b) as applicable. (a) cyano group, (b) Oxo group and (b) C 1-6 It is an alkyl group (for example, methyl).

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

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

[0090] "Benzene ring," "6-membered aromatic heterocycle," and "6-membered non-aromatic heterocycle" are defined by the formula: [ka] In addition to the substructure represented by , it has one cyano group and optionally 1 to 5 (preferably 1 to 3) substituents at substitutable positions.

[0091] Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds two, each substituent may be the same or different. Furthermore, substituent group A may be substituted with substituents selected from substituent group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, each substituent may be the same or different.

[0092] Ring A 2 is more (1) Benzene ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (q). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (ii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (k) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), Furthermore, it is substituted with one cyano group, and In some cases, it is further substituted with 1 to 4 substituents selected from (a) to (h). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) Six-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) That is the case.

[0093] In other embodiments, ring A 2 is more (1) Benzene ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (q). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl (e.g., methyl, ethyl) field, (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (k) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), Furthermore, it is substituted with one cyano group, and In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (i). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) Six-membered non-aromatic heterocycles (e.g., dihydropyridine, dihydropyrimidine) Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) That is the case.

[0094] In other embodiments, ring A 2 is more (1) Benzene ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (c). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl group (e.g., methyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (c) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 [alkoxy group (e.g., methoxy)] (2) Six-membered aromatic heterocycles (e.g., pyridine, pyrimidine) [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) C which may be 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) Six-membered non-aromatic heterocycles (e.g., dihydropyridine) [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) Oxo group and (b) C 1-6 Alkyl groups (e.g., methyl) That is the case.

[0095] Ring A 2 Even more (1) Benzene ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (q). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (ii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (k) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6Alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Pyridine ring (which may be oxidized) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), Furthermore, it is substituted with one cyano group, and In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (i). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (3) Pyrimidine ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 3 substituents selected from (a) to (c). (a) amino group, (b) C 1-6 Alkoxy groups (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 Alkylamino group (e.g., N,N-dimethylamino), (4) A pyridazine ring that is further substituted with one cyano group, (5) Pyrazine ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 3 substituents selected from (a) to (b). (a) C 1-6 Alkyl groups (e.g., methyl) and (b) C 1-6 [alkoxy group (e.g., methoxy)] (6) Dihydropyridine ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) or (7) Dihydropyrimidine ring Furthermore, it is substituted with one cyano group, and In some cases, it is further substituted with one or two oxo groups. That is the case.

[0096] In other embodiments, ring A 2 Even more (1) Benzene ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (q). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl (e.g., methyl, ethyl) field, (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6an alkylamino group (e.g., N-ethylamino), (k) optionally, a mono- or di-C 1-6 alkyl group substituted with 1 to 3 C 1-6 alkoxy groups (e.g., methoxy), (l) optionally, a mono- or di-C 1-6 alkyl group substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl), (m) a di-C 1-6 alkylsulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) optionally, a C 1-6 alkyl group (e.g., methyl) substituted with 1 to 3 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) substituted with 1 to 3 C 3-10 cycloalkyloxy group (e.g., cyclohexyloxy), (o) optionally, a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyl-oxy) substituted with 1 to 3 oxo groups, (p) optionally, a C 1-6 alkoxy group (e.g., methoxy) substituted 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group (e.g., azetidinylcarbonyl) and (q) a 3- to 8-membered monocyclic non-aromatic heterocyclylideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino)]], (2) a pyridine ring (optionally oxidized) [optionally condensed with a 5- or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), 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) a C 1-6 alkyl group (e.g., methyl, ethyl) (i) a halogen atom (e.g., a fluorine atom) and (ii) a hydroxy group (d) a C 1-6 alkoxy group (e.g., methoxy, ethoxy) (i) a halogen atom (e.g., a fluorine atom), (ii) a C 1-6 alkoxy group (e.g., methoxy) and (iii) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., oxetanyl) (e) a C 3-10 cycloalkyl group (e.g., cyclopropyl), (f) a C 1-6 alkyl-carbonyl group (e.g., acetyl), (g) a mono- or di-C 1-6 alkylamino group (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino) optionally substituted with 1 to 3 halogen atoms (e.g., a fluorine atom), (h) a mono- or di-C 1-6 alkoxy-carbonylamino group (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 [[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) a C 1-6 alkoxy group (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 Alkylamino group (e.g., N,N-dimethylamino), (4) A pyridazine ring that is further substituted with one cyano group, (5) Pyrazine ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 3 substituents selected from (a) to (b). (a) C 1-6 Alkyl groups (e.g., methyl) and (b) C 1-6 [alkoxy group (e.g., methoxy)] (6) Dihydropyridine ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) or (7) Dihydropyrimidine ring Furthermore, it is substituted with one cyano group, and In some cases, it is further substituted with one or two oxo groups. That is the case.

[0097] In other embodiments, ring A 2 Even more (1) Benzene ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (c). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl group (e.g., methyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (c) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 [alkoxy group (e.g., methoxy)] (2) pyridine ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) C which may be 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 [Furthermore, it is substituted with one cyano group, and Depending on the case, an additional 1 to 4 C 1-6 [Substituted with an alkoxy group (e.g., methoxy)] or (4) Dihydropyridine ring [Furthermore, it is substituted with one cyano group, and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (b). (a) Oxo group and (b) C 1-6 Alkyl groups (e.g., methyl) That is the case.

[0098] In other embodiments, ring A 2 It is more preferable to use the following formula: [ka] This is a substructure represented by ring A, where ring A 3 The cyano group is, in some cases, a further substituted benzene ring, in some cases a further substituted six-membered nitrogen-containing aromatic heteroring, or in some cases a further substituted six-membered nitrogen-containing non-aromatic heteroring. [ka] The substructure represented by this bonds to a carbon atom adjacent to the carbon atom to which it is bonded.

[0099] The "six-membered nitrogen-containing aromatic heteroring" in "a six-membered nitrogen-containing aromatic heteroring which may be further substituted" is preferably a pyridine ring (which may be oxidized), a pyrimidine ring, a pyridazine ring, or a pyrazine ring, and particularly preferably a pyridine ring. The "six-membered nitrogen-containing non-aromatic heteroring that may be further substituted" is preferably a dihydropyridine ring or a dihydropyrimidine ring.

[0100] The "benzene ring" in "a benzene ring that may be further substituted," the "6-membered nitrogen-containing aromatic heteroring" in "a 6-membered nitrogen-containing aromatic heteroring that may be further substituted," and the "6-membered nitrogen-containing non-aromatic heteroring" in "a 6-membered nitrogen-containing non-aromatic heteroring that may be further substituted" are cyano groups and formula: [ka] In addition to the substructure represented by, it may have 1 to 3 further substitutional positions.

[0101] Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds two, each substituent may be the same or different. Furthermore, substituent group A may be substituted with substituents selected from substituent group A. The number of substituents is, for example, 1 to 3. When the number of substituents exceeds two, each substituent may be the same or different.

[0102] Ring A 3 Preferably (1) A benzene ring which is optionally further substituted with 1 to 5 substituents selected from (a) to (q) (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (ii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (k) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (i). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) A six-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) which may be further substituted with one to four substituents selected from (a) to (b) in some cases. (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) That is the case.

[0103] In other embodiments, ring A 3 Preferably (1) A benzene ring which is optionally further substituted with 1 to 5 substituents selected from (a) to (q) (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl (e.g., methyl, ethyl) field, (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) optionally substituted with 1 to 3 substituents selected from (I) to (II) C 1-6 an alkoxy group (e.g., methoxy, ethoxy) (I) C 1-6 alkoxy-C 1-6 an alkoxy group (e.g., methoxyethoxy) and (II) mono- or di-C 1-6 an alkylamino group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 an alkyl-carbonylamino group (e.g., N-acetylamino), (vii) N-C 1-6 alkyl-N-C 1-6 an alkyl-carbonylamino group (e.g., N-methyl-N-acetylamino), (viii) C 3-10 a cycloalkyl group (e.g., cyclobutyl) and (ix) optionally substituted with 1 to 3 substituents selected from (I) to (II) a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) (I) an oxo group and (II) C 1-6 an alkyl group (e.g., methyl) (h) C 1-6 an alkyl-carbonyl group (e.g., acetyl), (i) C 1-6 an alkoxy-carbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl), (j) optionally substituted with 1 to 3 C 1-6 an alkoxy group (e.g., methoxy) a mono- or di-C 1-6 an alkylamino group (e.g., N-ethylamino), (k) optionally substituted with 1 to 3 C 1-6 an alkoxy group (e.g., methoxy) a mono- or di-C 1-6 an alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (i). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) A six-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) which may be further substituted with one to four substituents selected from (a) to (b) in some cases. (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) That is the case.

[0104] In other embodiments, ring A 3 Preferably (1) A benzene ring which may be further substituted with 1 to 5 substituents selected from (a) to (c) in some cases. (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl group (e.g., methyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (c) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy), (2) A six-membered aromatic heterocycle (e.g., pyridine, pyrimidine) which may be further substituted with one to four substituents selected from (a) to (b) in some cases. (a) C which may be 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 six-membered non-aromatic heterocycle (e.g., dihydropyridine) which may be further substituted with one to four substituents selected from (a) to (b) in some cases. (a) Oxo group and (b) C 1-6 Alkyl group (e.g., methyl) That is the case.

[0105] Ring A 3 is more (1) A benzene ring which is optionally further substituted with 1 to 5 substituents selected from (a) to (q) (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (ii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (k) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Pyridine ring (which may be oxidized) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (i). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring which may be further substituted with 1 to 3 substituents selected from (a) to (c) in some cases. (a) amino group, (b) C 1-6 Alkoxy groups (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 Alkylamino group (e.g., N,N-dimethylamino), (4) Pyridazine ring, (5) A pyrazine ring which may be further substituted with 1 to 3 substituents selected from (a) to (b) in some cases. (a) C 1-6 Alkyl groups (e.g., methyl) and (b) C 1-6 Alkoxy groups (e.g., methoxy), (6) A dihydropyridine ring which may be further substituted with 1 to 4 substituents selected from (a) to (b) as applicable. (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) or (7) A dihydropyrimidine ring which may be further substituted with one or two oxo groups.

[0106] In other embodiments, ring A 3 is more (1) A benzene ring which is optionally further substituted with 1 to 5 substituents selected from (a) to (q) (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl (e.g., methyl, ethyl) field, (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case.1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy)1-6 Alkylamino group (e.g., N-ethylamino), (k) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Pyridine ring (which may be oxidized) [In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (i). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (3) A pyrimidine ring which may be further substituted with 1 to 3 substituents selected from (a) to (c) in some cases. (a) amino group, (b) C 1-6 Alkoxy groups (e.g., methoxy, ethoxy) and (c) Mono- or di-C 1-6 Alkylamino group (e.g., N,N-dimethylamino), (4) Pyridazine ring, (5) A pyrazine ring which may be further substituted with 1 to 3 substituents selected from (a) to (b) in some cases. (a) C 1-6 Alkyl groups (e.g., methyl) and (b) C 1-6 Alkoxy groups (e.g., methoxy), (6) A dihydropyridine ring which may be further substituted with 1 to 4 substituents selected from (a) to (b) as applicable. (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) or (7) A dihydropyrimidine ring which may be further substituted with one or two oxo groups. That is the case.

[0107] In other embodiments, ring A 3 is more (1) A benzene ring which may be further substituted with 1 to 5 substituents selected from (a) to (c) in some cases. (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl group (e.g., methyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (c) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy), (2) A pyridine ring which may be further substituted with 1 to 4 substituents selected from (a) to (b) in some cases. (a) C which may be 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) Depending on the case, 1 to 4 additional C 1-6 A pyrimidine ring substituted with an alkoxy group (e.g., methoxy) or (4) A dihydropyridine ring which may be further substituted with 1 to 4 substituents selected from (a) to (b) as applicable. (a) Oxo group and (b) C 1-6 Alkyl group (e.g., methyl) That is the case.

[0108] formula [ka] The substructure represented by formula (A 3 -1)~(A 3 -9); [ka] [During the ceremony, Q 1 is N or CR Q1 And here, R Q1 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atom, (d) Hydroxyl group, (e) Carboxylic group, (f) amino group, (g) C which is substituted in some cases 1-6 alkyl group, (h) C which is replaced in some cases 1-6 Alkoxy group, (I C 1-6 Alkyl-carbonyl group, (j) C 1-6 Alkoxy-carbonyl group, (k) Mono- or di-C as may be substituted. 1-6 Alkylamino group, (l) Mono- or di-C as may be substituted. 1-6Alkyl-carbonylamino group, (m) Mono- or di-C 1-6 Alkoxy-carbonylamino group, (n) mono- or di-C 1-6 Alkyl-carbamoyl group, (o) G-C 1-6 Alkyl sulfinylidene amino group, (p) C 3-10 Cycloalkyl groups, (q) C which is replaced in some cases 3-10 Cycloalkyloxy group, (r) 3-8 member monocyclic non-aromatic heterocyclic group, (s) A 3- to 8-membered monocyclic non-aromatic heterocyclyloxy that may be substituted in some cases. (t) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group which may be substituted in some cases. (u) 3-8 membered monocyclic non-aromatic heterocyclidene amino group And, Q 2 is N or CR Q2 And here, R Q2 teeth (a) Hydrogen atom, (b) Halogen atom or (c) C 1-6 Alkoxy group And, Q 3 is N or CR Q3 And here, R Q3 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atom, (d) Carboxylic group, (e) C which is replaced in some cases 1-6 alkyl group, (f) C which is replaced in some cases 1-6 Alkoxy group, (g) C 1-6 Alkyl-carbonyl group, (h) C 1-6 Alkoxy-carbonyl group, (i) Mono- or di-C 1-6 Alkylamino group, (j) Mono- or di-C as may be substituted. 1-6 Alkyl-carbamoyl group, (k) G-C 1-6 Alkyl sulfinylidene amino group or (l) 3-8 membered monocyclic non-aromatic heterocyclidene amino group And, Q 4 is N or CR Q4 And here, R Q4 teeth (a) A hydrogen atom or (b) Halogen atom And Q 1 Q 2 Q 3 and Q 4 The N atoms are oxidized in each case; R N1 is a hydrogen atom or C 1-6 It is an alkyl group; R N2 is a hydrogen atom or C 1-6 It is an alkyl group; R N3 is a hydrogen atom or C 1-6 It is an alkyl group; and R N4 C is substituted with hydrogen atoms or, in some cases, 1 to 3 halogen atoms. 1-6 It is an alkyl group. This is a substructure represented by [this].

[0109] formula [ka] The substructure represented by is more preferably given by formula (A 3 -1), (A 3 -2), (A 3 -3), (A 3 -5), (A 3 -6) or (A 3 -9); [ka] [In the formula, each symbol is defined as above.] This is a substructure represented by [this].

[0110] Formula (A 3 -1) In, Q 1 Preferably N or CR Q1 And here, R Q1 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (d) Hydroxyl group, (e) Carboxylic group, (f) amino group, (g) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (h) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 substituted with 1-3 substituents selected from (I) to (II) as applicable (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl, oxetanyl) (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (I C 1-6 Alkyl-carbonyl group (e.g., acetyl), (j) C 1-6 Alkoxycarbonyl group (e.g., methoxycarbonyl), (k) Mono- or di-C12 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (l) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (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 group (e.g., N,N-dimethylcarbamoyl), (o) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (p) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (q) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (r) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (s) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (t) Depending on the case, 1 to 3 C 1-6 A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl) substituted with an alkoxy group (e.g., methoxy) or (u) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) That is the case.

[0111] Other embodiments, formula (A 3 -1) In, Q 1 Preferably N or CR Q1 And here, R Q1 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (d) Hydroxyl group, (e) Carboxylic group, (f) amino group, (g) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms)1-6 Alkyl (e.g., methyl, ethyl) field, (h) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 substituted with 1-3 substituents selected from (I) to (II) as applicable (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl, oxetanyl) (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (I C 1-6 Alkyl-carbonyl group (e.g., acetyl), (j) C 1-6Alkoxycarbonyl group (e.g., methoxycarbonyl), (k) Mono- or di-C12 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino, N-ethylamino, N-ethyl-N-methylamino) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (l) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (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 group (e.g., N,N-dimethylcarbamoyl), (o) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (p) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (q) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (r) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (s) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (t) Depending on the case, 1 to 3 C 1-6A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl) substituted with an alkoxy group (e.g., methoxy) or (u) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) That is the case.

[0112] Other embodiments, formula (A 3 -1) In, Q 1 Preferably CR Q1 And here, R Q1 teeth (a) Hydrogen atom, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl group (e.g., methyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 alkoxy group (e.g., methoxy) or (d) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 These are alkoxy groups (e.g., methoxy, ethoxy).

[0113] Formula (A 3 -1) In, Q 2 Preferably, N (which may be oxidized) or CR Q2 And here, R Q2 teeth (a) Hydrogen atom, (b) Halogen atoms (e.g., fluorine atoms) or (c) C 1-6 It is an alkoxy group (for example, methoxy).

[0114] Other embodiments, formula (A 3 -1) In, Q 2 Preferably CRQ2 And here, R Q2 teeth (a) A hydrogen atom or (b) A halogen atom (for example, a fluorine atom).

[0115] Formula (A 3 -1) In, Q 3 Preferably, N (which may be oxidized) or CR Q3 And here, R Q3 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (d) Carboxylic group, (e) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (f) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy), (g) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (h) C 1-6 Alkoxycarbonyl group (e.g., ethoxycarbonyl), (i) Mono- or di-C 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino), (j) No- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino) or (l) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) That is the case.

[0116] Other embodiments, formula (A 3 -1) In, Q 3 Preferably, N (which may be oxidized) or CR Q3 And here, R Q3 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (d) Carboxylic group, (e) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (f) C 1-6 Alkoxy groups (e.g., methoxy), (g) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (h) C 1-6 Alkoxycarbonyl group (e.g., ethoxycarbonyl), (i) Mono- or di-C 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino), (j) No- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino) or (l) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) That is the case.

[0117] Other embodiments, formula (A 3 -1) In, Q 3 Preferably CR Q3 And here, R Q3 teeth (a) Hydrogen atom, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) or (d) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy) That is the case.

[0118] Formula (A 3 -1) In, Q 4 Preferably, N (which may be oxidized) or CR Q4 And here, R Q4 teeth (a) A hydrogen atom or (b) Halogen atoms (e.g., fluorine atoms) That is the case.

[0119] Other embodiments, formula (A 3 -1) In, Q 4 Preferably, N (which may be oxidized) or CH That is the case.

[0120] Other embodiments, formula (A 3 -1) In, Q 4 Preferably N or CR Q4 And here, R Q4 teeth (a) A hydrogen atom or (b) Halogen atoms (e.g., fluorine atoms) That is the case.

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

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

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

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

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

[0126] Ring B 1 It is an aromatic heterocycle that may be further substituted in some cases. The "aromatic heterocycle" in "aromatic heterocycle that may be further substituted in some cases" is a -VZ- ring B 1 In addition, it may have an additional 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds 2, each substituent may be the same or different. The "aromatic heteroring" in "aromatic heteroring that may be further substituted" is preferably a 5-membered aromatic heteroring.

[0127] Ring B 1 Preferably ring B 2 In other words, it is a five-membered aromatic heteroring that may be further substituted in some cases. The "five-membered aromatic heteroring" in "a five-membered aromatic heteroring that may be further substituted in some cases" is -O-CH(R 1 )-CH2-Ring B 2 In addition, it may have an additional 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds 2, each substituent may be the same or different. The "five-membered aromatic heteroring" in "further substituted five-membered aromatic heteroring" is preferably a five-membered nitrogen-containing aromatic heteroring. Examples of five-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, and 1,3,4-thiadiazole.

[0128] Ring B 2 teeth Preferably, a 5-membered nitrogen-containing aromatic heteroring which is further substituted in some cases. More preferably, tetrazole or triazole, each of which may be further substituted. More preferably, tetrazole or triazole, More preferably, it is a tetrazole or triazole, each bonded by its nitrogen. More preferably, it is a tetrazole or 1,2,4-triazole, each of which is bonded at its nitrogen, Particularly preferred is tetrazole-1-yl or 1,2,4-triazol-1-yl.

[0129] V is O, S, S(O), S(O)2 or N(R V ) and here, R V C is a hydrogen atom or, if applicable, substituted. 1-6 It is an alkyl group. "C which is replaced in some cases" 1-6 C 1-6 The alkyl group may have an additional 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds two, each substituent may be the same or different. V is preferably O.

[0130] Z is sometimes substituted for C. 1-6 It is an alkylene group. "C which is replaced in some cases" 1-6 "C" of the alkylene group 1-6 The alkylene group may have an additional 1 to 5 (preferably 1 to 3) substituents at substitutable positions. Examples of substituents include substituents selected from substituent group A above. When the number of substituents exceeds two, each substituent 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 It is preferably methyl. Z is particularly preferably -CH(CH3)-CH2-.

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

[0132] Compound (I) is derived from formulas (I-1) and (I-2): [ka] [In the formula, each symbol is defined as above.] It contains compounds represented by [the formula shown]. Compound (II) is given by formulas (II-1) and (II-2): [ka] [In the formula, each symbol is defined as above.] It contains compounds represented by [the formula shown]. Compound (III) is given by formulas (III-1) and (III-2): [ka] [In the formula, each symbol is defined as above.] It contains compounds represented by [the formula shown].

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

[0134] [Compound A] Compound (II) [wherein, X 1 is N or CR X1 And here, R X1 is a hydrogen atom, a halogen atom (e.g., a fluorine atom) or C 1-6 It is an alkyl group (e.g., methyl); X 2 , X3 and X 4 Each is independently either C or N, and X 2 , X 3 and X 4 One of them is N, and the other two are C; Ring A 2 teeth (1) Benzene ring [In some cases, it is condensed with a 5-6 member monocyclic non-aromatic heterocycle (e.g., dihydrofuran, pyrroline) (i.e., the condensed ring is dihydrobenzofuran, isoindoline), in some cases (a) Oxo group and (b) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl groups (e.g., methyl, ethyl) It is substituted with 1 to 3 substituents selected from, and Depending on the case, it may be further substituted with 1 to 5 substituents selected from (a) to (aa). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) Formyl group, (f) amino group, (g) Carbamoyl group, (h) C which is substituted with 1 to 3 substituents selected from (i) to (v) depending on the case. 1-6 Alkyl alkyl groups (e.g., methyl, ethyl, isopropyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Hydroxyl 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) G-C 1-6 Alkylsulfinylideneamino group (e.g., N-dimethylsulfinylideneamino) (I C 2-6 Alkenyl group (e.g., vinyl), (j) C 2-6 Alkynyl group (e.g., ethynyl), (k) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (l) C 1-6Alkyl-carbonyl group (e.g., acetyl), (m) C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (n) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (o) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino groups (e.g., N-acetylamino, N-propanoylamino), (p) Mono- or di-C12, which may be substituted with 1 to 3 substituents selected from (i) to (ix) as applicable. 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) Hydroxyl 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 group (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 group (e.g., phenyl), (viii) Five-membered or six-membered monocyclic aromatic heterocyclic groups (e.g., pyridyl, imidazolyl, triazolyl) and (ix) A 3- to 8-membered monocyclic non-aromatic heterocyclic group substituted with 1-3 substituents selected from (I) to (III) as applicable (e.g., azetidinyl, morpholinyl, pyrrolidinyl, piperidyl, 1,1-dioxide thiomorpholinyl, tetrahydropyranyl) (I) Hydroxyl group, (II) Oxo group and (III) C 1-6 Alkyl group (e.g., methyl) (q) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (r) C which is substituted with 1 to 3 substituents selected from (i) in some cases. 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy) (i) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl) substituted with alkyl groups (e.g., methyl) (s) C 3-10 Cycloalkylsulfonyl-carbamoyl group (e.g., cyclopropylsulfonylcarbamoyl), (t) C 6-14 Aryl-carbamoyl group (e.g., phenylcarbamoyl), (u) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., morpholinyl, piperazinyl) substituted with alkyl-carbonyl groups (e.g., acetyl), (v) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (w) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl, piperidyl carbonyl, morpholinyl carbonyl) which may be substituted with 1-3 substituents selected from (i) to (v) depending on the case. (i) Hydroxyl 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 groups (e.g., morpholinyl) (x) 9-14 membered bicyclic non-aromatic heterocyclyl carbonyl group (e.g., tetrahydroimidazopyradinylcarbonyltetrahydrotriazolopyradinylcarbonyl), (y) Depending on the case, 1 to 3 C 1-6 A 5-membered or 6-membered monocyclic aromatic heterocyclylcarbamoyl group substituted with an alkyl group (e.g., methyl) (e.g., pyrazolylcarbamoyl, pyridylcarbamoyl), (z) A 3- to 8-membered monocyclic non-aromatic heterocyclylcarbamoyl group substituted with 1-3 substituents selected from (i) to (iv) as applicable (e.g., azetidinylcarbamoyl, piperidylcarbamoyl, pyrrolidinylcarbamoyl) (i) 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) 3-8 member monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Five-membered or six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, thiophene, thiazole, furan) In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and Depending on the case, it may be further substituted with 1 to 4 substituents selected from (a) to (n). (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Carboxy group, (d) amino group, (e) Carbamoyl group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (viii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl, propyl) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Hydroxyl group, (iv) Carboxy group, (v) C 1-6 Alkoxy groups (e.g., methoxy), (vi) C 7-16 Aralkyloxycarbonyl group (e.g., benzyloxycarbonyl), (vii) Mono- or di-C atoms substituted with 1 to 3 substituents selected from (I) to (II), depending on the case. 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 groups (e.g., morpholinyl) (g) C which is substituted with 1 to 3 substituents selected from (i) to (iv) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) C 1-6 Alkoxy groups (e.g., methoxy) and (iv) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (h) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (I C 1-6 Alkyl-carbonyl group (e.g., acetyl), (j) Depending on the case, 1 to 3 C 1-6 C substituted with an alkoxy group (e.g., methoxy) 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl), (k) Mono- or di-C atoms that are substituted in some cases 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 atoms substituted with 1 to 3 substituents selected from (I) to (II) as applicable. 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 group (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) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) A 5-membered or 6-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) which may be further substituted with 1 to 4 substituents selected from (a) to (d) as applicable. (a) Oxo group, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms) and (d) C which may be substituted with 1 to 3 substituents selected from (I) to (III) 1-6 Alkyl groups (e.g., methyl, ethyl) (I) Halogen atoms (e.g., fluorine atoms), (II) Cyano group and (III) C which may be 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 And here, 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 And here, R Y3 is a hydrogen atom or a halogen atom (for example, a fluorine atom); Y 4 is N or CR Y4 And here, R Y4 is a hydrogen atom or a halogen atom (for example, a fluorine atom); Ring B 2 is a 5-membered aromatic heterocycle (preferably tetrazole or triazole (preferably 1,2,4-triazole), each preferably bonded 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 Each is independently either C or N, and X 2 , X 3 and X 4 One of them is N, and the other two are C; Ring A 3 teeth (1) A benzene ring which is optionally further substituted with 1 to 5 substituents selected from (a) to (q) (a) cyano group, (b) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (c) Hydroxyl group, (d) Carboxylic group, (e) amino group, (f) C which is substituted with 1 to 3 substituents selected from (i) to (ii) depending on the case. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (g) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl) which may be substituted with 1-3 substituents selected from (I) to (II) in some cases. (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (h) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (I C 1-6 Alkoxycarbonyl groups (e.g., methoxycarbonyl, ethoxycarbonyl), (j) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkylamino group (e.g., N-ethylamino), (k) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (e.g., N-propanoylamino), (l) Mono- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (n) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (o) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (p) Depending on the case, 1 to 3 C 1-6 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl groups (e.g., azetidinyl carbonyl) substituted with alkoxy groups (e.g., methoxy) and (q) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolane-1-ylideneamino), (2) Six-membered aromatic heterocycles (e.g., pyridine (sometimes oxidized), pyrimidine, pyridazine, pyrazine) In some cases, it condenses with a 5-membered or 6-membered monocyclic aromatic heterocycle (e.g., imidazole) (i.e., the condensed ring is imidazopyridine), and In some cases, it may be further substituted with 1 to 4 substituents selected from (a) to (i). (a) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (b) amino group, (c) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (d) C which is substituted with 1 to 3 substituents selected from (i) to (iii) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) C 1-6 Alkoxy groups (e.g., methoxy) and (iii) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., oxetanyl) (e) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (f) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (g) Mono- or di-C atoms that are substituted in part 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) 3- to 8-membered monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl) or (3) A six-membered non-aromatic heterocycle (e.g., dihydropyridine, dihydropyrimidine) which may be further substituted with one to four substituents selected from (a) to (b) in some cases. (a) Oxo group and (b) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkyl group (e.g., methyl) and; Y 1 is N or CH; Y 2 is N or CR Y2 And here, 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 And here, R Y3 is a hydrogen atom or a halogen atom (for example, a fluorine atom); Y 4 is N or CR Y4 And here, R Y4 is a hydrogen atom or a halogen atom (for example, a fluorine atom); and W is either N or CH.

[0136] [Compound C] [Compound B] [wherein, formula; [ka] The substructure represented by equation (A 3 -1), (A 3 -2), (A 3 -3), (A 3 -5), (A 3 -6) or (A 3 -9); [ka] This is a substructure represented by, Formula (A 3 -1) In, Q 1 is N or CR Q1 And here, R Q1 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (d) Hydroxyl group, (e) Carboxylic group, (f) amino group, (g) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (h) C which is substituted with 1 to 3 substituents selected from (i) to (ix) depending on the case. 1-6 Alkoxy groups (e.g., methoxy, ethoxy, propoxy, isopropoxy, isobutyloxy) (i) Halogen atoms (e.g., fluorine atoms), (ii) Cyano group, (iii) Carboxy group, (iv) Carbamoyl group, (v) C which is substituted with 1 to 3 substituents selected from (I) to (II) depending on the case. 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 group (e.g., N,N-dimethylamino), (vi) mono- or di-C 1-6 Alkyl-carbonylamino group (e.g., N-acetylamino), (vii) NC 1-6 Alkyl-NC 1-6 Alkyl-carbonylamino group (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 substituted with 1-3 substituents selected from (I) to (II) as applicable (e.g., morpholinyl, azetidinyl, pyrrolidinyl, piperidyl, tetrahydropyranyl, oxetanyl) (I) Oxo group and (II) C 1-6 Alkyl group (e.g., methyl) (i) C which is substituted with 1 to 3 substituents selected from (i) to (ii) depending on the case. 1-6 Alkyl-carbonyl group (e.g., acetyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) C 1-6 Alkoxy groups (e.g., methoxy) (j) C 1-6 Alkoxycarbonyl group (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) Depending on the case, 1 to 3 C 1-6 Mono- or di-C molecules substituted with an alkoxy group (e.g., methoxy) 1-6 Alkyl-carbonylamino group (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 group (e.g., N,N-dimethylcarbamoyl), (o) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino), (p) C 3-10 Cycloalkyl groups (e.g., cyclopropyl), (q) Depending on the case, 1 to 3 C 1-6 C substituted with an alkyl group (e.g., methyl) or a 3- to 8-membered monocyclic non-aromatic heterocyclic group (e.g., morpholinyl) 3-10 Cycloalkyloxy group (e.g., cyclohexyloxy), (r) 3-8 member monocyclic non-aromatic heterocyclic groups (e.g., azetidinyl, pyrrolidinyl), (s) A 3-8 member monocyclic non-aromatic heterocyclyloxy group (e.g., pyrrolidinyloxy) which may be substituted with 1-3 oxo groups. (t) Depending on the case, 1 to 3 C 1-6 A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group (e.g., azetidinyl carbonyl) substituted with an alkoxy group (e.g., methoxy) or (u) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) and; Q 2 is N (which may be oxidized) or CR Q2 And here, R Q2 teeth (a) Hydrogen atom, (b) Halogen atoms (e.g., fluorine atoms) or (c) C 1-6 Alkoxy groups (e.g., methoxy) and; Q 3 is N (which may be oxidized) or CRQ3 And here, R Q3 teeth (a) Hydrogen atom, (b) cyano group, (c) Halogen atoms (e.g., fluorine atoms, chlorine atoms), (d) Carboxylic group, (e) C which is substituted with 1 to 3 substituents selected from (i) to (ii) as applicable. 1-6 Alkyl groups (e.g., methyl, ethyl) (i) Halogen atoms (e.g., fluorine atoms) and (ii) Hydroxyl group (f) C which may be substituted with 1 to 3 halogen atoms (e.g., fluorine atoms) 1-6 Alkoxy groups (e.g., methoxy), (g) C 1-6 Alkyl-carbonyl group (e.g., acetyl), (h) C 1-6 Alkoxycarbonyl group (e.g., ethoxycarbonyl), (i) Mono- or di-C 1-6 Alkylamino groups (e.g., N-methylamino, N,N-dimethylamino), (j) No- or di-C, which may be 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) G-C 1-6 Alkyl sulfinylideneamino group (e.g., N-dimethylsulfinylideneamino) or (l) 3- to 8-membered monocyclic non-aromatic heterocyclideneamino group (e.g., 1-oxide-thiolan-1-ylideneamino) and Q 4 is N (which may be oxidized) or CR Q4 And here, 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 It is an alkyl group (for example, 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 It is an alkyl group (for example, methyl), Q 3 is CH, and Q 4 is N or CH; Formula (A 3 -5) In, R N4 It 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 It is an alkyl group (for example, methyl), Q 1 is CH, and Q 4 is CH; and Formula (A 3 -9) R N4 C is substituted with hydrogen atoms or, in some cases, 1 to 3 halogen atoms (e.g., fluorine atoms). 1-6 It is an alkyl group (for example, methyl), Q 2 is CH, and Q 3 It is CH.

[0137] [Compound D] 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-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-tetrazole-1-yl)propane-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-tetrazole-1-yl)propane-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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridine-3-yl]pyridine-3-carbonitrile or a pharmaceutically acceptable salt (Example 284); 4-Fluoro-2-[6-(5-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-3-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 288); 4-Methoxy-2-[6-(3-{[(2S)-1-(1H-tetrazole-1-yl)propane-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-tetrazole-1-yl)propane-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-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)-3H-imidazo[4,5-b]pyridine-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 345); 4-Fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyrazine-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-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)-3H-imidazo[4,5-b]pyridine-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 393); and 4-Fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazole-1-yl)propan-2-yl]oxy}pyridine-2-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile or a pharmaceutically acceptable salt (Example 410).

[0138] Specific examples of compound (I) include the compounds in Examples 1 to 486.

[0139] When compound (I) is a salt, examples of salts 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, and p-toluenesulfonic acid. Examples of preferred salts with basic amino acids include salts with arginine, lysine, and ornithine. Examples of preferred salts with acidic amino acids include salts with aspartic acid and glutamic acid. 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 salts, potassium salts, etc.), alkaline earth metal salts (e.g., calcium salts, magnesium salts, etc.), and ammonium salts. 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, and p-toluenesulfonic acid. When compound (I) contains isomers such as tautomers, optical isomers, stereoisomers, positional isomers, and rotational isomers, any isomer or mixture is also included in the compound of the present invention. Furthermore, when compound (I) contains optical isomers, optical isomers separated from the racemate are included in compound (I). Compound (I) can be obtained in crystalline form. Both single crystal and crystalline mixture forms can be included in compound (I). Compound (I) may be a pharmaceutically acceptable cocrystal or cocrystalline salt. As used herein, a cocrystal or cocrystalline salt refers to a crystalline substance consisting of two or more unique solids at room temperature, each possessing distinctive physical characteristics such as structure, melting point and heat of fusion, hygroscopicity, solubility, and stability. Cocrystals or cocrystalline salts can themselves be produced by known cocrystallization methods. Compound (I) may be a solvate (e.g., a hydrate) or a non-solvate, and both are included in compound (I). Isotopes (for example, 2 H, 3 H, 11 C, 14 C, 18 F, 35 S, 125 Compounds labeled or substituted with isotopes (such as I) are also included in compound (I). Compounds labeled or substituted with isotopes can be used, for example, as tracers in positron emission tomography (PET) (PET tracers), and are expected to be useful in fields such as medical diagnosis.

[0140] The method for producing the compound of the present invention is described below.

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

[0142] When the compounds obtained in each step are in their free form, they can be converted to the desired salt by methods known to the extent of the process. When the compounds obtained in each step are salts, they can be converted to the desired free form or other salts by methods known to the extent of the process.

[0143] The compounds obtained in each step can be used directly or as crude products in subsequent reactions as a reaction mixture. Alternatively, the compounds obtained in each step can be isolated or purified from the reaction mixture by known methods, such as concentration, crystallization, recrystallization, distillation, solvent extraction, fractional distillation, column chromatography, and other separation methods.

[0144] When the raw materials and reagents used in each process are commercially available, commercially available products may also be used directly.

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

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

[0147] The pressure in each reaction step varies depending on the type of reagents and solvents used, but unless otherwise specified, it is generally between 1 atmosphere and 20 atmospheres, preferably between 1 atmosphere and 3 atmospheres.

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

[0149] In each step of the reaction, reagents are used in amounts of 0.5 to 20 equivalents, preferably 0.8 to 5 equivalents, relative to the substrate, unless otherwise specified. When using a reagent as a catalyst, the reagent is used in amounts of 0, or 0.001 to 1 equivalent, preferably 0.01 to 0.2 equivalents, relative to the substrate. When using a reagent as a ligand, the reagent is used in amounts of 0.001 to 1 equivalent, preferably 0.01 to 0.2 equivalents, relative to the substrate. When using a reagent as a reaction solvent, the reagent is used in solvent amounts.

[0150] Unless otherwise specified, the reactions in each step are carried out without solvent or by dissolving or suspending the raw material compounds in a suitable solvent. Examples of solvents 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. Anhydrous substances: such as acetic anhydride; Organic acids: formic acid, acetic acid, trifluoroacetic acid, etc. Inorganic acids: hydrochloric acid, sulfuric acid, etc. Esters: such as ethyl acetate; Ketones: such as acetone and methyl ethyl ketone; water. The above solvents can be used as a mixture of two or more solvents in appropriate ratios.

[0151] When bases are used in the reactions of each step, examples 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: such as sodium hydride; 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 will be carried out using methods known in themselves, for example, by methods described in the following books or examples: Experimental Chemistry Course, 5th Edition, Vols. 13-19 (edited by the Chemical Society of Japan); New Experimental Chemistry Course, Vols. 14-15 (edited by the Chemical Society of Japan); Precision Organic Synthesis, Revised 2nd Edition (LF Tietze, Th. Eicher, Nankodo); Revised Named Organic Reactions: Their Mechanisms and Key Points (Hideo Togo, Kodansha); ORGANIC SYNTHESES Collective Volume 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, Vol.1-Vol.14 (Elsevier Japan); Organic Synthesis Strategies Learned from Named Reactions (translated by Kiyoshi Tomioka, Kagaku Dojin); Comprehensive Organic Transformations (VCH Publishers Inc.), 1989, etc.

[0154] In each step, the functional group protection or deprotection reaction is carried out by a method known in itself, for example, by the methods 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 by the methods described in the examples. Examples of protecting groups for hydroxyl groups and phenolic hydroxyl groups of alcohols include ether-type protecting groups, such as methoxymethyl ether, benzyl ether, tert-butyldimethylsilyl ether, and tetrahydropyranyl ether; carboxylate-type protecting groups, such as acetate; sulfonic acid-type protecting groups, such as methanesulfonic acid; and carbonate-type protecting groups, such as tert-butyl carbonate. Examples of protecting groups for the carbonyl group of aldehydes include acetal-type protecting groups, such as dimethylacetal; and cyclic acetal-type protecting groups, such as 1,3-dioxane. Examples of protecting groups for the carbonyl group of ketones 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 carboxyl protecting groups include ester-type protecting groups, such as methyl esters; and amide-type protecting groups, such as N,N-dimethylamide. Examples of thiol protecting groups include ether-type protecting groups, such as benzyl thioether; and ester-type protecting groups, such as thioacetic acid esters, thiocarbonates, and thiocarbamates. Protecting groups for amino groups and aromatic heterocycles, such as imidazole, pyrrole, and indole, include carbamate protecting groups, such as benzylcarbamate; amide protecting groups, such as acetamide; alkylamine protecting groups, such as N-triphenylmethylamine; and sulfonamide protecting groups, such as methanesulfonamide. Protecting groups can be removed by methods known in themselves, such as using acids, bases, ultraviolet light, hydrazine, phenylhydrazine, sodium N-methyldithiocarbamate, tetrabutylammonium fluoride, palladium acetate, trialkylsilyl halides (e.g., trimethylsilyl iodide, trimethylsilyl bromide), or by reduction methods.

[0155] When reduction reactions are carried out in each step, examples of reducing agents 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 boranetetrahydrofuran complexes; Raney nickel; Raney cobalt; hydrogen; formic acid; triethylsilane, etc. When reducing carbon-carbon double or triple bonds or nitro groups or benzyloxycarbonyl groups, catalysts, such as palladium-carbon or Lindler catalysts, may be used.

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

[0157] When radical reactions are carried out in each step, examples of radical initiators 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; and benzoyl peroxides. Examples of radical reagents used include tributylstannane, tristrimethylsilylsilane, 1,1,2,2-tetraphenyldisilane, diphenylsilane, and samarium iodide.

[0158] When nucleophilic substitution reactions are carried out in each step, examples of bases used include organolithium (e.g., lithium bis(trimethylsilyl)amide), metal alkoxides (e.g., potassium tert-butoxide), alkali metal hydrides (e.g., sodium hydride), inorganic bases, and organic bases.

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

[0160] When a nucleophilic addition reaction using a carbanion, a nucleophilic 1,4-addition reaction using a carbanion (Michael addition reaction), or a nucleophilic substitution reaction using a carbanion is carried out in each step, examples of bases used for carbanion production include organolithium, metal alkoxides, inorganic bases, and organic bases.

[0161] When carrying out a Grignard reaction in each step, examples of Grignard reagents used include aryl magnesium halides, such as phenylmagnesium bromide; and alkylmagnesium halides, such as methylmagnesium bromide. Grignard reagents can be prepared by methods known to themselves, for example, by reacting an alkyl halide or aryl halide with metallic magnesium in ether or tetrahydrofuran as a solvent.

[0162] When carrying out azination reactions of alcohols, alkyl halides, or sulfonates in each step, examples of azinating agents used include diphenylphosphoryl azide (DPPA), trimethylsilyl azide, and sodium azide. For example, for the azination reaction of alcohols, methods using diphenylphosphoryl azide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and methods using trimethylsilyl azide and Lewis acid are used.

[0163] When reductive amination reactions are carried out in each step, examples of reducing agents used include sodium triacetoxybolohydride, sodium cyanobolohydride, borane-2-methylpyridine complex, hydrogen, and formic acid. When the substrate is an amine compound, examples of carbonyl compounds used include paraformaldehyde, aldehydes such as acetaldehyde, and ketones such as cyclohexanone. When the substrate is a carbonyl compound, examples of amines 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 azodicarboxylate (e.g., diethylazodicarboxylate (DEAD), diisopropylazodicarboxylate (DIAD), etc.) and triphenylphosphine, or a phosphone reagent (e.g., cyanomethylenetributylphosphone (Kakuda Reagent)) is used as the reagent.

[0165] When carrying out esterification, amidation, or urea formation reactions in each step, the reagents used include acyl halides, such as acid chlorides and acid bromides; and activated carboxylic acids, such as anhydrides, activated esters, and sulfates. Examples of carboxylic acid activators include carbodiimide condensing agents, e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCD); triazine condensing agents, e.g., 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methylmorpholinium chloride n-hydrate (DMT-MM); carbonate condensing agents, e.g., 1,1-carbonyldiimidazole (CDI); diphenylphosphoryl azide (DPPA); benzotriazole-1-yloxytrisdimethylaminophosphonium salt (BOP reagent); 2-chloro-1-methylpyridinium iodide (Mukoyama reagent); thionyl chloride; lower alkyl haloformates, e.g., ethyl chloroformate; O-(7-azabenzotriazole-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphorate (HATU); sulfuric acid; and combinations thereof. When using carbodiimide coupling agents, additives such as 1-hydroxybenzotriazole (HOBt), N-hydroxysuccinimide (HOSu), and dimethylaminopyridine (DMAP) may be added to the reaction system.

[0166] Examples of metal catalysts used when carrying out coupling reactions in each step include palladium compounds, such as palladium(II) acetate, tetrakis(triphenylphosphine)palladium(O), dichlorobis(triphenylphosphine)palladium(II), tris(dibenzylideneacetone)dipalladium(O), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II), (tri-tert-butylphosphine)palladium(O), etc.; nickel compounds, such as tetrakis(triphenylphosphine)nickel(O), etc.; rhodium compounds, such as tris(triphenylphosphine)rhodium(III) chloride, etc.; cobalt compounds; copper compounds, such as copper oxide, copper(I) iodide, copper(II) diacetate, etc.; platinum compounds, etc. Furthermore, bases 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, ligands may be added to the reaction system, examples of which include organic amines, such as N,N'-dimethylethylenediamine, N,N'-dimethylcyclohexane-1,2-diamine, 2,2-bipyridyl, etc.; organophosphorus 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 thiocarbonylation reactions are carried out in each step, phosphorus pentasulfide is typically used as the thiocarbonylating agent. Alternatively, reagents 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 phosphorus pentasulfide.

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

[0169] When carrying out a sulfonic acid esterification reaction in each step, examples of sulfonating agents used include methanesulfonyl chloride, p-toluenesulfonyl chloride, methanesulfone anhydride, and p-toluenesulfone anhydride.

[0170] When hydrolysis reactions are carried out in each step, acids or bases are used as reagents. For the acid hydrolysis reaction of tert-butyl esters, formic acid, triethylsilane, etc., can be added to the by-product, reductively trapped tert-butyl cation.

[0171] When carrying out the dehydration reaction in each step, examples of dehydrating agents used include sulfuric acid, phosphorus pentoxide, phosphorus oxychloride, N,N'-dicyclohexylcarbodiimide, alumina, and polyphosphate.

[0172] Examples of metal catalysts used when carrying out the cyanation reaction in each step include palladium compounds, such as chloro(2-dicyclohexylphosphin-2',4',6'-tri-i-propyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II), palladium(II) acetate, tetrakis(triphenylphosphine)palladium(O), dichlorobis(triphenylphosphine)palladium(II), and tris(dibenzylideneacetone). Examples of cyano compounds used include dipalladium(O), 1,1'-bis(diphenylphosphin)ferrocenepalladium(II) chloride, (tri-tert-butylphosphine)palladium(O), etc.; nickel compounds, e.g., tetrakis(triphenylphosphine)nickel(O), etc.; rhodium compounds, e.g., tris(triphenylphosphine)rhodium(III) chloride, etc.; cobalt compounds; copper compounds, e.g., copper oxide, copper(I) iodide, copper(II) diacetate, etc.; platinum compounds, etc. Examples of cyano compounds used include potassium hexacyanoferrate(II) trihydrate, copper(I) cyanide, zinc cyanide, potassium cyanide, sodium cyanide, etc. Furthermore, bases may be added to the reaction system, examples of which include organic bases, inorganic bases, etc. Furthermore, ligands may be added to the reaction system, examples of which include organic amines such as N,N'-dimethylethylenediamine, N,N'-dimethylcyclohexane-1,2-diamine, and 2,2-bipyridyl; and organophosphorus compounds such as 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, triphenylphosphine, tri-tert-butylphosphine, tricyclohexylphosphine, and BINAP(2,2'-bis(diphenylphosphino)-1,1-binaphthyl).

[0173] When carrying out the nitration reaction in each step, examples of nitrating agents used include mineral acids, such as acid mixtures and nitric acid; and nitric acid, such as potassium nitrate, sodium nitrate, tetramethylammonium nitrate, and silver nitrate.

[0174] When O-alkylation or N-alkylation reactions are carried out in each step, a combination of alkylating agent (e.g., alkyl halide, alkyl sulfonic acid ester, etc.) and 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 produced 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 defined above.

[0176] X 2 C is X 3 and X 4 Compound (I), in which one element 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] Here, L 1 ~L 4 Each of these is an independent leaving group, M 1 and M 2 Each of these is an independent metal group, T 1 is a leaving group or a metallic group, and the other symbols are as defined above.

[0177] L 1 ~L 4 and T 1 Examples of "leaving groups" include halogen atoms (e.g., fluorine, chlorine, bromine, iodine, etc.), and sometimes halogenated C 1-6 Alkyl sulfonyloxy groups (e.g., methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy, etc.), and in some cases substituted C 6-14 Aryl sulfonyl oxy group [for example, C depending on the case] 1-6A C having 1 to 3 substituents selected from alkyl groups (e.g., methyl). 6-14 [Aryl sulfonyl oxy group], possibly halogenated C 1-6 Alkyl sulfide group, optionally substituted C 6-14 Aryl sulfide group, C 1-6 This includes alkoxy groups (e.g., methoxy), nitro groups, m-nitrobenzenesulfonyloxy and naphthylsulfonyloxy. M 1 M 2 and T 1 Examples of "metal groups" include boronic acid groups (-B(OH)2) or boronic acid ester groups (-B(OR)2; R is C 1-6 This includes alkyl groups or their cyclic groups (e.g., 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) or trialkylstanyl groups. Compounds (2), (3), (7), and (9) may be commercially available products or can be produced by methods known in themselves.

[0178] X 1 CH is X 2 and X 4 C is X 6 CH is 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] Here, T 2 is a leaving group or a metallic group, and the other symbols are as defined above.

[0179] T 2 An example of a "leaving group" is T 1 This includes those exemplified as "leaving groups". T 2 An example of a "metal group" is T 1 This includes those exemplified as "metal groups". Compounds (3'), (9), and (11) may be commercially available products or can be prepared by methods known in themselves.

[0180] X 1 CR X1a X 3 and X 4 C is X 6 CR X6 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] Here, L 5 is a leaving group, M 3 is a metal group, R X1a is a hydrogen atom or C 1-2 It is an alkyl group, and R is C 1-2 It 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 This includes those exemplified as "leaving groups". M 3 An example of a "metal group" is M 1 and M 2 This includes those exemplified as "metal groups". Compounds (2), (12), (13), and (16) may be commercially available products or can be prepared by methods known in themselves. Compound (5) can be prepared by scheme 1-1.

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

[0183] L 6 Examples of "leaving groups" are L 1 ~L 4 This includes those exemplified as "leaving groups". Compounds (19), (20), (22), and (23) may be commercially available products or can be produced by methods known in themselves.

[0184] The starting compounds and / or intermediates of 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 formed by compound (I) in some cases. When isomerization occurs in the stereoisomers (E and Z forms) of compound (I), the pure compound can be isolated and purified by conventional separation methods, such as extraction, recrystallization, distillation, and chromatography. Furthermore, the corresponding pure isomers can also be obtained by isomerizing the double bond using methods such as heating, acid catalysts, transition metal complexes, metal catalysts, radical catalysts, photoirradiation, and strong base catalysts, as described in or similar to the methods described in New Experimental Chemistry Series 14 (edited by the Chemical Society of Japan), pp. 251-253, and 4th Edition Experimental Chemistry Series 19 (edited by the Chemical Society of Japan), pp. 273-274.

[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 a hydrate or an unhydrated compound. If desired, compound (I) can be synthesized by deprotection, acylation, alkylation, hydrogenation, oxidation, reduction, carbon chain extension, halogenation, substituent exchange, coupling, reductive amination, nucleophilic addition with carbanions, Grignard reagents, and deoxygenative fluorination reactions, either individually or in combination of two or more of these. When the target product is obtained in free form by the above reaction, it can be converted to a salt by conventional methods, or when the target product is obtained as a salt, it can be converted to a 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, and chromatography. When compound (I) contains configurational isomers, diastereomers, conformational isomers, etc., each can be isolated by the separation and purification methods described above, 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) thus obtained, other reaction intermediates, and their starting compounds can be isolated and purified from the reaction mixture by methods known to themselves, such as extraction, concentration, neutralization, filtration, distillation, recrystallization, column chromatography, thin-layer chromatography, preparative high-performance liquid chromatography (preparative HPLC), and medium-pressure preparative liquid chromatography (medium-pressure preparative LC).

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

[0188] Compound (I) may be a prodrug. A prodrug of compound (I) is a compound that is converted to compound (I) by reactions such as enzymes and stomach acid under physiological conditions in the body; that is, a compound that is converted to compound (I) by oxidation, reduction, hydrolysis by enzymes, etc.; or a compound that is converted to compound (I) by hydrolysis by stomach acid, etc.

[0189] The prodrug of compound (I) is a compound obtained by acyling, alkylating, or phosphorylating the amino group of compound (I) (for example, a compound obtained by eicosanoylating, alanylating, pentylaminocarbonylating, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxycarbonylating, tetrahydrofuranylating, pyrrolidylmethylating, pivaloyloxymethylating, or tert-butylating the amino group of compound (I)); or a compound obtained by acyling, alkylating, phosphorylating, or boronating the hydroxyl group of compound (I) (for example, a compound obtained by acetylating, palmitoylating, propanoylating, pivaloylating, or scutellating the hydroxyl group of compound (I)). Compounds obtained by synylation, fumalylation, alanylation, or dimethylaminomethylcarbonylation, etc.; compounds obtained by esterifying or amidating the carboxyl group of compound (I) (for example, compounds obtained by ethyl esterification, phenyl esterification, carboxymethyl esterification, dimethylaminomethyl esterification, pivaloyloxymethyl esterification, ethoxycarbonyloxyethyl esterification, phthalidyl esterification, (5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl esterification, cyclohexyloxycarbonylethyl esterification, or methylamidation, etc.). Any of these compounds can be produced from compound (I) by methods known in themselves. Prodrugs of compound (I) may be compounds that can be converted to compound (I) under the physiological conditions described in Pharmaceutical Development, Vol. 7, Molecular Design, 163-198, Hirokawa Shoten (1990).

[0190] Compound (I) or its prodrug (hereinafter referred to as the Compound of the Invention) exhibits excellent in vivo dynamics (e.g., plasma drug half-life, brain motility, metabolic stability) and low toxicity (e.g., hepatotoxicity, acute toxicity, chronic toxicity, genotoxicity, reproductive toxicity, cardiotoxicity, cytotoxicity, drug interactions, carcinogenicity, etc.; particularly superior as a pharmaceutical in terms of hepatotoxicity). The Compound of the Invention is used directly as a pharmaceutical or mixed with a pharmaceutically acceptable carrier, etc., to be safely administered orally or non-enterally to mammals (e.g., humans, monkeys, cattle, horses, pigs, mice, rats, hamsters, rabbits, cats, dogs, sheep, and goats). Examples of "non-enteral" administration include intravenous, intramuscular, subcutaneous, intra-organ, intranasal, intradermal, ophthalmic, intracerebral, intrarectal, intravaginal, intraperitoneal and intratumoral administration, administration near tumors, etc., and direct administration to lesions.

[0191] The compounds of the present invention have excellent CaMKII inhibitory activity, and therefore, for example, in animals, especially mammals (e.g., humans, monkeys, cats, pigs, horses, cattle, mice, rats, guinea pigs, dogs, rabbits, etc.), Cardiac diseases (including chronic heart failure such as cardiac hypertrophy, acute and congestive heart failure, cardiomyopathy, angina pectoris, myocarditis, atrial / ventricular arrhythmias, tachycardia, and myocardial infarction), myocardial ischemia, venous insufficiency, progression to heart failure after myocardial infarction, hypertension, cor pulmonale, arteriosclerosis including atherosclerosis (aneurysms, coronary artery atherosclerosis, cerebral artery atherosclerosis, peripheral artery atherosclerosis, etc.), post-intervention vascular thickening, vascular thickening / occlusion and organ damage (percutaneous coronary angioplasty, stent placement, coronary angioscopy, intravascular ultrasound, coronary thrombolysis, etc.), post-bypass surgery vascular reocclusion / restenosis, post-cardiopulmonary bypass cardiac dysfunction, respiratory diseases (common cold syndrome, pneumonia, asthma, pulmonary hypertension, pulmonary thromboembolism, etc.), bone Disorders (non-metabolic bone disorders, e.g., fractures, re-fractures, bone malformations / degenerative spondylosis, osteosarcoma, myeloma, dysostosis and scoliosis, bone defects, osteoporosis, osteomalacia, rickets, osteitis-fibrosis, renal osteodystrophy, Paget's disease of bone, myelitis with rigidity, rheumatoid arthritis, osteoarthritis of the knee and similar disorders, etc.), inflammatory diseases (diabetic complications, e.g., retinopathy, nephropathy, nerve damage, macrovascular disorders, etc.; arthritis, e.g., rheumatoid arthritis, osteoarthritis, rheumatoid myelitis, periostitis, etc.; post-surgical / traumatic inflammation; swelling reduction; pharyngitis; cystitis; pneumonia; atopic dermatitis; inflammatory bowel disease, e.g., Crohn's disease, ulcerative colitis, etc.; meningitis; inflammatory eye diseases;Inflammatory lung diseases (e.g., pneumonia, silicosis, pulmonary sarcoidosis, pulmonary tuberculosis), allergic diseases (e.g., allergic rhinitis, conjunctivitis, gastrointestinal allergies, pollen allergies, anaphylaxis), drug addiction, neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, AIDS encephalopathy), central nervous system injuries (e.g., cerebral hemorrhage and cerebral infarction and their sequelae and complications, head injuries, spinal cord injuries, cerebral edema, sensory dysfunction, sensory abnormalities, autonomic dysfunction, abnormal autonomic function, multiple sclerosis), dementia, memory confusion, confusion of consciousness, amnesia, anxiety symptoms, neurological symptoms, unpleasant conditions, mental disorders (depression, epilepsy, arco) Prevention or treatment of conditions such as diabetes mellitus (including diabetes dependence), ischemic peripheral circulatory disorders, deep vein thrombosis, obstructive peripheral circulatory disorders, arteriosclerosis obliterans (ASO), thromboangiitis obliterans, diabetes mellitus (type 1 diabetes, type 2 diabetes, gestational diabetes, etc.), diabetic complications (neuropathy, nephropathy, retinopathy, cataracts, macrovascular complications, osteopenia, diabetic hyperosmolar diabetic coma, infections, diabetic gangrene, dry mouth, hearing impairment, cerebrovascular injury, peripheral circulatory disorders, etc.), urinary incontinence, metabolic / nutritional disorders (obesity, hyperlipidemia, hypercholesterolemia, diabetes mellitus, 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 injury (asymptomatic cerebrovascular injury, transient ischemic attack, stroke, vascular dementia, hypertensive encephalopathy, cerebral infarction, etc.), cerebral edema, cerebral circulatory disorders, recurrence and sequelae of cerebrovascular injury (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, complications of dialysis, organ damage including nephropathy due to irradiation, etc.), post-transplant polycythemia / hypertension / organ damage / vascular thickening, post-transplant rejection, eye disorders (glaucoma, eye Hypertension, thrombosis, multiple organ failure, endothelial dysfunction, hypertensive tinnitus, other circulatory diseases (ischemic cerebral circulatory disorder, Raynaud's disease, Buerger's disease, etc.), chronic obstructive pulmonary disease, interstitial pneumonia, Pneumocystis pneumonia, connective tissue disorders (e.g., systemic lupus erythematosus, scleroderma, polyarteritis, etc.), liver disorders (including chronic hepatitis and cirrhosis, etc.), portal hypertension, digestive disorders (gastritis, gastric ulcer, gastric cancer, post-gastric surgery complications, indigestion, esophageal ulcer, pancreatitis, colon polyps, gallstones, hemorrhoids, ruptured esophageal and gastric varices, etc.), hematological / hematopoietic disorders (polycythemia, vascular purpura, autoimmune hemolysis, etc.), Anemia, disseminated intravascular coagulation, multiple myeloma, etc.), solid tumors, tumors (malignant melanoma, malignant lymphoma, gastrointestinal cancer (e.g., stomach, intestine, 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 disorders (cystitis, benign prostatic hyperplasia, prostate cancer, sexually transmitted diseases, etc.), gynecological disorders (menopausal disorders, pre-eclampsia, endometriosis, uterine fibroids, ovarian diseases, breast diseases, sexually transmitted diseases, etc.), diseases caused by environmental / occupational factors (e.g.) For example, radiation damage, damage from ultraviolet / infrared / laser beams, altitude sickness, etc., infectious diseases (e.g., viral infections such as cytomegalovirus, influenza virus and herpesvirus, rickettsial infections, bacterial infections, etc.), toxemia (sepsis, septic shock, endotoxin shock, Gram-negative sepsis, toxic shock syndrome, etc.), ear, nose, and throat diseases (Meniere's disease, tinnitus, taste disorders, vertigo, balance disorders, dysphagia, etc.), skin diseases (keloids, hemangiomas, psoriasis, etc.), dialysis (hypotension, myasthenia gravis, systemic diseases, e.g., chronic fatigue syndrome, etc.),In particular, prevention or treatment of heart disease (especially catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmias), It is expected to be useful for this purpose. Here, the concept of preventing heart disease includes prognostic treatments such as myocardial infarction, angina attacks, cardiac bypass surgery, thrombolytic therapy, and coronary recanalization, while the concept of treating heart disease includes suppressing the progression or severity of heart failure (including both systolic failure HFrEF and heart failure HFpEF with preserved ejection fraction) and maintaining cardiac function when non-pharmacological treatments (e.g., implantable cardioverter-defibrillators, cardiac sympathectomy, catheter ablation, cardiac pacemakers, intra-aortic balloon pumping, ventricular assist devices, Batista procedure, cell transplantation, gene therapy, heart transplantation, etc.) are performed for severe heart failure / arrhythmia. When the compounds of the present invention are applied to prevent or treat heart failure, it is expected that improvements in cardiac contractility or relaxation will be achieved with short-term administration without side effects such as hypotension, tachycardia, or decreased renal blood flow, regardless of differences in underlying diseases such as ischemic heart disease, cardiomyopathy, and hypertension, and in symptoms such as systolic failure and diastolic failure. Furthermore, in addition to short-term improvement in cardiac function, long-term improvement in prognosis (survival rate, readmission rate, cardiac event rate, etc.) is expected. When the compounds of the present invention are applied to the prevention or treatment of arrhythmias, symptom improvement or remission is expected regardless of the etiology and atrial / ventricular differences. Furthermore, long-term improvement in prognosis (survival rate, readmission rate, cardiac event rate, etc.) is expected.

[0192] The dosage of the compound of the present invention varies depending on the route of administration, symptoms, etc., but for example, when the compound is orally administered to a patient with heart disease (adult, body weight 40-80 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] A pharmaceutical product 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 by a method known in itself (e.g., a method described in the Japanese Pharmacopoeia) as a method for producing a pharmaceutical product. A pharmaceutical product containing the compound of the present invention can be used, for example, as tablets (sugar-coated tablets, film-coated tablets, sublingual tablets, orally disintegrating tablets, buccal tablets, etc.), pills, powders, granules, capsules (including soft capsules and microcapsules), lozenges, syrups, liquids, emulsions, suspensions, controlled-release formulations (e.g., immediate-release formulations, sustained-release formulations, sustained-release microcapsules), aerosols, and films (e.g., orally disintegrating films, oral mucosal adhesive films). It can be safely administered orally or non-enterally (e.g., intravenously, intramuscularly, subcutaneously, intra-organally, intranasally, intradermally, ointmentally, intraperitoneally, intra-abdominally) in the form of films, injections (e.g., subcutaneous, intravenous, intraintramuscular, intramuscular, intramuscular, intra-abdominal and intra-focal) in the form of nasal preparations, transdermal preparations, ointments, lotions, adhesive preparations, suppositories (e.g., rectal suppositories, vaginal suppositories), pellets, nasal preparations, lung preparations (inhalants), eye drops, etc.

[0194] As described above under "Pharmacologically Acceptable Carriers," various organic or inorganic carriers conventionally used as formulation materials (starting materials) may be used. For example, additives, lubricants, binders, and disintegrants are used in solid formulations, while solvents, solubilizers, suspending agents, isotonic agents, buffers, and sedatives are used in liquid formulations. When necessary, formulation additives such as preservatives, antioxidants, colorants, and sweeteners may also be used. Examples of additives include lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, and light anhydrous silicic acid. Examples of lubricants include magnesium stearate, calcium stearate, talc, and colloidal silica. Examples of binders include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, starch, sucrose, gelatin, methylcellulose, and sodium carboxymethylcellulose. Examples of disintegrants include starch, carboxymethylcellulose, carboxymethylcellulose calcium, sodium carboxymethyl starch, and L-hydroxypropylcellulose. Examples of solvents include injectable water, alcohol, propylene glycol, macrogol, sesame oil, corn oil, and olive oil. Examples of solubilizers include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, and sodium citrate. Examples of suspending agents include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glyceryl monostearate; and hydrophilic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose. Examples of isotonic agents include glucose, D-sorbitol, sodium chloride, glycerin, and D-mannitol. Examples of buffering agents include buffer solutions such as phosphoric acid, acetic acid, carbonic acid, and citric acid. Examples of sedatives include benzyl alcohol. Examples of preservatives include p-oxybenzoate, chlorobutanol, benzyl alcohol, phenylethyl alcohol, dehydroacetic acid, and sorbic acid. Examples of antioxidants include sulfites, ascorbic acid, and α-tocopherol.

[0195] The pharmaceutical composition varies depending on the dosage form, administration method, carrier, etc., but it can be manufactured by conventional methods by adding the compound of the 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 compounds of the present invention are applied to each of the above diseases, they can be used in appropriate combination with drugs (hereinafter abbreviated as concomitant drugs) or treatment methods commonly 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 antagonist / NEP inhibitors Combination drugs (Entresto), β-receptor antagonists (e.g., propranolol, nadolol, timolol, nipradilol, bnitrolol, indenolol, penbutrol, carteolol, carvedilol, pindolol, acebutolol, atenolol, bisoprolol, metoprolol, labetalol, amosuralol, arotinolol, etc.), Ca antagonists (e.g., manidipine, nicardipine, nilvadipine, nisoldipine, nitrendipine, benidipine, amlodipine, alanidipine) Diuretics (e.g., thiazide diuretics, such as benzylhydrochlorothiazide, cyclopentiazide, etiazide, hydrochlorothiazide, hydroflumethiazide, meticlothiazide, penfluthiazide, polythiazide, trichloramethiazide, etc.); loop diuretics, such as chlorthalidone, clofenamide, indapamide, mefluside, meticran, sotrazone, tribamide, quinetazon, metrazone, furosemide, mefluside, etc.); potassium-sparing diuretics, such as spironolactone, triamterene, etc. ), digitalis preparations (e.g., digitoxin, digoxin, methyldigoxin, lanatoside C, proscillaridine, etc.), ANP or BNP preparations, Ca sensitizers (e.g., pimobendan, etc.), anticoagulants (e.g., warfarin, sodium citrate, activated protein C, tissue factor pathway inhibitors, antithrombin III, dalteparin sodium, aragatroban, gabexate, ozagrel sodium, ethylicosapentate, beraprost sodium, alprostadil, pentoxifylline, thisokinase,(e.g., streptokinase), antiarrhythmic drugs (e.g., sodium channel blockers, e.g., quinidine, procainamide, disopyramide, ajmaline, cibenzoline, lidocaine, diphenylhydantoin, mexiletine, propafenone, flecainide, pilsicainide, phenytoin, etc.; potassium channel blockers, e.g., amiodarone, etc.; calcium channel blockers, e.g., verapamil, diltiazem, etc.), PDE inhibitors (e.g., amrinone, milrinone, olprinone hydrochloride, etc.), diabetes medications (e.g., sulfonylureas, e.g., tolbutamide, chlorpropamide, glycopyramide, acetohexamide, trazamide, g It can be used simultaneously with drugs such as ribenclamide, glibzol, biguanides (e.g., metformin hydrochloride, buformin hydrochloride), α-glucosidase inhibitors (e.g., voglibose, acarbose), insulin sensitizers (e.g., pioglitazone, troglitazone), SGLT2 inhibitors (e.g., ipragliflozin, dapagliflozin, luseogliflozin, tofogliflozin, canagliflozin, empagliflozin), insulin, glucagon, drugs for treating diabetic complications (e.g., epalrestat), and anti-obesity drugs, and is also possible during implantable artificial hearts, implantable cardioverter-defibrillators, ventricular pacing, Batista procedures, heart transplants, or cell transplants. 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 β-receptor antagonists, as well as non-pharmacological treatments (e.g., implantable cardioverter-defibrillators, cardiac sympathectomy, catheter ablation, cardiac pacemakers, etc.) can be used concurrently. In addition, during the post-acute myocardial infarction or post-myocardial infarction period, for example, the compound can be used concurrently with antithrombotic agents (e.g., anticoagulants, e.g., heparin sodium, heparin calcium, warfarin, etc.; thrombolytic agents, e.g., urokinase, etc.; antiplatelet agents, e.g., aspirin, sulfinpyrazone (Anzlan), dipyridamole (Persantin),It can be used in combination with ticlopidine (Panaldine), cilostazol (Pletal), clopidogrel, etc., angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, β-receptor antagonists, diabetes medications, hyperlipidemia medications (e.g., HMG-CoA reductase inhibitors, e.g., pravastatin, fluvastatin, cerivastatin, atorvastatin, etc.; fibrate drugs, e.g., symfibrate, clinofibrate, fenofibrate, etc.), coronary artery reconstruction surgery, e.g., PTCA, CABG, etc. Furthermore, in rheumatoid arthritis, for example, compounds are used as 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, oxaprozine, flurbiprofen, fenbufen, pranoprofen, phloxaphenin, epirizole, tiaramide hydrochloride, zaltoprofen, gabexate mesylate, camostat mesylate, urinastatin, colchicine, probenecid, sulfinpyrazone, benzbromarone, allopurinol, sodium aurthiomalate, sodium hyaluronate, sodium salicylate, morphine hydrochloride, Salicylic acid, atropine, scopolamine, morphine, pethidine, levorphanol, ketoprofen, naproxen, oxymorphone or their salts, etc.), immunomodulators or immunosuppressants (e.g., methotrexate, cyclosporine, tacrolimus, gusperimus, azathioprine, antilymphocyte serum, dried sulfonated immunoglobulin, erythropoietin, colony-stimulating factor, interleukin, interferon, 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.) and cyclooxygenase inhibitors (e.g., salicylic acid derivatives such as celecoxib, lofecoxib, aspirin, MK-663, valdecoxib, SC-57666, thilacoxib, S-2474, diclofenac, indomethacin, loxoprofen, etc.). Furthermore, when applying the compounds of the present invention to the above-mentioned diseases, they can be used in combination with biological agents (e.g., antibodies, vaccines, etc.), and the compounds can also be combined with gene therapy as a combination therapy. Examples of antibodies and vaccines include angiotensin II vaccines, CETP vaccines, CETP antibodies, TNF-α antibodies, antibodies against other cytokines, amyloid-β vaccines, type 1 diabetes vaccines (such as DIAPEP-277 from Peptor Ltd.), anti-HIV antibodies, HIV vaccines, antibodies and vaccines against cytokines, renin-angiotensin enzymes and their products, vaccines against enzymes and proteins involved in blood lipid metabolism, vaccines against enzymes and proteins involved in the coagulation and fibrinolysis system, and antibodies and vaccines against proteins involved in glucose metabolism and insulin resistance. In addition, combinations with biological agents involved in growth factors, such as GH and IGF, are possible. Gene therapies that can be specifically mentioned include treatment methods using genes related to cytokines, renin-angiotensin enzymes and their products, G proteins, G protein-coupled receptors and their phosphorylation enzymes; treatment methods using DNA decoys, such as NFκB decoys; treatment methods using antisense; treatment methods using genes related to enzymes and proteins involved in blood lipid metabolism (e.g., genes involved in the metabolism, excretion, and absorption of cholesterol or triglycerides or HDL-cholesterol or blood phospholipids); treatment methods using genes related to enzymes and proteins involved in angiogenesis therapy aimed at peripheral vascular occlusion (e.g., growth factors, such as HGF and VEGF); treatment methods using genes related to proteins involved in glucose metabolism and insulin resistance; and antisense against cytokines, such as TNF-α. Furthermore, compounds can be used in combination with cell transplantation therapies using tissue engineering, such as those for various organ regeneration methods, such as cardiac regeneration, kidney regeneration, pancreatic regeneration, and vascular regeneration, 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).

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

[0198] Hereafter, the compounds and concomitant drugs of the present invention used in combination will be referred to as "the combination agents of the present invention." When using the combination agent 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 its pharmaceutical composition and the concomitant drug or its pharmaceutical composition may be administered to the subject simultaneously or at different times. The dosage of the concomitant drug can be determined according to clinically used dosages and may be appropriately selected depending on the subject, route of administration, disease, combination, etc. The method of administering the concomitant drugs of the present invention is not particularly limited; it is sufficient that the compounds and concomitant drugs of the present invention are administered in combination. Examples of such administration methods include the following: (1) Administration of a single formulation obtained by simultaneous processing of the compound of the present invention and a concomitant drug; (2) Simultaneous administration of two formulations of the compound of the present invention and a concomitant drug, which are manufactured separately, via the same route of administration; (3) Shifted administration of two formulations of the compound of the present invention and a concomitant drug, which are manufactured separately, via the same route of administration; (4) Simultaneous administration of two formulations of the compound of the present invention and a concomitant drug, which are manufactured separately, via different routes of administration; (5) Shifted administration of two formulations of the compound of the present invention and a concomitant drug, which are manufactured separately, via different routes of administration (for example, administration of the compound of the present invention and the concomitant drug in order or in reverse order).

[0199] The combination agents of the present invention exhibit low toxicity. For example, the compounds of the present invention and / or the above-mentioned combination agents can be combined with pharmacologically acceptable carriers according to known methods for the manufacture of pharmaceutical compositions to produce, for example, tablets (including sugar-coated and film-coated tablets), powders, granules, capsules (including soft capsules), liquids, injections, suppositories, sustained-release agents, etc. These compositions can be safely administered orally or parenterally (e.g., topically, rectally, intravenously, etc.). Injectable agents can be administered intravenously, intramuscularly, subcutaneously, or intra-organally, or directly to the lesion. Examples of pharmacologically acceptable carriers useful in the production of the combination formulations of the present invention include various organic or inorganic carrier materials conventionally used as pharmaceutical materials. For solid formulations, for example, additives, lubricants, binders, and disintegrants may be used. For liquid formulations, for example, solvents, solubilizers, suspending agents, isotonic agents, buffers, sedatives, etc., may be used. When necessary, appropriate amounts of conventional preservatives, antioxidants, colorants, sweeteners, adsorbents, wetting agents, etc., may be used as appropriate. Examples of additives include lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, and light anhydrous silicic acid. Examples of lubricants include magnesium stearate, calcium stearate, talc, and colloidal silica. Examples of binders include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, starch, sucrose, gelatin, methylcellulose, and sodium carboxymethylcellulose. Examples of disintegrants include starch, carboxymethylcellulose, carboxymethylcellulose calcium, sodium carboxymethyl starch, and L-hydroxypropylcellulose. Examples of solvents include injectable water, alcohol, propylene glycol, macrogol, sesame oil, corn oil, and olive oil. Examples of solubilizers include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, and sodium citrate. Examples of suspending agents include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glyceryl monostearate; and hydrophilic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose.

[0200] Examples of isotonic agents include glucose, D-sorbitol, sodium chloride, glycerin, and D-mannitol. Examples of buffering agents include buffer solutions such as phosphoric acid, acetic acid, carbonic acid, and citric acid. Examples of sedatives include benzyl alcohol. Examples of preservatives include p-oxybenzoate, chlorobutanol, benzyl alcohol, phenylethyl alcohol, dehydroacetic acid, and sorbic acid. Examples of antioxidants include sulfites, ascorbic acid, and α-tocopherol.

[0201] The mixing ratio of the compound of the present invention to the co-administered drug in the combination agent of the present invention can be appropriately selected depending on the target of administration, route of administration, disease, etc. 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 co-administered drug 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 additives, such as carriers, in the combination agent of the present invention varies depending on the form of the formulation, and is usually about 1 to about 99.99 wt%, preferably about 10 to about 90 wt%, based on the formulation. When the compound and concomitant drug of the present invention are formulated separately into pharmaceutical formulations, their content is similar to that described above. [Examples]

[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 approximately 10°C to approximately 35°C. Unless otherwise specified, the ratio of solvent mixtures is a volume ratio. Unless otherwise specified, % means wt%. Unless otherwise specified, elution by column chromatography in the examples was performed under observation by TLC (thin-layer chromatography). A Merck 60F was used for TLC observation. 254The TLC plate was used, and the solvent used as the elution solvent in column chromatography was used as the developing solvent. A UV detector was used for detection. In silica gel column chromatography, NH indicates aminopropylsilane-bonded silica gel, and diol indicates the use of 3-(2,3-dihydroxypropoxy)propylsilane-bonded silica gel. In preparative HPLC (high-performance liquid chromatography), C18 indicates the use of octadecyl-bonded silica gel. Unless otherwise specified, the ratios shown for the elution solvents are volume mixing ratios. 1 For 1H NMR analysis, software such as ACD / SpecManager (product name) was used. Peaks of hydroxyl groups, amino groups, etc., which have extremely weak protons, may not be shown. MS was measured by LC / MS. ESI or APCI methods were used for ionization. The data shown are actual measured values. Generally, molecular ion peaks are observed, and they may also be observed as fragment ions. In the case of salts, molecular ion peaks or fragment ion peaks in the free form are generally observed. Optical rotation ([α] D The sample concentration (c) for this purpose is in units of g / 100mL. Elemental analysis values ​​(Anal.) are listed as both calculated values ​​(Calcd) and actual measured values ​​(Measured values). The peaks obtained by powder X-ray diffraction in the examples refer to the peaks measured at room temperature using Ultima IV (Rigaku Corporation, Japan) with Cu Kα radiation as the feed filter. The measurement conditions are as follows: Voltage / Current: 40kV / 50mA Scanning speed: 6 degrees / minute 2-theta scanning range: 2-35 degrees The degree of crystallinity in the examples was calculated using the Hermann method based on powder X-ray diffraction. 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 1H NMR: Proton Nuclear Magnetic Resonance LC / M: Liquid Chromatography Mass Spectrometer TLC: Thin-layer chromatography ESI: Electrospray ionization, electron spray ionization APCI: Atmospheric pressure chemical ionization Acetic acid (TOH) Boc:tert-butoxycarbonyl (Boc)2O: Ditert-butyl dicarbonate (Bpin)2: Bis(pinacolato) diboron br:Broad singlet n-BuOH: n-butanol n-BuLi: n-butyllithium 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 æ: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 Methoxyde 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(diphenylphosphin)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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidine-3-yl]-N-[2-(diethylamino)ethyl]benzamide

[0204] A) Methyl(2S)-2-(5-bromo-2-cyanophenoxy)pupanoate A mixture of 4-bromo-2-hydroxybenzonitrile (14.5 g), methyl(2R)-2-hydroxypupanoate (15.3 g), PPh3 (57.6 g), and THF (150 mL) was mixed with 120 mL of 2.2 M dead toluene solution 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 phenylethylamine. 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 (phenylethylamine / hexane) to obtain 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 72.0 g of methyl(2S)-2-(5-bromo-2-cyanophenoxy)pupanoate was added to a mixture of MeOH (200 mL) and THF (100 mL) with NaBH4 (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 NH4Cl aqueous solution at 0°C and concentrated under reduced pressure. The residue was extracted with HCl. 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 (HCl / hexane) to obtain 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)propylmethanesulfonate 4-Bromo-2-(((2S)-1-hydroxypropan-2-yl)oxy)benzonitrile (21.0 g) and TEA (23 mL) were dissolved in THF (100 mL), to which MsCl (8.9 mL) was added 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 RINKAN. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was filtered through an NH silica pad and concentrated under reduced pressure to obtain 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-tetrazole-1-yl)propan-2-yl)oxy)benzonitrile (2S)-2-(5-bromo-2-cyanophenoxy)propylmethanesulfonate (25.0 g), 1H-tetrazole (10.5 g), and DMF (100 mL) were mixed with K2CO3 (20.7 g) at room temperature, and the mixture was stirred overnight at 80°C. The mixture was diluted with water at room temperature and extracted with ethyl acetate. 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 (ethyl acetate / hexane) to obtain 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-tetrazole-1-yl)propane-2-yl)oxy)benzonitrile 4-bromo-2-{[(2S)-1-(1H-tetrazole-1-yl)propan-2-yl]oxy}benzonitrile (5.00 g), (Bpin)2 (4.52 g), KOAc (7.93 g), and DMF (50 mL) were mixed with Pd(dppf)Cl2-CH2Cl2 (594 mg). After stirring at 100°C for 4 hours under a nitrogen atmosphere, the mixture was poured into water and extracted with ethyl acetate. 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 (ethyl acetate / hexane) to obtain the title compound (3.30 g). MS m / z 356.2 [M+H] +

[0209] F) 4-{pyrazolo[1,5-a]pyrimidine-5-yl}-2-{[(2S)-1-(1H-tetrazole-1-yl)propan-2-yl]oxy}benzonitrile 5-Chloropyrazolo[1,5-a]pyrimidine (120 mg), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{[(2S)-1-(1H-tetrazole-1-yl)propan-2-yl]oxy}benzonitrile (666 mg), and Cs2CO3 (508 mg) are dissolved in THF (10 mL) and water (2.0 mL) and Pd( tBu3P)2 (39.9 mg) was added, and the mixture was stirred at 70°C for 10 hours under a nitrogen atmosphere. The mixture was quenched with water at room temperature and extracted with toluene. 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, toluene / hexane) to obtain 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]pyrimidine-5-yl}-2-{[(2S)-1-(1H-tetrazole-1-yl)propan-2-yl]oxy}benzonitrile 4-{pyrazolo[1,5-a]pyrimidine-5-yl}-2-{[(2S)-1-(1H-tetrazole-1-yl)propan-2-yl]oxy}benzonitrile (180 mg) was added to a mixture in DMF (5.0 mL) with 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 NaHCO3 aqueous solution at 0°C and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure to obtain 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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidine-3-yl]benzoate A mixture of 4-{3-bromopyrazolo[1,5-a]pyrimidine-5-yl}-2-{[(2S)-1-(1H-tetrazole-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) with Cs2CO3 (252 mg) and Pd( t Bu3P)2 (26.4 mg) was added, and the mixture was stirred at 80°C for 14 hours under a nitrogen atmosphere. The mixture was quenched with water at room temperature and extracted with toluene. 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, toluene / hexane) to obtain 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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidine-3-yl]benzoic acid A mixture of methyl 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidine-3-yl]benzoate (150 mg) in MeOH (10 mL) and THF (10 mL) was mixed with 2 M NaOH aqueous solution (0.16 mL). The mixture was stirred under a nitrogen atmosphere at 50°C for 10 hours. The mixture was acidified with 6 M HCl aqueous solution (pH 2-3). The precipitate was collected by filtration and dried under reduced pressure to obtain 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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidine-3-yl]-N-[2-(diethylamino)ethyl]benzamide 3-[5-(4-cyano-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)pyrazolo[1,5-a]pyrimidine-3-yl]benzoic acid (145 mg), WSC-HCl (178 mg), and HOBt-H2O (125 mg) were mixed in DMF (5.0 mL) with (2-aminoethyl)diethylamine (72.2 mg) and TEA (0.13 mL). The mixture was stirred under a nitrogen atmosphere for 16 hours. The mixture was quenched with water at room temperature and extracted with butyl. 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, butyl / hexane), followed by preparative HPLC (water containing 0.1% TFA / CH3CN). The desired fraction was azeotropically mixed with toluene under reduced pressure. Dissolve the residue in MeOH (5.0 mL) and Amberlyst (登録商標) A21 was added to the mixture. The mixture was stirred at room temperature for 15 minutes, and then insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure to obtain 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]pyrimidine-5-yl]phenoxy}propyl]-1H-tetrazol

[0215] A) Methyl(2S)-2-(5-bromo-2-fluorophenoxy)pupanoate 5-bromo-2-fluorophenol (74.0 g), methyl (2R)-2-hydroxypupanoate (80.7 g), and PPh3 (152 g) were dissolved in THF (1000 mL), to which DIAD (118 g) was gradually added at 0°C. The mixture was stirred under a nitrogen atmosphere at 25°C for 12 hours. The mixture was diluted with water (1000 mL) and extracted with HCl (800 mL x 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 (HCl / PE) to obtain 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)propane-1-ol 85.0 g of methyl(2S)-2-(5-bromo-2-fluorophenoxy)pupanoate was dissolved in 330 mL of THF and 660 mL of MeOH, to which 17.4 g of NaBH4 was gradually added over 0.5 hours at 0°C. The mixture was stirred under a nitrogen atmosphere at 25°C for 12 hours. The mixture was diluted at 0°C with 500 mL of saturated NH4Cl aqueous solution and 500 mL of water. The organic solvent was removed under reduced pressure. The residue was extracted with HCl (400 mL x 3). The combined organic layers were washed with brine (800 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (HCl / PE) to obtain 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 = 6.0Hz, 3H)

[0217] C) (2S)-2-(5-bromo-2-fluorophenoxy)propylmethanesulfonate (2S)-2-(5-bromo-2-fluorophenoxy)propan-1-ol (75.0 g) and TEA (60.9 g) were dissolved in THF (1000 mL), to which MsCl (48.3 g) was added dropwise at 0°C. The mixture was stirred under a nitrogen atmosphere at 25°C for 1 hour. The mixture was diluted with water (800 mL) and extracted with HCl (1000 mL x 3). The combined organic layers were washed with brine (800 mL), dried over Na2SO4, and concentrated under reduced pressure to obtain 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-tetrazol A mixture of (2S)-2-(5-bromo-2-fluorophenoxy)propylmethanesulfonate (97.0 g) and 1H-tetrazole (41.5 g) in DMF (1000 mL) was mixed with K2CO3 (82.0 g). The mixture was stirred at 80°C for 12 hours. The mixture was diluted with saturated NH4Cl aqueous solution (600 mL) and extracted with HCl (200 mL x 3). The combined organic layer was washed with brine (600 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (HCl / PE) to obtain 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-tetrazol A mixture of 1-[(2S)-2-(5-bromo-2-fluorophenoxy)propyl]-1H-tetrazole (29.3 g), (Bpin)2 (37.1 g), Pd(dppf)Cl2-CH2Cl2 (7.95 g), and KOAc (19.1 g) in DMSO (300 mL) was stirred at 100°C for 2 hours under a nitrogen atmosphere. The mixture was diluted with water (300 mL) and extracted with HCl (300 mL x 3). The combined organic layer was washed with brine (300 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (HCl / PE) to obtain 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]pyrimidine-5-yl}phenoxy)propyl]-1H-tetrazol The reaction and purification were carried out according to Step F of Example 1 to obtain 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]pyrimidine-5-yl}-2-fluorophenoxy)propyl]-1H-tetrazol The reaction and purification were carried out according to Step G of Example 1 to obtain 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]pyrimidine-5-yl]phenoxy}propyl]-1H-tetrazol The reaction and purification were carried out according to Step H of Example 1 to obtain 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]pyrimidine-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]propane-1-ol A mixture of (2S)-2-(3-bromophenoxy)propan-1-ol (35.0 g), (Bpin)2 (45.9 g), and KOAc (44.3 g) in toluene (100 mL) was mixed with Pd(dppf)Cl2 (5.53 g). After stirring at 100°C for 3 hours under an argon atmosphere, the mixture was poured into water and extracted with phenyl. 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 (phenyl / hexane) to obtain the title compound (36.0 g). MS m / z 279.1 [M+H] +

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

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

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

[0228] E) (2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidine-5-yl]phenoxy}propylmethanesulfonate (2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidine-5-yl]phenoxy}propan-1-ol (1.80 g) and TEA (777 mg) were mixed in THF (10 mL) and MsCl (644 mg) was added. The mixture was stirred at room temperature for 30 minutes. The mixture was poured into water and extracted with SiO2. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure to obtain 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]pyrimidine-5-yl]phenoxy}propyl]-1H-1,2,4-triazole (2S)-2-{3-[3-(thiophen-2-yl)pyrazolo[1,5-a]pyrimidine-5-yl]phenoxy}propylmethanesulfonate (100 mg) and K2CO3 (64.3 mg) in DMF (5.0 mL) were mixed with 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 ethyl acetate. 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, ethyl acetate / hexane) to obtain 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-tetrazole-1-yl)propane-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-tetrazol 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) were dissolved in THF (320 mL) and water (80 mL) to which Cs2CO3 (61.8 g) and Pd(dppf)Cl2-CH2Cl2 (7.74 g) were added. The mixture was stirred at 70°C for 1 hour under a nitrogen atmosphere. The mixture was diluted with water (300 mL) and extracted with HCl (400 mL x 3). The combined organic layer was washed with brine (500 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (MeOH / HCl) to obtain 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-tetrazol 1-[(2S)-2-(2-fluoro-5-{imidazo[1,2-b]pyridazin-6-yl}phenoxy)propyl]-1H-tetrazole (20.0 g) was added to a mixture in DMF (300 mL) with NBS (10.5 g). The mixture was stirred under a nitrogen atmosphere at 25°C for 12 hours. The mixture was diluted with water (200 mL) and extracted with RINKAN (300 mL x 3). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (RINKAN) to obtain 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-tetrazole-1-yl)propane-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 for 1 hour under a nitrogen atmosphere. The mixture was poured into water and extracted with butyl. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was crystallized from butyl to obtain 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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridine-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 A mixture of 5-chloro-3H-imidazo[4,5-b]pyridine (3.90 g) and DIPEA (6.53 g) in DMF (40 mL) was mixed with SEMCl (3.6 mL). After stirring at 80°C for 14 hours under a nitrogen atmosphere, an 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 HCl. 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, HCl / hexane) to obtain a mixture of the title compound (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]pyridine-5-yl)phenoxy]propyl]-1H-tetrazol and 1-[(2S)-2-[2-fluoro-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazo[4,5-b]pyridine-5-yl)phenoxy]propyl]-1H-tetrazol The reaction and purification were carried out according to Step D of Example 284 to obtain the title compound. MS m / z 470.3 [M+H] +

[0237] C) 1-[(2S)-2-(2-fluoro-5-{3H-imidazo[4,5-b]pyridine-5-yl}phenoxy)propyl]-1H-tetrazol A mixture of 1-[(2S)-2-[2-fluoro-5-(3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridine-5-yl)phenoxy]propyl]-1H-tetrazole and 1-[(2S)-2-[2-fluoro-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazo[4,5-b]pyridine-5-yl)phenoxy]propyl]-1H-tetrazole (7.48 g) in THF (40 mL) was mixed with 14 mL of 1 M TBAF THF solution. The mixture was stirred at 80°C for 4 hours under a nitrogen atmosphere. The mixture was quenched with water at room temperature and extracted with ELISA. The organic layer was separated, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure to obtain 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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridine-3-yl]pyridine-3-carbonitrile A mixture of 1-[(2S)-2-(2-fluoro-5-{3H-imidazo[4,5-b]pyridine-5-yl}phenoxy)propyl]-1H-tetrazole (250 mg), 2-chloropyridine-3-carbonitride (152 mg), K3PO4 (233 mg), tBuXPhos (62.5 mg), and Pd2(dba)3 (67.4 mg) in DMA (15 mL) was stirred at 100°C for 1 hour under microwave irradiation. The mixture was quenched with water at room temperature and extracted with ethyl acetate. 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 (ethyl acetate / hexane) and silica gel column chromatography (NH₃, ethyl acetate / hexane) to obtain 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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridine-3-yl]-1-methyl-1H-imidazole-5-carbonitrile

[0240] A) 4-[(6-chloro-3-nitropyridine-2-yl)amino]-1-methyl-1H-imidazole-5-carbonitrile The reaction and purification were carried out according to Step A of Example 284 to obtain 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]pyridine-3-yl}-1-methyl-1H-imidazole-5-carbonitrile The reaction and purification were carried out according to steps B and C of Example 284 to obtain the title compound. MS m / z 259.1 [M+H] +

[0242] C) 4-[5-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridine-3-yl]-1-methyl-1H-imidazole-5-carbonitrile The reaction and purification were carried out according to Step D of Example 284 to obtain 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-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile

[0244] A) Methyl(2S)-2-(3-bromophenoxy)pupanoate 75.0 g of 3-bromophenol, 90.3 g of methyl (2R)-2-hydroxypupanoate, and 171 g of PPh3 in 1000 mL of THF were mixed with 131 g of DIAD at 0°C. The mixture was stirred at 20°C for 12 hours under a nitrogen atmosphere. The mixture was diluted with 1000 mL of water and extracted with HCl (500 mL x 3). The combined organic layer was washed with 1000 mL of brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was ground with 15% HCl in 500 mL of PE and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (HCl / PE) to obtain 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)propane-1-ol 41.0 g of methyl(2S)-2-(3-bromophenoxy)pupanoate was added gradually to a mixture of THF (200 mL) and MeOH (400 mL) with 8.98 g of NaBH4 at 0°C. The mixture was stirred at 20°C for 12 hours under a nitrogen atmosphere. 500 mL of saturated NH4Cl aqueous solution and 500 mL of water were added to the mixture at 0°C. The organic solvent was removed under reduced pressure. The residue was extracted with SiO4 (400 mL x 3). The combined organic layers were washed with brine (800 mL), dried over Na2SO4, and concentrated under reduced pressure to obtain 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)propylmethanesulfonate A mixture of (2S)-2-(3-bromophenoxy)propan-1-ol (64.0 g) and TEA (56.1 g) in THF (700 mL) was mixed with MsCl (44.4 g) dropwise at 0°C for 0.5 hours. The mixture was stirred under a nitrogen atmosphere at 20°C for 1 hour. The mixture was diluted with water (1000 mL) and extracted with SiO (500 mL x 3). The combined organic layers were washed with brine (1000 mL), dried over Na2SO4, filtered, and c...

Claims

1. Equation (I): 【Chemistry 1】 [During the ceremony, X １ is N or CR Ｘ１ And here, R Ｘ１ is a hydrogen atom, halogen atom or C １－６ It is an alkyl group; X ２ 、 X ３ and X ４ are each independently C or N, and one of X ２ 、 X ３ and X ４ is N and the other two are C; X ５ is N or CR Ｘ５ And here, R Ｘ５ is a hydrogen atom; X ６ is N or CR Ｘ６ And here, R Ｘ６ is a hydrogen atom; Ring A １ C is sometimes further replaced ６－１４ Aromatic hydrocarbons, optionally further substituted aromatic heterorings, or optionally further substituted non-aromatic heterorings, each optionally fused with an optionally substituted five-membered or six-membered ring; Y １ is N or CR Ｙ１ And here, R Ｙ１ is a hydrogen atom; Y ２ is N or CR Ｙ２ And here, R Ｙ２ is a hydrogen atom, a halogen atom, or a cyano group; Y ３ is N or CR Ｙ３ And here, R Ｙ３ is a hydrogen atom or a halogen atom; Y ４ is N or CR Ｙ４ And here, R Ｙ４ is a hydrogen atom or a halogen atom; Ring B １ It is an aromatic heteroring that may be further substituted in some cases; V is O, S, S(O), S(O) ２ or N(R Ｖ ) and here, R Ｖ C is a hydrogen atom or optionally substituted C １－６ It is an alkyl group; and Z is sometimes replaced by C. １－６ It is an alkylene group. Compounds of the compound or its pharmaceutically acceptable salt.

2. A compound or pharmaceutically acceptable salt of claim 1, wherein V is O.

3. Ring B １ The compound or pharmaceutically acceptable salt of claim 1, wherein the compound is a five-membered aromatic heterocycle which may be further substituted in some cases.

4. The compound or pharmaceutically acceptable salt of claim 1, wherein Z is optionally a substituted ethylene group.

5. X ５ A compound or pharmaceutically acceptable salt of claim 1, wherein N is present.

6. X ６ A compound or pharmaceutically acceptable salt of claim 1, wherein is CH.

7. Y １ , Y ２ , Y ３ and Y ４ A compound or pharmaceutically acceptable salt of claim 1, wherein at least one of the elements is N.

8. Equation (I-1): 【Chemistry 2】 [In the formula, each symbol is as defined in Claim 1.] The compound or pharmaceutically acceptable salt according to claim 1, or represented by a pharmaceutically acceptable salt thereof.

9. Formula (II): 【Transformation 3】 [During the ceremony, X １ is N or CR Ｘ１ And here, R Ｘ１ is a hydrogen atom, halogen atom or C １－６ It is an alkyl group; X ２ , X ３ and X ４ Each is independently C or N, and X ２ , X ３ and X ４ One of them is N, and the other two are C; Ring A ２ The rings are, in some cases, further substituted benzene rings, in some cases, further substituted five- or six-membered aromatic heterorings, or in some cases, further substituted five- or six-membered non-aromatic heterorings, each of which is, in some cases, fused with a further substituted five- or six-membered ring; Y １ is N or CR Ｙ１ And here, R Ｙ１ is a hydrogen atom; Y ２ is N or CR Ｙ２ And here, R Ｙ２ is a hydrogen atom, a halogen atom, or a cyano group; Y ３ is N or CR Ｙ３ And here, R Ｙ３ is a hydrogen atom or a halogen atom; Y ４ is N or CR Ｙ４ And here, R Ｙ４ is a hydrogen atom or a halogen atom; Ring B ２ It is a five-membered aromatic heteroring that may be further substituted in some cases; and R １ is C １－６ It is an alkyl group. Compounds of the compound or its pharmaceutically acceptable salt.

10. X １ A compound or pharmaceutically acceptable salt of claim 9, wherein is CH.

11. Ring B ２ The compound or pharmaceutically acceptable salt of claim 9, wherein is a tetrazole or triazole, each bonded at its nitrogen.

12. R １ A compound or pharmaceutically acceptable salt of claim 9, wherein is methyl.

13. Ring A ２ The compound or pharmaceutically acceptable salt of claim 9, wherein is a benzene ring, a six-membered aromatic heterocycle, or a six-membered non-aromatic heterocycle, each of which is further substituted with one cyano group, and optionally further substituted.

14. Y １ , Y ２ , Y ３ and Y ４ A compound or pharmaceutically acceptable salt of claim 9, wherein at least one of the atoms is N.

15. Formula (II-1): 【Chemistry 4】 [In the formula, each symbol is as defined in claim 9.] The compound or pharmaceutically acceptable salt according to claim 9, or represented by a pharmaceutically acceptable salt thereof.

16. Formula (III): 【Transformation 5】 X ２ , X ３ and X ４ Each is independently C or N, and X ２ , X ３ and X ４ One of them is N, and the other two are C; Ring A ３ This is a benzene ring which may be further substituted, a six-membered nitrogen-containing aromatic heteroring which may be further substituted, or a six-membered nitrogen-containing non-aromatic heteroring which may be further substituted; Y １ is N or CR Ｙ１ And here, 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 And here, R Ｙ３ is a hydrogen atom or a halogen atom; Y ４ is N or CR Ｙ４ And here, R Ｙ４ is a hydrogen atom or a halogen atom; and W is either N or CH. Compounds of the compound or its pharmaceutically acceptable salt.

17. formula; 【Transformation 6】 The partial structure represented by is formula (A ３ -1) to (A ３ -9); 【Transformation 7】 [During the ceremony, Q １ is N or CR Ｑ１ And here, R Ｑ１ teeth (a) Hydrogen atom, (b) Cyano group, (c) Halogen atom, (d) Hydroxyl group, (e) Carboxy group, (f) Amino group, (g) C which may be substituted in some cases １－６ alkyl group, (h) C which is replaced in some cases １－６ Alkoxy group, (i) C １－６ Alkyl-carbonyl group, (j) C １－６ Alkoxy-carbonyl group, (k) Mono- or G-C which may be substituted depending on the case １－６ Alkylamino group, (l) Mono- or G-C which may be substituted depending on the case １－６ Alkyl-carbonylamino group, (m) Mono or G-C １－６ Alkoxy-carbonylamino group, (n) Mono- or G-C １－６ Alkyl-carbamoyl group, (o) G-C １－６ Alkyl sulfinylidene amino group, (p) C ３－１０ Cycloalkyl groups, (q) C which is replaced in some cases ３－１０ Cycloalkyloxy group, (r) 3-8 member monocyclic non-aromatic heterocyclic group, (s) A 3- to 8-membered monocyclic non-aromatic heterocyclyloxy that may be substituted in some cases. (t) A 3- to 8-membered monocyclic non-aromatic heterocyclyl carbonyl group which may be substituted in some cases. (u) 3-8 membered monocyclic non-aromatic heterocyclideneamino group, Q ２ is N or CR Ｑ２ And here, R Ｑ２ teeth (a) Hydrogen atom, (b) Halogen atom or (c) C １－６ Alkoxy group, Q ３ is N or CR Ｑ３ , and here, R Ｑ３ teeth (a) Hydrogen atom, (b) Cyano group, (c) Halogen atom, (d) Carboxylic group, (e) C which is replaced in some cases １－６ alkyl group, (f) C which is replaced in some cases １－６ Alkoxy group, (g) C １－６ Alkyl-carbonyl group, (h) C １－６ Alkoxy-carbonyl group, (i) Mono or G-C １－６ Alkylamino group, (j) Mono- or G-C which may be substituted depending on the case １－６ Alkyl-carbamoyl group, (k) G-C １－６ Alkyl sulfinylidene amino group or (l) 3- to 8-membered monocyclic non-aromatic heterocyclidene amino group And, Q ４ is N or CR Ｑ４ , and here, R Ｑ４ teeth (a) A hydrogen atom or (b) Halogen atom And Q １ Q ２ Q ３ and Q ４ The N atoms are oxidized in each case; R Ｎ１ is a hydrogen atom or C １－６ It is an alkyl group; R Ｎ２ is a hydrogen atom or C １－６ It is an alkyl group; R Ｎ３ is a hydrogen atom or C １－６ It is an alkyl group; and R Ｎ４ C is substituted with hydrogen atoms or, in some cases, 1 to 3 halogen atoms. １－６ It is an alkyl group. A compound or pharmaceutically acceptable salt of claim 16, represented by [the specified formula].

18. Y １ , Y ２ , Y ３ and Y ４ A compound or pharmaceutically acceptable salt of claim 16, wherein at least one of the atoms is N.

19. Formula (III-1): 【Transformation 8】 [In the formula, each symbol is as defined in claim 16.] The compound or pharmaceutically acceptable salt according to claim 16, or represented by a pharmaceutically acceptable salt thereof.

20. 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propan-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]pyridine-3-carbonitrile, 2-[6-(3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]pyridine-3-carbonitrile, 2-[5-(3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)-3H-imidazo[4,5-b]pyridine-3-yl]pyridine-3-carbonitrile, 4-Fluoro-2-[6-(5-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-3-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, 4-Methoxy-2-[6-(3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]pyridine-3-carbonitrile, 2-[6-(4-fluoro-3-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}phenyl)imidazo[1,2-b]pyridazine-3-yl]-4-methoxypyridine-3-carbonitrile, 4-Fluoro-2-[5-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)-3H-imidazo[4,5-b]pyridine-3-yl]benzonitrile, 4-Fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyrazine-2-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, 4-Fluoro-2-methoxy-6-[5-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)-3H-imidazo[4,5-b]pyridine-3-yl]benzonitrile and 4-Fluoro-2-methoxy-6-[6-(6-{[(2S)-1-(1H-tetrazole-1-yl)propane-2-yl]oxy}pyridine-2-yl)imidazo[1,2-b]pyridazine-3-yl]benzonitrile, A salt selected from the group consisting of, or a pharmaceutically acceptable salt.

21. A pharmaceutical product comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.

22. The pharmaceutical product according to claim 21, which is a calcium / calmodulin-dependent protein kinase II inhibitor.

23. The pharmaceutical product according to claim 21, which is a drug for the prevention or treatment of heart disease.

24. The pharmacopoeia of claim 23, wherein the heart disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmias.

25. A compound or pharmaceutically acceptable salt of claim 1 for use in the prevention or treatment of heart disease.

26. The compound or pharmaceutically acceptable salt of claim 25, wherein the cardiac disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmias.

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

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

29. The method of claim 28, wherein the heart disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmias.

30. Use of the compound or pharmaceutically acceptable salt of claim 1 for the manufacture of an agent for the prevention or treatment of heart disease.

31. Use of claim 30, wherein the cardiac disease is selected from catecholamine-induced polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, and fatal arrhythmias.

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