Spiro compounds

Abstract

The invention relates to a pharmacologically acceptable spiro compound or its salt which has TRH-DE (thyrotropin-degrading enzyme-releasing hormone) inhibitory activity and is useful for the prevention or treatment of various diseases associated with TRH and / or its associated symptoms, a method for the preparation of such compound, its application, and a pharmaceutical composition containing the pharmacologically acceptable compound or its salt as the active ingredient.The invention relates to a compound represented by Formula [I]: wherein ring A represents a substitutable aryl group, a substitutable heteroaryl group, or a substitutable fatty heterocyclyl group, and R1 and R2 represent, independently, a substitutable alkyl group, a substitutable cycloalkyl group, a substitutable alkenyl group, a substitutable cycloalkenyl group, a substitutable alkynyl group, a substitutable aryl group, a substitutable heteroaryl group, a substitutable fatty heterocyclyl group and possibly a double bond in part of the ring, a substitutable amino group, a substitutable alkoxy group, or a substitutable alkylthio group, or a group in which R1 and R2 together form a ring, or its pharmacologically acceptable salt.

Description

Novel spiro compounds

[0001] The present invention relates to novel spiro compounds that have an inhibitory effect on thyrotropin-releasing hormone (hereinafter also referred to as "TRH")-degrading ectoenzyme (hereinafter also referred to as "TRH-DE"; also known as pyroglutamyl aminopeptidase II, also referred to as "PAP-II" or "PP-II"), which is a thyrotropin-releasing hormone (hereinafter also referred to as "TRH")-degrading enzyme, and are useful for the prevention and / or treatment of various diseases and / or associated symptoms thereof that can be improved by increasing central TRH levels.

[0002] TRH is a peptide composed of three amino acid residues, pGlu-His-Pro-NH2, isolated as a hypothalamic hormone. TRH exerts its effects by binding to TRH receptors present on the cell membrane of target cells, while undergoing quantitative regulation at each stage of synthesis, secretion, and degradation. In peripheral tissues, it primarily promotes the synthesis and secretion of anterior pituitary hormones, thyroid-stimulating hormone (TSH) and prolactin, contributing to increased respiratory volume / energy production and mammary gland development. Meanwhile, TRH also plays a role in central tissues, where it is known to exhibit various physiological activities, such as acting as a central activator by regulating the production of neurotransmitters in the nervous system. Therefore, quantitative control of TRH has attracted attention as a method for improving various TRH-related diseases and / or their associated symptoms.

[0003] TRH-DE, a TRH-degrading enzyme, is a zinc-metalloprotease that hydrolyzes the pyroglutamyl-histidyl peptide bond of TRH. It is a membrane-bound enzyme consisting of a large extracellular domain containing the catalytic site, a transmembrane domain, and a small intracellular domain. TRH-DE is highly expressed in the brain and therefore plays a major role in the degradation of TRH in the synaptic cleft of neurons. Other enzymes involved in TRH degradation include pyroglutamyl-peptidase I (EC 3.4.19.3, also referred to as "PP I" hereafter) and prolyl oligopeptidase (EC 3.4.21.26, also referred to as "POP" hereafter). PP I and POP are also expressed in various peripheral tissues (Non-Patent Documents 1 and 2) and target multiple substrates in addition to TRH. However, TRH-DE can selectively control the degradation of TRH (Non-Patent Document 3). In an evaluation of TRH decomposition activity using rat brain homogenate, it was shown that PP I-specific inhibitors did not have the effect of inhibiting TRH degradation, but TRH-DE-specific inhibitors did (Non-Patent Document 4).

[0004] Known compounds having TRH-DE inhibitory activity include, for example, nucleic acids having sequences that are partially or completely identical to the RNA of TRH-DE (Patent Document 1) and TRH-like peptide derivatives (Patent Documents 2 and 3).

[0005] International Publication No. WO 2007 / 113784 International Publication No. WO 01 / 60843 International Publication No. WO 2006 / 038206

[0006] European Journal of Biochemistry (Eur. J. Biochem.), 1999; 265: pp. 415-422 Peptides, 2003; 24: pp. 1367-1372 Neuropharmacology, 2007; 52: pp. 1472-1481 Biol. Pharm. Bull. 2004; 27(8): pp. 1197-1201

[0007] It has not been reported that spiro compounds such as the compounds of the present invention have TRH-DE inhibitory activity. The present invention relates to novel spiro compounds or pharmacologically acceptable salts thereof that have TRH-DE inhibitory activity. The compounds of the present invention are useful for the prevention and / or treatment of various diseases and / or associated symptoms that can be improved by increasing central TRH levels.

[0008] Specifically, the present invention provides a compound represented by the following formula [I]: [wherein, ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group; R １ and R ２ each represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, an optionally substituted amino group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, or R １ and R ２ represent groups which together form a ring] (hereinafter also referred to simply as compound [I]) or a pharmaceutically acceptable salt thereof.

[0009] In the present invention, the compound of formula [I] is preferably a compound of formula [II], formula [III] or formula [IV] shown below.

[0010] That is, the present invention also provides a compound of the following formula [II]: [wherein ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group, ring B represents an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C represents an optionally substituted and partially hydrogenated aryl group, an optionally substituted and partially hydrogenated heteroaryl group, an optionally substituted cycloalkyl group, or an optionally substituted aliphatic heterocyclic group] (hereinafter also simply referred to as compound [II]) or a pharmaceutically acceptable salt thereof.

[0011] The present invention also provides a compound represented by the following formula [III]: [wherein ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group, and ring D represents an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring] (hereinafter also simply referred to as compound [III]) or a pharmaceutically acceptable salt thereof.

[0012] The present invention also provides a compound represented by the following formula [IV]: [wherein, ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group; R １ represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted amino group, an optionally substituted alkoxy group or an optionally substituted alkylthio group, and ring E represents an optionally substituted aryl group, an optionally substituted heteroaryl group or an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring.] (hereinafter also simply referred to as compound [IV]) or a pharmaceutically acceptable salt thereof.

[0013] The present invention also relates to a method for preventing and / or treating various diseases and / or associated symptoms that can be improved by increasing central TRH levels, which comprises administering to a patient an effective amount of a compound represented by formula [I], [II], [III], or [IV] or a pharmacologically acceptable salt thereof. The present invention also relates to a pharmaceutical composition containing compound [I], [II], [III], or [IV] or a pharmacologically acceptable salt thereof as an active ingredient, and the use of compound [I], [II], [III], or [IV] for the preparation thereof. The present invention also relates to compound [I], [II], [III], or [IV] or a pharmacologically acceptable salt thereof, or a pharmaceutical composition containing them as an active ingredient, for use in the prevention and / or treatment of various diseases and / or associated symptoms that can be improved by increasing central TRH levels. The present invention also relates to a method for preparing compound [I], [II], [III], or [IV] or a pharmacologically acceptable salt thereof.

[0014] The compound [I], [II], [III] or [IV] of the present invention or a pharmacologically acceptable salt thereof has excellent inhibitory activity against TRH-DE, and is therefore useful for the prevention and / or treatment of various diseases and / or symptoms associated therewith that can be improved by increasing the central TRH concentration, such as spinocerebellar degeneration, pain, sleep disorders or other psychiatric / neurological disorders, or for improving the prognosis of these diseases.

[0015] The definitions of each group in this specification can be freely combined unless otherwise specified. In the present invention, alkyl means a group having 1 to 6 carbon atoms (C １～６ ) refers to a linear or branched saturated hydrocarbon group having 1 to 4 carbon atoms (C １～４ ) groups are preferred. Specific examples include methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-amyl, n-pentyl, and n-hexyl. Methyl, ethyl, and n-propyl are particularly preferred.

[0016] Cycloalkyl means a group having 3 to 8 carbon atoms (C ３～８) and adamantyl. Cycloalkyl also includes groups in which two carbon atoms constituting the ring are bridged with an alkylene group to form a bicyclic ring. Specific examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and adamantyl. In particular, cycloalkyl groups having 3 to 7 carbon atoms (C ３～７ ) monocyclic groups are preferred.

[0017] Alkoxy refers to a monovalent group in which the alkyl group is bonded to oxygen, and has 1 to 6 carbon atoms (C １～６ ) straight-chain or branched-chain alkyl-O-, １～４ ) alkyl-O- is preferred. Specific examples include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, and t-butoxy.

[0018] Cycloalkoxy refers to a monovalent group in which the above-mentioned cycloalkyl is bonded to oxygen, and has 3 to 8 carbon atoms (C ３～８ ) monocyclic saturated hydrocarbon groups and adamantyl-O-, ３～７ ) is preferably a monocyclic group —O—. Specific examples include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, etc.

[0019] Alkylene is an alkylene having 1 to 6 carbon atoms (C １～６ ) and a linear or branched saturated hydrocarbon divalent group having 1 to 4 carbon atoms (C １～４ ) groups are preferred. Specific examples include methylene, ethylene, trimethylene, and tetramethylene. Both ends of the alkylene may be substituted on the same carbon, or on two adjacent carbons, or on two non-adjacent carbons.

[0020] Halogen or halo refers to fluorine, chlorine, bromine, iodine, etc. Fluorine, chlorine and bromine are preferred, and fluorine is particularly preferred.

[0021] Haloalkyl means the above alkyl substituted with 1 to 3 halogen atoms, and difluoromethyl, trifluoromethyl, etc. are preferred.

[0022] The term "alkoxyalkyl" means the above alkyl substituted with one or two alkoxy groups, and preferred are methoxymethyl, methoxyethyl, methoxypropyl, and the like.

[0023] Alkanoyl refers to a monovalent group in which the alkyl group is bonded to a carbonyl group, and has 1 to 6 carbon atoms (C １～６ ) straight-chain or branched-chain alkyl-CO—. Specific examples include acetyl, propionyl, pivaloyl, butanoyl, pentanoyl, hexanoyl, and heptanoyl.

[0024] Alkenyl refers to a hydrocarbon group having one or more double bonds at any position of the alkyl group. ２～４ Specific examples thereof include vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, and hexadienyl, with vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, and butadienyl being preferred.

[0025] Cycloalkenyl refers to a monocyclic hydrocarbon group having one or more double bonds at any position of the cycloalkyl. Cycloalkenyl also includes a group in which two carbon atoms constituting the ring are bridged with an alkylene group to form a bicyclic ring. In particular, cycloalkenyls having 3 to 7 carbon atoms (C ３～７ ) is preferred. Specific examples include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like.

[0026] Alkynyl refers to a hydrocarbon group having one or more triple bonds at any position of the alkyl. ２～４ ) groups are preferred. Specific examples include ethynyl, propynyl, butynyl, pentynyl, and hexynyl, with ethynyl, propynyl, and butynyl being preferred.

[0027] The aryl refers to a 6- to 10-membered aromatic hydrocarbon cyclic group, preferably a monocyclic or bicyclic aryl, specifically phenyl and naphthyl, with phenyl being particularly preferred.

[0028] The partially hydrogenated aryl refers to the above aryl which has been partially hydrogenated, and specific examples thereof include dihydrophenyl, cyclohexenyl, indanyl, tetrahydronaphthyl, and the like.

[0029] Thus, optionally partially hydrogenated aryl includes phenyl, naphthyl, tetrahydronaphthyl, cyclohexenyl, and the like.

[0030] Heteroaryl refers to a 5- to 10-membered aromatic heterocyclic group containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, and is preferably a monocyclic or bicyclic heteroaryl. More preferably, it is a 5- to 10-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Specific examples include pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyl, indolyl, isoindolyl, indazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, quinolyl, isoquinolyl, imidazopyridyl, and benzopyranyl. Among specific heteroaryls, pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyl, etc. are preferred, and particularly preferred are pyrrolyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidinyl, etc. Among specific heteroaryls, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyl, etc. are also preferred.

[0031] The partially hydrogenated heteroaryl refers to the above heteroaryl which is partially hydrogenated, and specific examples thereof include dihydropyridyl, tetrahydropyridyl, and tetrahydropyridazinyl.

[0032] Thus, optionally partially hydrogenated heteroaryls include pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyl, indolyl, isoindolyl, indazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, quinolyl, isoquinolyl, imidazopyridyl, benzopyranyl, dihydropyridyl, tetrahydropyridyl, tetrahydropyridazinyl, and the like, including pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyl, dihydropyridyl, tetrahydropyridazinyl, and the like.

[0033] For example, in the general formula [I], [II], [III], or [IV], the heteroaryl in the optionally substituted heteroaryl group represented by ring A is preferably thienyl, pyrazolyl, pyridyl, etc., with thienyl and pyridyl being particularly preferred. In addition, in the general formula [II], the optionally partially hydrogenated heteroaryl in the optionally substituted heteroaryl group represented by ring C is preferably pyrrolyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidinyl, dihydropyridyl, tetrahydropyridyl, tetrahydropyridazinyl, etc. In another embodiment, the heteroaryl in the optionally substituted heteroaryl group represented by ring E in the general formula [IV] is preferably pyridyl, azaindolyl, imidazopyridyl, benzimidazolyl, etc.

[0034] The aliphatic heterocycle refers to a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic group containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Bicyclic aliphatic heterocyclic groups include those in which a cycloalkyl or an aliphatic heterocycle is fused to an aliphatic heterocycle or bonded via a spiro atom. Specific examples include azetidinyl, oxetanyl, oxolanyl, azolidinyl, thiolanyl, oxazolidinyl, diazolidinyl, thiazolidinyl, oxanyl, adzinanyl, dioxanyl, oxazinanyl, diazinanyl, thiazinanyl, thianyl, oxepanyl, azepanyl, thiepanyl, oxazepanyl, diazepanyl, and thiazepanyl. Furthermore, those in which these rings are fused to a cycloalkyl or an aliphatic heterocycle or bonded via a spiro atom are also included. Preferred examples include those in which two identical or different aliphatic heterocycles selected from azetidinyl, oxetanyl, oxolanyl, azolidinyl, thiolanyl, oxazolidinyl, diazolidinyl, thiazolidinyl, oxanyl, azinanyl, dioxanyl, oxazinanyl, diazinanyl, thiazinanyl, thianyl, oxepanyl, azepanyl, thiepanyl, oxazepanyl, diazepanyl, thiazepanyl, etc. are fused together or bonded via a spiro atom. Other preferred examples include 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic groups containing at least one nitrogen atom and optionally further containing one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur. Specific examples include azetidinyl, azolidinyl, oxazolidinyl, diazolidinyl, thiazolidinyl, adzinanyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, diazepanyl, and thiazepanyl. Azolidinyl, oxazolidinyl, diazolidinyl, thiazolidinyl, adzinanyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, diazepanyl, and thiazepanyl are preferred, and azolidinyl, diazolidinyl, adzinanyl, oxazinanyl, diazinanyl, azepanyl, oxazepanyl, diazepanyl, and thiazepanyl are more preferred. Further examples include rings in which these rings are fused with a cycloalkyl or an aliphatic heterocycle or bonded via a spiro atom.Particularly preferred are those in which two identical or different aliphatic heterocycles selected from azolidinyl, diazolidinyl, azinanyl, oxazinanyl, diazinanyl, azepanyl, oxazepanyl, diazepanyl, thiazepanyl, etc. are bonded together via a condensed or spiro atom. Examples of the aliphatic heterocycle which may contain a double bond in part of the ring include cyclic groups containing one double bond in the above-mentioned aliphatic heterocycle. Examples include groups in which one of the carbon bonds constituting the ring, such as azinanyl, diazinanyl, and azepanyl, is a double bond. For example, in the general formula [II], the aliphatic heterocyclic moiety of the aliphatic heterocyclic group which may be substituted and contain a double bond in part of the ring, represented by ring B, is preferably azolidinyl, diazolidinyl, azinanyl, oxazinanyl, diazinanyl, azepanyl, oxazepanyl, diazepanyl, thiazepanyl, etc. In addition, in the general formula [II], the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring C is preferably azolidinyl, oxazinanyl, etc. Furthermore, in the general formula [II], the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group selected from the substituents of the group represented by ring C is preferably azolidinyl, adzinanyl, oxazinanyl, diazinanyl, etc. For example, in the general formula [III], the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring D, which may contain a double bond in part of the ring, is preferably azolidinyl, diazolidinyl, adzinanyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, diazepanyl, thiazepanyl, etc.

[0035] In one embodiment of the present invention, in the general formula [I], [II], [III] or [IV], each of the substituents on the optionally substituted aryl group, the optionally substituted heteroaryl group and the optionally substituted aliphatic heterocyclic group represented by ring A is 1 to 3 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, an alkoxyalkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkanoyl group, an alkoxycarbonyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, a sulfonyl group optionally substituted with an alkyl group, an aminocarbonyl group optionally substituted with 1 to 2 alkyl groups, a nitro group, an aryl group and a cycloalkyl group. Another embodiment of the present invention is when each of the substituents on the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A in the general formula [I], [II], [III] or [IV] is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group and a nitro group.

[0036] R １ and R ２ are independently an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, an optionally substituted amino group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, or R １ and R ２ In the general formula [IV], R １ is preferably an optionally substituted alkyl group or an optionally substituted alkenyl group, more preferably an alkyl group, and particularly preferably a propyl group.

[0037] R １ and R ２ The group which forms a ring together with R １and R ２ Any group may be used as long as the nitrogen atoms to which they are bonded together form a ring structure, and this includes not only monocyclic groups but also groups in which multiple rings are bonded. １ and R ２ The group which combines to form a ring may have a substituent. Examples of such a ring include a heteroaryl group which may be substituted or partially hydrogenated, or an aliphatic heterocyclic group which may be substituted and may contain a double bond in part of the ring. Examples of the ring structure of the group in which multiple rings are bonded include a fused ring, a bridged ring, a spiro ring, etc.

[0038] In the general formula [I], R １ and R ２ an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, an optionally substituted amino group, an optionally substituted alkoxy group, an optionally substituted alkylthio group, or R １ and R ２ Each of the substituents in the group that together form a ring may be selected from any substituent. １ and R ２Each of the substituents of the optionally substituted alkyl group, optionally substituted alkenyl group, optionally substituted alkynyl group, optionally substituted alkoxy group, or optionally substituted alkylthio group represented by the formula (I) may be 1 to 8 groups independently selected from the group consisting of an optionally substituted cycloalkyl group, an optionally substituted cycloalkenyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, a halogen atom, a hydroxyl group, an oxo group, a cyano group, an optionally substituted alkoxy group, an optionally substituted cycloalkoxy group, an optionally substituted amino group, an optionally substituted alkylthio group, an optionally substituted alkanoyl group, and an alkoxycarbonyl group. １ and R ２ an optionally substituted cycloalkyl group represented by the formula (I), an optionally substituted cycloalkenyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, an optionally substituted amino group, or R １ and R ２ Each of the substituents of the group which together form a ring may be 1 to 8 groups independently selected from the group consisting of an optionally substituted alkyl group; an optionally substituted cycloalkyl group, an optionally substituted alkenyl group; an optionally substituted cycloalkenyl group; an optionally substituted alkynyl group; an optionally substituted aryl group; an optionally substituted heteroaryl group; an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring; a halogen atom; a hydroxyl group; an oxo group; a cyano group; an optionally substituted alkoxy group; an optionally substituted cycloalkoxy group; an optionally substituted amino group; an optionally substituted alkylthio group; an optionally substituted alkanoyl group; and an alkoxycarbonyl group.

[0039] (1) In one embodiment, the present invention provides a compound represented by the following formula [I]: [wherein, ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group; R １ and R ２ each represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, an optionally substituted amino group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, or R １ and R ２ represent groups which together form a ring] or a pharmacologically acceptable salt thereof.

[0040] (2) In another embodiment, the compound of the formula [I] is a compound of the following formula [II]: [wherein ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group, ring B represents an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C represents an optionally substituted and partially hydrogenated aryl group, an optionally substituted and partially hydrogenated heteroaryl group, an optionally substituted cycloalkyl group, or an optionally substituted aliphatic heterocyclic group] or a pharmaceutically acceptable salt thereof.

[0041] (3) In another embodiment, in the group represented by formula [II], the substituents of the optionally substituted aryl group, the optionally substituted heteroaryl group, and the optionally substituted aliphatic heterocyclic group represented by ring A are 1 to 3 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, an alkoxyalkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkanoyl group, an alkoxycarbonyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, a sulfonyl group optionally substituted with an alkyl group, an aminocarbonyl group optionally substituted with 1 to 2 alkyl groups, a nitro group, and an aryl group, the aryl moiety of the optionally substituted aryl group represented by ring A is a 6- to 10-membered monocyclic or bicyclic aryl, and the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring A is a 5- to 10-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, each of the substituents of the aliphatic heterocyclic group represented by ring B which may be substituted and which may contain a double bond in part of the ring; the aryl group represented by ring C which may be substituted and partially hydrogenated; the heteroaryl group represented by ring C which may be substituted and partially hydrogenated; the cycloalkyl group represented by ring C; and the aliphatic heterocyclic group represented by ring C; is selected from the group consisting of a halogen atom, a hydroxyl group, an oxo group, a cyano group, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkoxy group, a cycloalkoxy group which may be substituted with a cyano group, a haloalkoxy group, an alkylene group which may be substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group which may be substituted with a cycloalkyl group or an aryl group, an aryl group which may be substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group;a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an alkanoyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a cycloalkyl group, an aryl group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkoxycarbonyl group optionally substituted with an aryl group; the aliphatic heterocyclic moiety of the aliphatic heterocyclic group represented by ring B which may be substituted and which may contain a double bond in part of the ring is a 5- to 7-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl moiety of the aryl group represented by ring C which may be substituted and which may be partially hydrogenated is a 6- to 10-membered monocyclic or bicyclic aryl, The compound according to aspect (2) or a pharmacologically acceptable salt thereof includes: the heteroaryl moiety of the optionally substituted and partially hydrogenated heteroaryl group represented by ring C is a 5-10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring C is a 4-9-membered monocyclic or bicyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl group in the selected group in each of the substituents of the group represented by ring B or ring C is a 6-10-membered monocyclic or bicyclic aryl; and the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group in each of the substituents of the group represented by ring B or ring C is a 4-9-membered monocyclic or bicyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. ;

[0042] (4) In yet another embodiment, in the group represented by the formula [II], ring A is an optionally substituted aryl group or an optionally substituted heteroaryl group, the aryl moiety of the optionally substituted aryl group represented by ring A is a 6- to 10-membered monocyclic or bicyclic aryl, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring B and which may contain a double bond in part of the ring is a 5- to 7-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring C is an optionally substituted and partially hydrogenated aryl group, an optionally substituted and partially hydrogenated heteroaryl group, an optionally substituted cycloalkyl group, or an optionally substituted aliphatic heterocyclic group, The aryl moiety of the optionally substituted and partially hydrogenated aryl group represented by Ring C is a 6- to 10-membered monocyclic or bicyclic aryl; the heteroaryl moiety of the optionally substituted and partially hydrogenated heteroaryl group represented by Ring C is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; and the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by Ring C is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur.

[0043] (5) In another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the substituents of the aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, are 1 to 4 groups independently selected from the group consisting of halogen atoms; hydroxyl groups; oxo groups; alkyl groups; haloalkyl groups; alkoxyalkyl groups; alkoxy groups; alkylene groups which may be substituted with 1 to 2 groups independently selected from halogen atoms; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, aryl groups, and alkoxy groups; and alkoxycarbonyl groups which may be substituted with an aryl group; the aliphatic heterocyclic moiety of the aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, is a 5- to 7-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl group in the selected group in the substituent of the group represented by ring B is phenyl; Ring C is an optionally substituted phenyl group, an optionally substituted and partially hydrogenated monocyclic heteroaryl group, an optionally substituted monocyclic cycloalkyl group, or an optionally substituted monocyclic aliphatic heterocyclic group, and each of the substituents of the optionally substituted phenyl group; the optionally substituted and partially hydrogenated monocyclic heteroaryl group; the optionally substituted monocyclic cycloalkyl group; or the optionally substituted monocyclic aliphatic heterocyclic group represented by Ring C is a halogen atom; a hydroxyl group; an oxo group; a cyano group; an alkyl group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkyl group; an alkoxy group;an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of a haloalkoxy group, an alkylene group, an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkanoyl group; Examples of the compound or a pharmacologically acceptable salt thereof according to any one of the above aspects (2) to (4) include: the aliphatic heterocyclic moiety of the optionally substituted monocyclic aliphatic heterocyclic group represented by ring C is a 4- to 7-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aryl group in the selected group in each of the substituents of the group represented by ring C is phenyl, and the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group in each of the substituents of the group represented by ring C is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur;

[0044] (6) In another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, or triazinyl, the substituents of the aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in part of the ring are 1 to 4 groups independently selected from the group consisting of a halogen atom; a hydroxyl group; an oxo group; an alkyl group; a haloalkyl group; an alkoxyalkyl group; an alkoxy group; an alkylene group which may be substituted with 1 to 2 groups independently selected from a halogen atom; a cycloalkyl group; an alkanoyl group which may be substituted with 1 to 2 groups independently selected from the group consisting of a cycloalkyl group, an aryl group, and an alkoxy group; and an alkoxycarbonyl group which may be substituted with an aryl group; the aliphatic heterocyclic moiety of the aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in part of the ring is azolidinyl, diazolidinyl, azinanyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, diazepanyl, or thiazepanyl; the aryl group in the selected group in the substituent of the group represented by ring B is phenyl; Ring C is an optionally substituted phenyl group, an optionally substituted and partially hydrogenated monocyclic heteroaryl group, an optionally substituted monocyclic cycloalkyl group, or an optionally substituted monocyclic aliphatic heterocyclic group, and is an optionally substituted phenyl group; an optionally substituted and partially hydrogenated monocyclic heteroaryl group; an optionally substituted monocyclic cycloalkyl group; or an optionally substituted monocyclic aliphatic heterocyclic group, represented by Ring C;each of the substituents is a halogen atom; a hydroxyl group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group; an alkylene group; an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of a cycloalkyl group or an alkyl group optionally substituted with an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group;and alkanoyl groups, the heteroaryl moiety of the optionally substituted and optionally partially hydrogenated monocyclic heteroaryl group represented by ring C is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl or triazinyl, the aliphatic heterocyclic moiety of the optionally substituted monocyclic aliphatic heterocyclic group represented by ring C is azetidinyl, oxetanyl, oxolanyl, azolidinyl, thiolanyl, oxazolidinyl, diazolidinyl, thiazolidinyl, oxanyl, azinanyl, dioxanyl, oxazinanyl, diazinanyl, thiazinanyl, thianyl, oxepanyl, azepanyl, thiepanyl, oxazepanyl, diazepanyl, or thiazepanyl, and in each of the substituents of the group represented by ring C, the aryl group selected is phenyl, In each of the substituents of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is azetidinyl, oxetanyl, oxolanyl, azolidinyl, thiolanyl, oxazolidinyl, diazolidinyl, thiazolidinyl, oxanyl, adzinanyl, dioxanyl, oxazinanyl, diazinanyl, thiazinanyl, thianyl, oxepanyl, azepanyl, thiepanyl, oxazepanyl, diazepanyl, or thiazepanyl, or a ring in which two such aliphatic heterocyclic rings are fused or bonded via a spiro atom, or a pharmacologically acceptable salt thereof, is exemplified.

[0045] (7) In another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is thienyl or pyridyl, the substituents of the aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in part of the ring are 1 to 4 groups independently selected from the group consisting of a halogen atom; a hydroxyl group; an oxo group; an alkyl group; a haloalkyl group; an alkoxyalkyl group; an alkoxy group; an alkylene group which may be substituted with 1 to 2 groups independently selected from a halogen atom; a cycloalkyl group; an alkanoyl group which may be substituted with 1 to 2 groups independently selected from the group consisting of a cycloalkyl group, an aryl group, and an alkoxy group; and an alkoxycarbonyl group which may be substituted with an aryl group; the aliphatic heterocyclic moiety of the aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in part of the ring is azolidinyl, diazolidinyl, azinanyl, oxazinanyl, diazinanyl, azepanyl, oxazepanyl, diazepanyl, or thiazepanyl; the aryl group in the selected group in the substituent of the group represented by ring B is phenyl; Ring C is an optionally substituted phenyl group, an optionally substituted and partially hydrogenated monocyclic heteroaryl group, an optionally substituted monocyclic cycloalkyl group, or an optionally substituted monocyclic aliphatic heterocyclic group, and each of the substituents of the optionally substituted phenyl group, optionally substituted and partially hydrogenated monocyclic heteroaryl group, optionally substituted monocyclic cycloalkyl group, or optionally substituted monocyclic aliphatic heterocyclic group represented by Ring C is a halogen atom, a hydroxyl group, an oxo group, a cyano group, an alkyl group, a haloalkyl group, an alkoxy group, a cycloalkoxy group optionally substituted with a cyano group, a haloalkoxy group, an alkylene group,an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkanoyl group; Examples of the compound or a pharmacologically acceptable salt thereof according to any one of the above aspects (2) to (5) include: the aliphatic heterocyclic moiety of the optionally substituted monocyclic aliphatic heterocyclic group represented by ring C is azolidinyl or oxazinanyl, the aryl group in the selected group in each of the substituents of the group represented by ring C is phenyl, and the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group in each of the substituents of the group represented by ring C is azolidinyl, azinanyl, oxazinanyl, diazinanyl, azepanyl, oxazepanyl, or a ring in which two such aliphatic heterocycles are fused or bonded via a spiro atom;

[0046] (8) One preferred embodiment is a compound according to any one of the above embodiments (2) to (7), wherein, in the group represented by the above formula [II], ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C is an optionally substituted phenyl group, an optionally substituted 6-membered monocyclic heteroaryl group which may be partially substituted, or an optionally substituted 6-membered monocyclic aliphatic heterocyclic group, or a pharmaceutically acceptable salt thereof.

[0047] (9) In addition, as another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A are 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, the substituents of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in part of the ring are 1 to 4 groups independently selected from the group consisting of halogen atoms; oxo groups; alkyl groups; alkoxyalkyl groups; alkylene groups; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, phenyl groups and alkoxy groups; and alkoxycarbonyl groups which may be substituted with an aryl group; the 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in part of the ring is a 7-membered monocyclic aliphatic heterocyclic ring in which the aliphatic heterocyclic moiety contains 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; ring C is an optionally substituted phenyl group, an optionally substituted and partially hydrogenated 6-membered monocyclic heteroaryl group or an optionally substituted 6-membered monocyclic aliphatic heterocyclic group; Each of the substituents of the optionally substituted phenyl group, the optionally substituted and partially hydrogenated 6-membered monocyclic heteroaryl group, or the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring C is a halogen atom; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group;and 1 to 2 groups independently selected from the group consisting of an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; a cycloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkanoyl group, Examples of the compound or a pharmacologically acceptable salt thereof according to aspect (8) include: the compound in which the heteroaryl moiety of the optionally substituted and partially hydrogenated 6-membered monocyclic heteroaryl group represented by ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, and the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring C is a 6-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur;

[0048] (10) In addition, as another embodiment, in the group represented by the formula [II], the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is thienyl or pyridyl, the aliphatic heterocyclic moiety of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may contain a double bond in part of the ring is azepanyl, oxazepanyl, diazepanyl, or thiazepanyl, the aryl moiety of the aryl group in the substituent of the group represented by ring B is phenyl, the heteroaryl moiety of the 6-membered monocyclic heteroaryl group represented by ring C which may be substituted and which may be partially hydrogenated is pyridyl, pyrazinyl, or pyrimidinyl, the aliphatic heterocyclic moiety of the 6-membered monocyclic aliphatic heterocyclic group represented by ring C is oxazinanyl, and in each of the substituents of the group represented by ring C, the aryl group in the selected group is phenyl, In each of the substituents of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is azolidinyl, azinanyl, oxazinanyl, diazinanyl, azepanyl, or oxazepanyl, or a pharmaceutically acceptable salt thereof.

[0049] (11) Another preferred embodiment is a compound according to any one of the above embodiments (2) to (7), or a pharmacologically acceptable salt thereof, in which, in the group represented by the above formula [II], ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C is an optionally substituted 5-membered monocyclic heteroaryl group or an optionally substituted 5-membered monocyclic aliphatic heterocyclic group.

[0050] (12) In addition, as another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group, a substituent of the optionally substituted phenyl group represented by ring A is a halogen atom, ring B is a 7-membered monocyclic aliphatic heterocyclic group which may be substituted and which may have a double bond in a part of the ring, the substituent of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring is 1 to 4 groups independently selected from the group consisting of an oxo group; an alkyl group; and an alkylene group which may be substituted with 1 to 2 groups independently selected from a halogen atom, and the aliphatic heterocyclic moiety of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring is a 7-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, ring C is an optionally substituted 5-membered monocyclic heteroaryl group or an optionally substituted 5-membered monocyclic aliphatic heterocyclic group, each of the substituents of the optionally substituted 5-membered monocyclic heteroaryl group or the optionally substituted 5-membered monocyclic aliphatic heterocyclic group represented by ring C is 1 to 2 groups independently selected from the group consisting of a halogen atom; an alkyl group; a haloalkyl group; an alkylene group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; and an aryl group, each of the aryl groups in the selected group is phenyl, and the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is a 5-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, The compound according to aspect (11), wherein the aliphatic heterocyclic moiety of the optionally substituted 5-membered monocyclic aliphatic heterocyclic group represented by ring C is a 5-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmacologically acceptable salt thereof.

[0051] (13) As another embodiment, the compound or a pharmacologically acceptable salt thereof according to embodiment (11) or (12) above, wherein, in the group represented by formula [II], the aliphatic heterocyclic moiety of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may contain a double bond in part of the ring, is azepanyl, oxazepanyl, or diazepanyl; the heteroaryl moiety of the 5-membered monocyclic heteroaryl group represented by ring C, which may be substituted, is imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, or triazolyl; the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group represented by ring C, which may be substituted, is azolidinyl; and the aryl group in the selected group in each of the substituents of the group represented by ring C is phenyl.

[0052] (14) Another preferred embodiment is a compound according to any one of the above embodiments (2) to (7), or a pharmacologically acceptable salt thereof, wherein, in the group represented by the above formula [II], ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group.

[0053] (15) In another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group, a substituent of the optionally substituted phenyl group represented by ring A is a halogen atom, ring B is a 6-membered monocyclic aliphatic heterocyclic group which may be substituted and which may have a double bond in a part of the ring, the substituent of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B is 1 to 3 groups independently selected from the group consisting of an oxo group; an alkyl group; and a haloalkyl group, the aliphatic heterocyclic moiety of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring is a 6-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group, and each of the substituents of the optionally substituted phenyl group or the optionally substituted 6-membered monocyclic heteroaryl group represented by Ring C is a group independently selected from the group consisting of a halogen atom and a haloalkyl group, and the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by Ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmaceutically acceptable salt thereof.

[0054] (16) As another embodiment, the compound or a pharmacologically acceptable salt thereof according to the embodiment (14) or (15) is mentioned, wherein, in the group represented by formula [II], the aliphatic heterocyclic moiety of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may contain a double bond in part of the ring, is azinanyl, oxazinanyl, or diazinanyl, and the heteroaryl moiety of the 6-membered monocyclic heteroaryl group represented by ring C, which may be substituted, is pyridyl.

[0055] (17) Another preferred embodiment is a compound according to any one of the above embodiments (2) to (7), or a pharmacologically acceptable salt thereof, wherein, in the group represented by the above formula [II], ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C is an optionally substituted 5-membered monocyclic heteroaryl group.

[0056] (18) In another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group, a substituent of the optionally substituted phenyl group represented by ring A is a halogen atom, ring B is a 6-membered monocyclic aliphatic heterocyclic group which may be substituted and which may have a double bond in a part of the ring, the substituent of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring is 1 to 2 groups independently selected from the group consisting of an oxo group and an alkyl group, the aliphatic heterocyclic moiety of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring is a 6-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, ring C is an optionally substituted 5-membered monocyclic heteroaryl group, and the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by Ring C is a 5-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmaceutically acceptable salt thereof.

[0057] (19) As another embodiment, the compound or a pharmacologically acceptable salt thereof according to the embodiment (17) or (18) is exemplified, wherein, in the group represented by formula [II], the aliphatic heterocyclic moiety of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may contain a double bond in part of the ring, is diazinanyl, and the heteroaryl moiety of the 5-membered monocyclic heteroaryl group represented by ring C, which may be substituted, is pyrrolyl, imidazolyl, pyrazolyl, or triazolyl.

[0058] (20) As another preferred embodiment, the compound or a pharmaceutically acceptable salt thereof according to any one of the above embodiments (2) to (7), wherein, in the group represented by the above formula [II], ring B is an optionally substituted 5-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group.

[0059] (21) In another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group, the substituents of the optionally substituted phenyl group represented by ring A are 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, and an alkoxy group, ring B is a 5-membered monocyclic aliphatic heterocyclic group which may be substituted and which may have a double bond in a part of the ring, the substituents of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring are 1 to 3 groups independently selected from the group consisting of a hydroxyl group; an oxo group; an alkyl group; and an alkylene group, and the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring is a 5-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, and a pharmaceutically acceptable salt thereof. Examples of the compound according to aspect (20) include the compound or a pharmaceutically acceptable salt thereof according to aspect (20), wherein ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is a group independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, and an alkoxy group, and the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur.

[0060] (22) In addition, as another embodiment, the compound according to the above embodiment (20) or (21), or a pharmacologically acceptable salt thereof, may be mentioned, wherein, in the group represented by formula [II], the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may contain a double bond in part of the ring, is azolidinyl or diazolidinyl, and the heteroaryl moiety of the 6-membered monocyclic heteroaryl group represented by ring C, which may be substituted, is pyridyl.

[0061] (23) Another preferred embodiment is a compound according to any one of the above embodiments (2) to (7), or a pharmacologically acceptable salt thereof, wherein, in the group represented by the above formula [II], ring B is an optionally substituted 5-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C is an optionally substituted 5-membered monocyclic heteroaryl group.

[0062] (24) In another embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group, a substituent of the optionally substituted phenyl group represented by ring A is a halogen atom, ring B is a 5-membered monocyclic aliphatic heterocyclic group which may be substituted and which may have a double bond in a part of the ring, a substituent of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B is 1 to 2 groups independently selected from the group consisting of an oxo group and an alkyl group, an aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B which may be substituted and which may have a double bond in a part of the ring is a 5-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, ring C is an optionally substituted 5-membered monocyclic heteroaryl group, a substituent of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is an alkyl group, The compound or a pharmaceutically acceptable salt thereof according to aspect (23) above, wherein the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is a 5-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, is also included.

[0063] (25) In addition, as another embodiment, the compound according to the above embodiment (23) or (24), or a pharmacologically acceptable salt thereof, is mentioned, wherein, in the group represented by the above formula [II], the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may contain a double bond in part of the ring, is azolidinyl, and the heteroaryl moiety of the 5-membered monocyclic heteroaryl group represented by ring C, which may be substituted, is thiazolyl.

[0064] (26) Another preferred embodiment is a compound according to any one of the above embodiments (2) to (25), or a pharmacologically acceptable salt thereof, wherein, in the group represented by formula [II], ring A is a phenyl group optionally substituted with a halogen atom.

[0065] (27) In another preferred embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, the substituents of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, are 1 to 4 groups independently selected from the group consisting of halogen atoms; hydroxyl groups; oxo groups; alkyl groups; haloalkyl groups; alkoxyalkyl groups; alkoxy groups; alkylene groups which may be substituted with 1 to 2 groups independently selected from halogen atoms; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, aryl groups, and alkoxy groups; and alkoxycarbonyl groups which may be substituted with an aryl group; the aliphatic heterocyclic moiety of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B, which may have a double bond in part of the ring, is a 7-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl moiety of the aryl group in the substituent of the group represented by ring B is phenyl; Ring C is an optionally substituted phenyl group, an optionally substituted and partially hydrogenated 6-membered monocyclic heteroaryl group, or an optionally substituted 6-membered monocyclic aliphatic heterocyclic group, and each of the substituents of the optionally substituted phenyl group, the optionally substituted and partially hydrogenated 6-membered monocyclic heteroaryl group, or the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by Ring C is a halogen atom, a hydroxyl group, an oxo group, a cyano group, an alkyl group, a haloalkyl group, an alkoxy group,a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group; an alkylene group; an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkanoyl group; Examples of the compound according to aspect (2) include the compound or a pharmacologically acceptable salt thereof, wherein the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring C is a 6-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aryl moiety of the aryl group in each of the substituents of the group represented by ring C is phenyl, and the aliphatic heterocyclic moiety of the aliphatic heterocyclic group in each of the substituents of the group represented by ring C is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur;

[0066] (28) In another preferred embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, the substituents of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, are 1 to 4 groups independently selected from the group consisting of halogen atoms; hydroxyl groups; oxo groups; alkyl groups; haloalkyl groups; alkoxyalkyl groups; alkoxy groups; alkylene groups which may be substituted with 1 to 2 groups independently selected from halogen atoms; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, aryl groups, and alkoxy groups; and alkoxycarbonyl groups; the aliphatic heterocyclic moiety of the 7-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, is a 7-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl moiety of the aryl group in the substituent of the group represented by ring B is phenyl; ring C is an optionally substituted 5-membered monocyclic heteroaryl group or an optionally substituted 5-membered monocyclic aliphatic heterocyclic group, and each of the substituents of the optionally substituted 5-membered monocyclic heteroaryl group or the optionally substituted 5-membered monocyclic aliphatic heterocyclic group represented by ring C is a halogen atom, a hydroxyl group, an oxo group, a cyano group, an alkyl group, a haloalkyl group, an alkoxy group, a cycloalkoxy group optionally substituted with a cyano group, a haloalkoxy group, an alkylene group,and 1 to 4 groups independently selected from the group consisting of an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; and an alkanoyl group, Examples of the compound according to aspect (2) include the compound or a pharmacologically acceptable salt thereof, wherein the aliphatic heterocyclic moiety of the optionally substituted 5-membered monocyclic aliphatic heterocyclic group represented by ring C is a 6-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aryl group in the selected group in each of the substituents of the group represented by ring C is phenyl, and the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group in each of the substituents of the group represented by ring C is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur;

[0067] (29) In addition, as another preferred embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, the substituents of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, are 1 to 4 groups independently selected from the group consisting of halogen atoms; hydroxyl groups; oxo groups; alkyl groups; haloalkyl groups; alkoxyalkyl groups; alkoxy groups; alkylene groups which may be substituted with 1 to 2 groups independently selected from halogen atoms; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, aryl groups, and alkoxy groups; and alkoxycarbonyl groups; the aliphatic heterocyclic moiety of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, is a 6-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl group selected in the substituents of the group represented by ring B is phenyl; ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group; Each of the substituents of the optionally substituted phenyl group or the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is a halogen atom; a hydroxyl group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group; an alkylene group;and 1 to 4 groups independently selected from the group consisting of an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; and an alkanoyl group; the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by Ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, and in each of the substituents of the group represented by Ring C, the aryl group in the selected group is phenyl, In each of the substituents of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmaceutically acceptable salt thereof, as described in aspect (2);

[0068] (30) In another preferred embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A are 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, the substituents of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, are 1 to 4 groups independently selected from the group consisting of halogen atoms; hydroxyl groups; oxo groups; alkyl groups; haloalkyl groups; alkoxyalkyl groups; alkoxy groups; alkylene groups which may be substituted with 1 to 2 groups independently selected from halogen atoms; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, aryl groups, and alkoxy groups; and alkoxycarbonyl groups; the aliphatic heterocyclic moiety of the 6-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, is a 6-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl group selected in the substituents of the group represented by ring B is phenyl; ring C is an optionally substituted 5-membered monocyclic heteroaryl group; The substituent of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is a halogen atom; a hydroxyl group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group; an alkylene group;and 1 to 4 groups independently selected from the group consisting of an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; and an alkanoyl group; the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by Ring C is a 5-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; and the aryl group in the selected group, in the substituent of the group represented by Ring C, is phenyl. In the substituent of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmaceutically acceptable salt thereof.

[0069] (31) In another preferred embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring B is an optionally substituted 5-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, the substituents of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, are 1 to 4 groups independently selected from the group consisting of halogen atoms; hydroxyl groups; oxo groups; alkyl groups; haloalkyl groups; alkoxyalkyl groups; alkoxy groups; alkylene groups which may be substituted with 1 to 2 groups independently selected from halogen atoms; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, aryl groups, and alkoxy groups; and alkoxycarbonyl groups; the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, is a 5-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl group selected in the substituents of the group represented by ring B is phenyl; ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group; The substituent of the optionally substituted phenyl group or the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is preferably a halogen atom, a hydroxyl group, an oxo group, a cyano group, an alkyl group, a haloalkyl group, an alkoxy group, a cycloalkoxy group optionally substituted with a cyano group, a haloalkoxy group, an alkylene group,and 1 to 4 groups independently selected from the group consisting of an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; and an alkanoyl group; the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by Ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, and in each of the substituents of the group represented by Ring C, the aryl group in the selected group is phenyl, In each of the substituents of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmaceutically acceptable salt thereof, as described in aspect (2);

[0070] (32) In another preferred embodiment, in the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring B is an optionally substituted 5-membered monocyclic aliphatic heterocyclic group which may contain a double bond in part of the ring, the substituents of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, are 1 to 4 groups independently selected from the group consisting of halogen atoms; hydroxyl groups; oxo groups; alkyl groups; haloalkyl groups; alkoxyalkyl groups; alkoxy groups; alkylene groups which may be substituted with 1 to 2 groups independently selected from halogen atoms; cycloalkyl groups; alkanoyl groups which may be substituted with 1 to 2 groups independently selected from the group consisting of cycloalkyl groups, aryl groups, and alkoxy groups; and alkoxycarbonyl groups; the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group represented by ring B, which may be substituted and which may have a double bond in part of the ring, is a 5-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl group selected in the substituents of the group represented by ring B is phenyl; ring C is an optionally substituted 5-membered monocyclic heteroaryl; The substituent of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is a halogen atom; a hydroxyl group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group; an alkylene group;and 1 to 4 groups independently selected from the group consisting of an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; and an alkanoyl group; the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by Ring C is a 5-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; and the aryl group in the selected group, in the substituent of the group represented by Ring C, is phenyl. In the substituent of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmaceutically acceptable salt thereof.

[0071] (33) In addition, other preferred embodiments include (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one; (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-7-(trifluoromethyl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; 3-Dihydropyrido[3,2-f][1,4]oxazepin-5-one; (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; (6R)-2-(1-fluorocyclopropyl)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-thiazolo[5,4-c]azepin-4-one; (7R)-2-[(1S*,5R*)-3-azabicyclo[3.1.0]hexan-3-yl]-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f]oxazepin-5-one; (6R)-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2,6-dimethyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one; (6R)-2-(1,1-difluoroethyl)-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one;(6R)-2-cyclopropyl-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one; (6R)-2-(1-fluorocyclopropyl)-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one; (6R)-2-cyclopropyl-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one; (6R)-2-(1-fluorocyclopropyl)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one; (6R)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-2-(trifluoromethyl)-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one; (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3,8-dimethyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one; (3R)-8-cyclopropyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one; (3R)-8-cyclopropyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; (7R)-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2,7-dimethyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one;(7R)-2-Cyclopropyl-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one; (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one; and (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydro-1H-pyrido[2,3-f][1,4]diazepin-5-one or a pharmacologically acceptable salt thereof.

[0072] (34) In another embodiment, the compound of the formula [I] is a compound of the following formula [III]: [wherein ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group; and ring D represents an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring], or a pharmaceutically acceptable salt thereof.

[0073] (35) In another embodiment, in the group represented by formula [III], each of the substituents of the optionally substituted aryl group, the optionally substituted heteroaryl group, and the optionally substituted aliphatic heterocyclic group represented by ring A is 1 to 3 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, an alkoxyalkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkanoyl group, an alkoxycarbonyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, a sulfonyl group optionally substituted with an alkyl group, an aminocarbonyl group optionally substituted with 1 to 2 alkyl groups, a nitro group, and an aryl group, the aryl moiety of the optionally substituted aryl group represented by ring A is a 6- to 10-membered monocyclic or bicyclic aryl, and the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring A is a 5-10 membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, the substituents of the optionally substituted aliphatic heterocyclic group represented by ring D which may contain a double bond in a part of the ring are 1 to 8 groups independently selected from the group consisting of an oxo group; an optionally substituted alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; an aliphatic heterocyclic group; an alkoxy group; a cycloalkoxy group; an alkylthio group; an amino group; an alkoxycarbonyl group; an alkanoyl group; an alkylsulfonyl group; a halogen atom; a hydroxyl group; and a cyano group, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring D which may contain a double bond in a part of the ring is a 5-7 membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, The compound according to the above embodiment (34) or a pharmacologically acceptable salt thereof is exemplified.

[0074] (36) In another embodiment, in the group represented by the formula [III], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the substituents of the optionally substituted aliphatic heterocyclic group represented by ring D and which may contain a double bond in part of the ring are 1 to 8 groups independently selected from the group consisting of an oxo group, an optionally substituted alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aliphatic heterocyclic group, an alkoxy group, a cycloalkoxy group, an alkylthio group, an amino group, an alkoxycarbonyl group, an alkanoyl group, an alkylsulfonyl group, a halogen atom, a hydroxyl group, and a cyano group, and in each of the substituents of the group represented by ring D, the substituents of the optionally substituted alkyl group in the selected group are 1 to 5 groups independently selected from the group consisting of an oxo group, a cycloalkyl group which may be substituted with a haloalkyl group or a halogen atom, an aryl group which may be substituted with an alkyl group or a halogen atom, a heteroaryl group which may be substituted with an alkyl group, a heterocyclic group which may be substituted with an oxo group, a halogen atom, a hydroxyl group, a cyano group, an alkoxy group, a cycloalkoxy group, a haloalkoxy group, an amino group, an alkylamino group, a dialkylamino group, a cycloalkylamino group, and an alkylthio group, The aliphatic heterocyclic moiety of the aliphatic heterocyclic group represented by ring D, which may be substituted and may contain a double bond in part of the ring, is a 5- to 7-membered monocyclic aliphatic heterocycle containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a pharmacologically acceptable salt thereof.

[0075] (37) In another embodiment, in the group represented by the formula [III], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, or triazinyl, the substituents of the optionally substituted aliphatic heterocyclic group represented by ring D and which may contain a double bond in part of the ring are 1 to 8 groups independently selected from the group consisting of an oxo group, an optionally substituted alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aliphatic heterocyclic group, an alkoxy group, a cycloalkoxy group, an alkylthio group, an amino group, an alkoxycarbonyl group, an alkanoyl group, an alkylsulfonyl group, a halogen atom, a hydroxyl group, and a cyano group, and in each of the substituents of the group represented by ring D, the substituent of the optionally substituted alkyl group selected is an oxo group, a haloalkyl group, or a cycloalkyl group which may be substituted with a halogen atom, an aryl group which may be substituted with an alkyl group or a halogen atom, a heteroaryl group which may be substituted with an alkyl group, an aliphatic heterocyclic group which may be substituted with an oxo group, a halogen atom, a hydroxyl group, a cyano group, an alkoxy group, a cycloalkoxy group, a haloalkoxy group, an amino group, an alkylamino group, a dialkylamino group;and 1 to 5 groups independently selected from the group consisting of cycloalkylamino groups and alkylthio groups, and the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring D and optionally containing a double bond in part of the ring is azolidinyl, diazolidinyl, adinaninyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, diazepanyl, or thiazepanyl, as described in aspect (34), or a pharmacologically acceptable salt thereof.

[0076] (38) In one embodiment, in the group represented by the formula [III], ring A is an optionally substituted phenyl group, a substituent of the optionally substituted phenyl group represented by ring A is a halogen atom, a substituent of the optionally substituted aliphatic heterocyclic group represented by ring D which may contain a double bond in part of the ring is 1 to 3 groups independently selected from the group consisting of an oxo group; an optionally substituted alkyl group; an aryl group; a heteroaryl group; an aliphatic heterocyclic group, and an alkylsulfonyl group, and in each of the substituents of the group represented by ring D, a substituent of the optionally substituted alkyl group in the selected group is independently selected from the group consisting of an oxo group; a cycloalkyl group which may be substituted with a halogen atom; an aryl group; a heteroaryl group; a halogen atom, and an alkoxy group, The aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring D and optionally containing a double bond in part of the ring is azolidinyl, diazolidinyl, azinanyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, or diazepanyl, or a pharmaceutically acceptable salt thereof, is exemplified.

[0077] (39) In another embodiment, the compound of the formula [I] is represented by the following formula [IV]: [wherein, ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group; R １represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted amino group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group; and Ring E represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring.

[0078] (40) In another embodiment, in the group represented by formula [IV], each of the substituents of the optionally substituted aryl group, the optionally substituted heteroaryl group, and the optionally substituted aliphatic heterocyclic group represented by ring A is 1 to 3 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, an alkoxyalkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkanoyl group, an alkoxycarbonyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, a sulfonyl group optionally substituted with an alkyl group, an aminocarbonyl group optionally substituted with 1 to 2 alkyl groups, a nitro group, and an aryl group, the aryl moiety of the optionally substituted aryl group represented by ring A is a 6- to 10-membered monocyclic or bicyclic aryl, and the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring A is a 5- to 10-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, １is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group or an optionally substituted alkynyl group, R １ a substituent of the optionally substituted alkyl group, the optionally substituted alkenyl group, and the optionally substituted alkynyl group in the group represented by R １ the substituents of the optionally substituted cycloalkyl group and the optionally substituted cycloalkenyl group in the group represented by the formula (I) are alkyl groups, alkenyl groups, or alkynyl groups; the aryl moiety of the optionally substituted aryl group represented by ring E is a 6- to 10-membered monocyclic or bicyclic aryl; the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring E is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring E which may contain a double bond in part of the ring is a 5- to 10-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; The substituents of the optionally substituted aryl group, the optionally substituted heteroaryl group, and the optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, represented by ring E, are 1 to 3 groups independently selected from the group consisting of an alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; a halogen atom; a haloalkyl group; a hydroxyl group; a cyano group; an alkoxy group; a cycloalkoxy group; an aryloxy group; a haloalkoxy group; an amino group; an alkylamino group; a dialkylamino group; a cycloalkylamino group, and an alkylthio group, or a pharmaceutically acceptable salt thereof.

[0079] (41) In another embodiment, in the group represented by the formula [IV], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a nitro group, and an aryl group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, and R １ is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group or an optionally substituted alkynyl group, R １ a substituent of the optionally substituted alkyl group, the optionally substituted alkenyl group, and the optionally substituted alkynyl group in the group represented by R １the substituents of the optionally substituted cycloalkyl group and the optionally substituted cycloalkenyl group in the group represented by the formula (I) are alkyl groups, alkenyl groups, or alkynyl groups, ring E is an optionally substituted aryl group or an optionally substituted heteroaryl group, the aryl moiety of the optionally substituted aryl group represented by ring E is a 6- to 10-membered monocyclic or bicyclic aryl, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring E is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the substituents of the optionally substituted aryl group and the optionally substituted heteroaryl group represented by ring E are 1 to 3 groups independently selected from the group consisting of alkyl groups; cycloalkyl groups; aryl groups; heteroaryl groups; halogen atoms; haloalkyl groups; hydroxyl groups; cyano groups; alkoxy groups; cycloalkoxy groups; aryloxy groups; haloalkoxy groups; amino groups; alkylamino groups; dialkylamino groups; cycloalkylamino groups, and alkylthio groups. Examples thereof include the compound described in (39) above or a pharmacologically acceptable salt thereof.

[0080] (42) In another embodiment, in the group represented by the formula [IV], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a nitro group, and an aryl group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, or triazinyl, and R １is an alkyl group, ring E is an optionally substituted aryl group or an optionally substituted heteroaryl group, the aryl moiety of the optionally substituted aryl group represented by ring E is phenyl or naphthyl, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring E is pyridyl, azaindolyl, imidazopyridyl or benzimidazolyl, and substituents of the optionally substituted aryl group and the optionally substituted heteroaryl group in ring E are independently selected from the group consisting of alkyl groups, cycloalkyl groups, aryl groups, heteroaryl groups, halogen atoms, haloalkyl groups, hydroxyl groups, cyano groups, alkoxy groups, cycloalkoxy groups, aryloxy groups, haloalkoxy groups, amino groups, alkylamino groups, dialkylamino groups, cycloalkylamino groups and alkylthio groups.

[0081] (43) In another embodiment, in the group represented by the formula [IV], ring A is an optionally substituted phenyl group or an optionally substituted thienyl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted thienyl group represented by ring A is 1 to 2 groups independently selected from the group consisting of an aryl group, a halogen atom, an alkyl group, or an alkoxy group, and R １ is a propyl group, ring E is an optionally substituted phenyl group or an optionally substituted heteroaryl group, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring E is pyridyl, azaindolyl, imidazopyridyl or benzimidazolyl, and substituents of the optionally substituted phenyl group and the optionally substituted heteroaryl in ring E are groups independently selected from the group consisting of alkyl groups, dialkylamino groups, cycloalkylamino groups and alkoxy groups.

[0082] (44) Another preferred embodiment is a pharmaceutical composition containing, as an active ingredient, the compound according to any one of the above embodiments (1) to (43) or a pharmacologically acceptable salt thereof.

[0083] (45) Another embodiment includes the pharmaceutical composition according to embodiment (44), which is used for the prevention or treatment of various diseases and / or symptoms associated therewith that can be improved by increasing central TRH concentration, or for improving the prognosis of such diseases and / or symptoms associated therewith.

[0084] (46) In another embodiment, the pharmaceutical composition according to the above embodiment (44) is a TRH-DE inhibitor.

[0085] (47) In another embodiment, the pharmaceutical composition according to the above embodiment (45) or (46) is an agent for preventing or treating spinocerebellar degeneration, chronic pain, sleep disorders, or other psychiatric or neurological disorders and / or symptoms associated therewith.

[0086] (48) In another embodiment, the pharmaceutical composition according to the above embodiment (47) is used, wherein the chronic pain is neuropathic pain or nociceptive pain.

[0087] (49) In addition, other embodiments include the pharmaceutical composition according to embodiment (48), wherein the neuropathic pain is pain associated with diabetic neuropathy, postherpetic neuralgia, pain associated with chemotherapy-induced peripheral neuropathy, trigeminal neuralgia, complex regional pain syndrome, post-stroke pain, spinal cord injury pain, neuralgia, or pain associated with nerve injury.

[0088] (50) In another embodiment, the pharmaceutical composition according to the above embodiment (48) is used, wherein the nociceptive pain is pain associated with rheumatoid arthritis, pain associated with osteoarthritis, postoperative pain, or myofascial pain.

[0089] (51) In another embodiment, the pharmaceutical composition according to the above embodiment (47) is used, wherein the sleep disorder is hypersomnia, circadian rhythm disorder, sleep-disordered breathing, or other sleep disorders.

[0090] (52) In another embodiment, the pharmaceutical composition according to the above embodiment (51) is used, wherein the hypersomnia is narcolepsy, idiopathic hypersomnia, or recurrent hypersomnia.

[0091] (53) In another embodiment, the pharmaceutical composition according to the above embodiment (51) is used, wherein the circadian rhythm disorder is shift work sleep disorder, delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, or irregular sleep-wake pattern.

[0092] (54) In another embodiment, the pharmaceutical composition according to the above embodiment (51) is used, wherein the sleep-disordered breathing is sleep apnea syndrome.

[0093] (55) In another embodiment, the pharmaceutical composition according to the above embodiment (51) is used, wherein the other sleep disorder is jet lag syndrome, asynchrony syndrome, restless legs syndrome, periodic limb movement disorder, hypersomnia or REM sleep behavior disorder associated with insomnia associated with neurological or psychiatric disorders.

[0094] (56) In addition, as another embodiment, the pharmaceutical composition according to the above embodiment (47) may be used, wherein the other psychiatric / neurological disease and / or its accompanying symptoms are spinal muscular atrophy, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, chronic fatigue syndrome, vascular dementia, bipolar disorder, depression, spinal cord injury, cerebral infarction, head trauma, chronic disturbance of consciousness, speech disorder, easy fatigability, functional disorder caused by nerve damage, or functional disorder caused by surgery.

[0095] (57) Another preferred embodiment is a method for treating various diseases and / or symptoms associated therewith that can be improved by increasing the central TRH concentration, which comprises administering to a patient a therapeutically effective amount of a compound according to any one of the above embodiments (1) to (43) or a pharmacologically acceptable salt thereof.

[0096] (58) In another embodiment, the method of treatment according to the above embodiment (57) is used, wherein the various diseases and / or symptoms associated therewith that can be improved by increasing the central TRH concentration are spinocerebellar degeneration, pain, sleep disorders, or other psychiatric / neurodegenerative diseases and / or symptoms associated therewith.

[0097] When the compound [I], [II], [III] or [IV] of the present invention has an asymmetric carbon atom in the molecule, it may exist as a plurality of stereoisomers (i.e., diastereoisomers, optical isomers) based on the asymmetric carbon atom, and the present invention includes any one of these stereoisomers and mixtures thereof.

[0098] The compound [I], [II], [III] or [IV] of the present invention may contain an isotope (e.g., ３ H. １３ C. １４ C. １５ N. １８ F. ３２ P. ３５ S. １２５ I, etc.), and deuterium-labeled compounds.

[0099] Compound [I], [II], [III], or [IV] of the present invention, or a pharmacologically acceptable salt thereof, has TRH-DE inhibitory activity and is therefore useful for preventing or treating various diseases and / or associated symptoms that can be improved by increasing central TRH levels, or for improving the prognosis of these diseases. Examples of such diseases include spinocerebellar degeneration, chronic pain, sleep disorders, and other nervous system diseases and / or associated symptoms, with chronic pain and sleep disorders being particularly preferred. Examples of spinocerebellar degeneration include hereditary spinocerebellar degeneration and sporadic (non-hereditary) spinocerebellar degeneration. Examples of hereditary spinocerebellar degeneration include autosomal recessive diseases and / or associated symptoms, and autosomal dominant diseases and / or associated symptoms. Examples of autosomal recessive genetic diseases and / or associated symptoms include Friedreich's ataxia, isolated vitamin E deficiency ataxia, aprataxin deficiency, senataxin deficiency, and Charlevoix-Saguet spastic ataxia. Examples of autosomal dominant genetic diseases and / or associated symptoms include spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2), spinocerebellar ataxia type 3 (SCA3), spinocerebellar ataxia type 6 (SCA6), spinocerebellar ataxia type 31 (SCA31), and dentatorubral-pallidoluysian atrophy. Examples of sporadic (non-genetic) spinocerebellar degeneration include pure cerebellar ataxia-type spinocerebellar degeneration and multisystem spinocerebellar degeneration. Examples of pure cerebellar ataxia-type spinocerebellar degeneration include cortical cerebellar atrophy. Examples of multisystem spinocerebellar degeneration include multiple system atrophy. Examples of multisystem atrophy include olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager syndrome. Examples of chronic pain include neuropathic pain, nociceptive pain, and mixed pain. Examples of neuropathic pain include pain associated with diabetic neuropathy, postherpetic neuralgia, pain associated with chemotherapy-induced peripheral neuropathy, trigeminal neuralgia, complex regional pain syndrome, post-stroke pain, spinal cord injury pain, neuralgia, and pain associated with nerve injury.Nociceptive pain includes, for example, pain associated with rheumatoid arthritis, pain associated with osteoarthritis, postoperative pain, or myofascial pain. Mixed pain includes, for example, cancer pain, fibromyalgia syndrome, chronic low back pain, or phantom limb pain. Sleep disorders include, for example, hypersomnia, circadian rhythm disorders, sleep-disordered breathing, and hypersomnia associated with other sleep disorders. Hypersomnia includes, for example, narcolepsy, idiopathic hypersomnia, or recurrent hypersomnia. Circadian rhythm disorders include, for example, shift work-related sleep disorder, delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, or irregular sleep-wake pattern. Sleep-disordered breathing includes, for example, sleep apnea syndrome. Other sleep disorders include, for example, jet lag syndrome, asynchrony syndrome, restless legs syndrome, periodic limb movement disorder, and hypersomnia or REM sleep behavior disorder associated with insomnia associated with neurological or psychiatric disorders. Other nervous system diseases and / or their associated symptoms include, for example, the following:Hereditary ataxias (such as congenital cerebellar ataxia and Machado-Joseph disease), spinal muscular atrophy and related syndromes (such as spinal muscular atrophy, spinal-bulbar muscular atrophy, amyotrophic lateral sclerosis, cervical spondylotic muscular atrophy), extrapyramidal disorders and abnormal movements (such as Parkinson's disease and Parkinsonism), other degenerative diseases of the nervous system (such as Alzheimer's disease and progressive leukoencephalopathy), episodic and paroxysmal disorders (such as epilepsy, migraine, cluster headache syndrome), cerebral palsy and other paralytic syndromes (such as cerebral palsy, hemiplegia, paraplegia and quadriplegia), chronic fatigue syndrome, organic mental disorders including symptomatic (such as Alzheimer's disease, vascular dementia, delirium), mental and behavioral disorders due to psychoactive substance use (such as alcohol-induced behavioral disorders and drug-induced behavioral disorders), schizophrenia, schizophreniform disorders and delusional disorders, Mood disorders (such as bipolar disorder, depression, persistent mood disorder), Eating disorders (such as anorexia nervosa, bulimia nervosa), Neurotic disorders, stress-related disorders and somatoform disorders (such as phobic anxiety disorder, obsessive-compulsive disorder, somatoform disorder), Disorders of psychological development (such as autism spectrum disorder), Behavioral and emotional disorders typically of onset in childhood and adolescence (such as hyperactivity disorder, tic disorder), Obesity, Adrenoleukodystrophy, Spinal cord injury, Cerebral infarction, Head trauma, Delayed onset of consciousness, Symptoms and signs related to cognition, perception, emotional state and behavior (such as irritability, restlessness and agitation, lethargy and blunted affect), Speech disorders, Easy fatigability, Functional impairment due to nerve damage, Functional impairment due to surgery, etc.

[0100] As described above, compound [I], [II], [III], or [IV] of the present invention, or a pharmacologically acceptable salt thereof, has excellent inhibitory activity against TRH-DE. The inhibitory activity against TRH-DE can be confirmed according to the assay method in the Experimental Example "2. TRH-DE Inhibition Test" described below. Furthermore, compound [I], [II], [III], or [IV] of the present invention, or a pharmacologically acceptable salt thereof, also exhibited efficacy in a central nervous system activating test (evaluated using a SCANET apparatus according to the method described in Japanese Patent No. 4817281) using mechanical hyperalgesia (Randall-Selit method) and spontaneous locomotion as indicators in chronic constriction injury (CCI) model rats (prepared according to the method described in Pain 1988; 33:87-107.), a neuropathic pain model.

[0101] Compound [I], [II], [III] or [IV] of the present invention can be used for pharmaceutical purposes either in the free form or in the form of a pharmacologically acceptable salt, such as an inorganic acid salt such as hydrochloride, sulfate, phosphate or hydrobromide, or an organic acid salt such as acetate, fumarate, oxalate, citrate, methanesulfonate, benzenesulfonate, tosylate or maleate.

[0102] The compound [I], [II], [III] or [IV] of the present invention or a pharmacologically acceptable salt thereof includes any of its internal salts, adducts, solvates or hydrates thereof, etc.

[0103] Compound [I], [II], [III], or [IV] of the present invention, or a pharmacologically acceptable salt thereof, can be administered orally or parenterally either alone or as a pharmaceutical composition containing the compound and a pharmacologically acceptable carrier. The pharmacologically acceptable carrier may be any carrier commonly used in the art, such as diluents, binders (syrup, gum arabic, gelatin, sorbitol, tragacanth, polyvinylpyrrolidone, etc.), excipients (lactose, sucrose, corn starch, potassium phosphate, sorbitol, glycine, etc.), lubricants (magnesium stearate, talc, polyethylene glycol, silica, etc.), disintegrants (potato starch), and wetting agents (sodium lauryl sulfate, etc.). The dosage form of such pharmaceutical compositions is not particularly limited, and includes, for example, conventional pharmaceutical formulations such as tablets, granules, capsules, powders, injections, inhalants, and suppositories.

[0104] The dosage of compound [I], [II], [III] or [IV] or a pharmacologically acceptable salt thereof of the present invention varies depending on the administration method, the age, weight, condition, etc. of the patient, but in the case of parenteral administration, it is usually 0.001 mg / kg to 100 mg / kg, preferably 0.03 mg / kg to 30 mg / kg per day. In the case of oral administration, it is usually 0.001 mg / kg to 100 mg / kg, preferably 0.03 mg / kg to 30 mg / kg per day.

[0105] The compound of the present invention or a pharmacologically acceptable salt thereof can be prepared, for example, as follows: Synthetic Method A1 [In the formula, W １ represents a hydroxyl group or an amino group which may be protected by a protecting group, X represents a leaving group such as a halogen atom, ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group, ring B represents an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, and ring C represents an optionally substituted and partially hydrogenated aryl group, an optionally substituted and partially hydrogenated heteroaryl group, an optionally substituted cycloalkyl group, or an optionally substituted aliphatic heterocyclic group.

[0106] Among the target compounds [I] of the present invention, the compound represented by general formula [Ia] can be prepared, for example, as follows. First, a compound represented by general formula [a] is subjected to a reductive amination reaction with a compound represented by general formula [b] to obtain a compound represented by general formula [c]. The compound represented by general formula [c] is amidated with a compound represented by general formula [d] to obtain a compound represented by general formula [e], which is then subjected to an intramolecular SnAr reaction to produce the target compound [Ia]. The reductive amination reaction of compound [a] with compound [b] or a salt thereof can be carried out in a suitable solvent, for example, in the presence of a reducing agent and an acid or a Lewis acid, according to a conventional method. Any solvent that does not interfere with the reaction may be used, and examples thereof include halogenated aliphatic hydrocarbons such as methylene chloride, alcohols such as methanol, ethers such as tetrahydrofuran, aromatic hydrocarbons such as toluene, and mixtures thereof. Examples of reducing agents include sodium triacetoxyborohydride, sodium borohydride, hydrogen, and palladium catalysts (e.g., palladium catalysts supported on activated carbon). Examples of acids include acetic acid. Examples of Lewis acids include titanium(IV) chloride and tetraisopropyl titanate. The amount of compound [b] used can be 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to compound [a]. The amount of reducing agent used can be 1 to 10 equivalents, preferably 1 to 3 equivalents, relative to compound [a]. The amount of acid or Lewis acid used can be 1 to 10 equivalents, preferably 1 to 3 equivalents, relative to compound [a]. This reaction can be carried out at -10°C to 100°C, preferably 10°C to 50°C.

[0107] The reaction of compound [c] with compound [d] can be carried out in a suitable solvent in the presence or absence of a base according to a conventional method. Any solvent that does not interfere with the reaction can be used, including, for example, ethers such as tetrahydrofuran, amides such as N,N-dimethylformamide, acetonitrile, or a mixture thereof. Examples of bases include triethylamine, diisopropylethylamine, and diazabicycloundecene. The amount of compound [c] used can be 1.0 to 10.0 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [d]. This reaction can be carried out at temperatures between −78°C and room temperature, preferably between 0°C and room temperature. The intramolecular SnAr reaction of compound [e] can be carried out in a suitable solvent in the presence of a base according to a conventional method. Any solvent that does not interfere with the reaction can be used, including, for example, ethers such as tetrahydrofuran, amides such as N,N-dimethylformamide, acetonitrile, water, or a mixture thereof. Examples of the base include alkali metal hydrides such as sodium hydride, alkali metal alkoxides such as sodium tert-butoxide, organic amines such as diisopropylethylamine, and sodium hydroxide. The amount of base used can be 1.0 to 10.0 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [e]. This reaction can be carried out at temperatures between -78°C and room temperature, preferably between 0°C and room temperature. In the reaction of compound [c] and compound [d], the resulting compound [e] can be subsequently subjected to an intramolecular SnAr reaction in the same reaction system to obtain compound [Ia]. In addition, in the reaction of compound [c] and compound [d], an excess amount of compound [d] can be used to obtain W １ or an amino group which may be protected by a protecting group, represented by the following formula (I), followed by hydrolysis, to obtain compound [e].

[0108] Synthesis method A2 [In the formula, the symbols have the same meanings as defined above.]

[0109] Among the target compounds [I] of the present invention, the compound represented by general formula [Ia] can be prepared, for example, as follows. Compound [i] is obtained using compound [f] in the same manner as in Synthesis Method A1, and then deprotection is performed to obtain compound [j]. The target compound [Ia] can be prepared by reacting compound [j] or a salt thereof with a sulfonic acid anhydride or a sulfonyl chloride. The reductive amination reaction of compound [f] with compound [b] or a salt thereof can be carried out in the same manner as in the reaction of compound [a] with compound [b] in Synthesis Method A1. The reaction of compound [g] with compound [d] can be carried out in the same manner as in the reaction of compound [c] with compound [d] in Synthesis Method A1. The reaction from compound [h] to compound [i] can be carried out in the same manner as in the reaction from compound [e] to compound [Ia] in Synthesis Method A1. The deprotection reaction of compound [i] can be carried out in a suitable solvent in the presence of an acid or Lewis acid according to a conventional method. Any solvent may be used as long as it does not interfere with the reaction, and examples thereof include ethers such as 1,4-dioxane and tetrahydrofuran, halogenated aliphatic hydrocarbons such as chloroform, aromatic hydrocarbons such as toluene, acetonitrile, or a mixture thereof. Examples of acids include hydrochloric acid, sulfuric acid, and trifluoroacetic acid. Examples of Lewis acids include triethylsilyl trifluoromethanesulfonate. The amount of acid or Lewis acid used can be 1.0 to 10.0 equivalents, preferably 1.0 to 2.0 equivalents, relative to compound [i]. This reaction can be carried out at temperatures from -78°C to room temperature, preferably 0°C to room temperature. The reaction of compound [j] or a salt thereof with a sulfonic acid anhydride or sulfonyl chloride can be carried out in a suitable solvent in the presence or absence of a base according to a conventional method. The solvent may be any solvent that does not interfere with the reaction, and examples thereof include ethers such as tetrahydrofuran, amides such as dimethylformamide, or mixtures thereof. The base may be an amine such as triethylamine. The amount of sulfonic acid anhydride or sulfonyl chloride used may be 1.0 to 10.0 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [j] or a salt thereof.The amount of the base used may be 1.0 to 10.0 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [j]. This reaction may be carried out at a temperature of −78° C. to room temperature, preferably 0° C. to room temperature.

[0110] Synthesis method B [In the formula, R １ represents a hydrogen atom or an alkyl group, and other symbols have the same meanings as defined above.

[0111] Among the target compounds [I] of the present invention, compounds represented by general formula [Ib], [Ic], or [Id] can be prepared, for example, as follows. Compound [a] and compound [m] are subjected to a reductive amination reaction to obtain compound [n]. Compound [p] obtained by the reaction of this compound [n] with compound [o] is subjected to a ring-closing metathesis reaction to produce target compound [Ib]. Furthermore, target compound [Ic] can be prepared by reducing the obtained compound [Ib], and target compound [Id] can also be prepared by cyclopropylating compound [Ib]. The reaction of compound [a] and compound [m] can be carried out in the same manner as the reaction of compound [a] and compound [b] in Synthesis Method A1. The reaction of compound [n] and compound [o] can be carried out in a suitable solvent, for example, in the presence of a condensing agent and a base, according to a conventional method. Any solvent may be used as long as it does not interfere with the reaction. Examples of the solvent include amides such as dimethylformamide, ethers such as tetrahydrofuran, halogenated aliphatic hydrocarbons such as chloroform, aromatic hydrocarbons such as toluene, acetonitrile, and mixtures thereof. Condensing agents include o-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. Bases include amines such as diisopropylethylamine. The amount of the condensing agent used can be 1.0 to 5.0 equivalents, preferably 1.2 to 3.0 equivalents, relative to compound [n]. The amount of the base used can be 0 to 10 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [n]. The reaction can be carried out at 0°C to 100°C, preferably at room temperature. The ring-closing metathesis reaction of compound [p] can be carried out in the presence of a catalyst in a suitable solvent according to a conventional method. The solvent may be any solvent that does not interfere with the reaction, such as ethers such as tetrahydrofuran, halogenated aliphatic hydrocarbons such as chloroform, aromatic hydrocarbons such as toluene, acetonitrile, or a mixture thereof.Examples of the catalyst include Grubbs catalyst (first generation, second generation) and Hoveyda-Grubbs catalyst (first generation, second generation). The amount of the catalyst used can be 0.01 to 5.0 equivalents, preferably 0.1 to 1.0 equivalents, relative to compound [p]. This reaction can be carried out at 0 to 100°C, preferably at room temperature. The reduction reaction of compound [Ib] can be carried out according to a conventional method in a suitable solvent in the presence of a catalyst under a hydrogen atmosphere. The solvent may be any solvent that does not interfere with the reaction, and examples include alcohols such as methanol, esters such as ethyl acetate, ethers such as tetrahydrofuran, and mixtures thereof. Examples of the catalyst include palladium / carbon catalysts. The amount of the catalyst used can be 0.3 to 1.0, preferably 0.3, by weight, relative to compound [Ib]. This reaction can be carried out at 0°C to room temperature, preferably at room temperature. The reaction from Compound [Ib] to Compound [Id] can be carried out according to a conventional method in a suitable solvent in the presence of (trifluoromethyl)trimethylsilane and sodium iodide. Examples of the solvent include ethers such as tetrahydrofuran. The amount of (trifluoromethyl)trimethylsilane used can be 1 to 10 equivalents, preferably 3 to 5 equivalents, relative to Compound [Ib]. The amount of sodium iodide used can be 0.1 to 5 equivalents, preferably 0.3 to 1.0 equivalent, relative to Compound [Ib]. This reaction can be carried out at room temperature to 150°C, preferably 50°C to 80°C.

[0112] Synthesis method C [In the formula, R ２ represents a protecting group such as an alkyl group, and other symbols have the same meanings as above.

[0113] Among the target compounds [I] of the present invention, the compound represented by general formula [Ie] can be prepared, for example, as follows: Compound [a] and compound [q] or a salt thereof are subjected to a reductive amination reaction to obtain compound [r]. Compound [r] is hydrolyzed to obtain compound [s] or a salt thereof, and then the target compound [Ie] can be prepared by an intramolecular condensation reaction. The reductive amination reaction between compound [a] and compound [q] or a salt thereof can be carried out in the same manner as in the reaction between compound [a] and compound [b] in Synthesis Method A1. Hydrolysis of compound [r] can be carried out in a suitable solvent in the presence of a base and water according to a conventional method. Any solvent that does not interfere with the reaction can be used, and examples of the solvent include alcohols such as ethanol and ethers such as tetrahydrofuran. Examples of the base include alkali metal hydroxides such as sodium hydroxide. The reaction can be carried out at a temperature between 0°C and room temperature, preferably at room temperature. The amount of base used can be 1.0 to 10.0 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [r]. The intramolecular condensation reaction of compound [s] or a salt thereof can be carried out in a suitable solvent, for example, in the presence of a condensing agent and a base, according to a conventional method. Any solvent that does not interfere with the reaction can be used, and examples thereof include amides such as dimethylformamide, ethers such as tetrahydrofuran, halogenated aliphatic hydrocarbons such as chloroform, aromatic hydrocarbons such as toluene, acetonitrile, and mixtures thereof. Examples of condensing agents include o-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. Examples of bases include amines such as diisopropylethylamine. The amount of the condensing agent used may be 1.0 to 5.0 equivalents, preferably 1.2 to 3.0 equivalents, relative to compound [s]. This reaction may be carried out at a temperature of 0°C to 100°C, preferably at room temperature.

[0114] Synthesis method D [In the formula, L represents a leaving group such as 4-methylbenzenesulfonate, benzenesulfonate, etc., and the other symbols have the same meanings as above.]

[0115] Among the target compounds [I] of the present invention, the compound represented by the general formula [If] can be prepared, for example, by the nucleophilic substitution reaction between compound [t] and compound [u]. The nucleophilic substitution reaction between compound [t] and compound [u] can be carried out in a suitable solvent, for example, in the presence of a base, according to a conventional method. Any solvent that does not interfere with the reaction can be used, including, for example, amides such as dimethylformamide, ethers such as tetrahydrofuran, halogenated aliphatic hydrocarbons such as chloroform, aromatic hydrocarbons such as toluene, acetonitrile, and mixtures thereof. Examples of the base include alkali metal hydrides such as sodium hydride and potassium carbonate. The amount of compound [u] used can be 1.0 to 5.0 equivalents, preferably 1.2 to 3.0 equivalents, relative to compound [t]. The reaction can be carried out at 0°C to 200°C, preferably 100°C to 150°C.

[0116] Synthesis method E [wherein P represents a protecting group such as a tert-butoxycarbonyl group or a benzyloxycarbonyl group, and R ３ represents an alkyl group, and R ４ represents an alkyl group, and R ５ represents an alkyl group, and the other symbols have the same meanings as above.]

[0117] Among the target compounds [I] of the present invention, the compound represented by general formula [Ig] can be produced, for example, as follows. Compound [x] is obtained by deprotection accompanied by an intramolecular cyclization reaction of compound [w] obtained by condensation reaction of compound [c] of synthetic method A1 with compound [c-1] and compound [v]. Compound [x] is thioamidated to obtain compound [y], which can then be reacted with hydrazine derivative [z] or a salt thereof to produce target compound [Ig]. The reaction of compound [c-1] with compound [v] can be carried out in the same manner as the reaction of compound [c] with compound [d] in synthetic method A1. Deprotection accompanied by an intramolecular cyclization reaction of compound [w] can be carried out in the same manner as the cyclization reaction of compound [e] in synthetic method A1. Compound [y] can be produced by reacting compound [x] in a solvent, in the presence of a sulfurizing agent, and in the presence of a base. An example of the sulfurizing agent is Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide). An example of the base is an amine such as triethylamine, N,N-diisopropylethylamine, or pyridine. Any solvent that does not affect the reaction may be used, and examples include aromatic hydrocarbons such as toluene and xylene; and ethers such as tetrahydrofuran, 1,4-dioxane, and 1,2-dimethoxyethane. The amount of the sulfurizing agent used in this reaction is 0.4 to 2.0 equivalents, preferably 0.5 to 0.7 equivalents, relative to compound [x]. The amount of the base used is 1.0 to 20 equivalents, preferably 2.0 to 7.0 equivalents, relative to compound [x]. This reaction can be carried out at 50°C to 180°C, preferably 80°C to 130°C. The reaction of compound [y] with compound [z] or a salt thereof can be carried out, for example, in a suitable solvent in the presence or absence of a base. Examples of salts of compound [z] that can be used include salts with inorganic acids such as hydrochloride and sulfate. Any solvent that does not interfere with the reaction can be used, and examples include amides such as N-methylpyrrolidone, ethers such as tetrahydrofuran, alcohols such as methanol, dimethyl sulfoxide, water, and mixtures thereof.A base may be added to promote the reaction. Examples of such bases include diisopropylethylamine, diazabicycloundecene, sodium carbonate, etc., with diisopropylethylamine being preferred. The amount of compound [z] or a salt thereof used may be 1.0 to 10 equivalents, preferably 2.0 to 7.0 equivalents, relative to compound [y]. This reaction may be carried out at room temperature to 250°C, preferably 120°C to 180°C.

[0118] Synthesis method F [In the formula, the symbols have the same meanings as defined above.]

[0119] Among the target compounds [I] of the present invention, the compound represented by general formula [Ih] can be prepared, for example, as follows. Compound [n] and compound [d] are amidated to obtain compound [aa]. Compound [aa] is cyclized by an intramolecular coupling reaction to obtain compound [ab], which is then reduced to produce target compound [Ih]. First, the amidation of compound [n] and compound [d] can be carried out in the same manner as in the reaction of compound [c] and compound [d] in synthesis method A1. The cyclization of compound [aa] by an intramolecular coupling reaction can be carried out in a suitable solvent in the presence of a base, a phosphonium ligand, and a palladium catalyst, with or without water, according to a conventional method. Any solvent that does not interfere with the reaction may be used, and examples thereof include ethers such as dioxane, amides such as dimethylformamide, aromatic hydrocarbons such as toluene, and mixtures thereof. Examples of phosphonium ligands include bromotris(pyrrolidino)phosphonium hexafluorophosphate (PyBROP) and benzotriazol-1-yloxy-trisdimethylaminophosphonium (BOP). Examples of bases include amines such as triethylamine, alkali metal carbonates such as sodium carbonate, and potassium phosphate. Examples of palladium catalysts include bis(triphenylphosphine)palladium dichloride, tetrakis(triphenylphosphine)dipalladium, palladium acetate, and 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride. The amount of the phosphonium condensing agent used can be 1.0 to 2.0 equivalents, preferably 1.2 to 1.5 equivalents, relative to Compound [aa]. The amount of the base used can be 2.0 to 6.0 equivalents, preferably 3.0 to 4.0 equivalents, relative to Compound [aa]. The amount of the palladium catalyst used may be 0.01 to 1.0 equivalent, preferably 0.1 to 0.5 equivalent, relative to compound [aa]. This reaction may be carried out at room temperature to 150°C, preferably 80°C to 120°C. The reduction reaction of compound [ab] may be carried out in the same manner as in the preparation of compound [Id] by synthetic method B.

[0120] Synthesis method G [In the formula, the symbols have the same meanings as defined above.]

[0121] Among the target compounds [I] of the present invention, the compound represented by general formula [Ii] can be prepared, for example, as follows. Among the compounds represented by general formula [c] in Synthesis Method A1, the compound represented by general formula [c-2] is subjected to an amidation reaction with compound [ac] to obtain compound [e-2], which is then subjected to cyclization via an intramolecular Mitsunobu reaction to produce target compound [Ii]. The amidation reaction between compound [c-2] and compound [ac] can be carried out in the same manner as in the reaction between compound [c] and compound [d] in Synthesis Method A1. The cyclization of compound [e-2] via an intramolecular Mitsunobu reaction can be carried out in a suitable solvent in the presence of an azodicarboxylic acid derivative and a phosphine derivative, according to a conventional method. Any solvent may be used as long as it does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane, aromatic hydrocarbons such as toluene, nitriles such as acetonitrile, and mixtures thereof. Examples of azodicarboxylic acid derivatives include azodicarboxylic acid dialkyl esters such as diethyl azodicarboxylate and diisopropyl azodicarboxylate; and azodicarboxamides such as N,N,N',N'-tetramethylazodicarboxamide. Examples of phosphine derivatives include triarylphosphines such as triphenylphosphine and trialkylphosphines such as tributylphosphine. The amount of the azodicarboxylic acid derivative used can be 1.0 to 5.0 equivalents, preferably 2.0 to 3.0 equivalents, relative to compound [e-2]. The amount of the phosphine derivative used can be 1.0 to 5.0 equivalents, preferably 2.0 to 3.0 equivalents, in molar ratio relative to compound [e-2]. This reaction can be carried out at 0°C to 120°C, preferably room temperature to 80°C.

[0122] Synthesis method H1 [In the formula, R ６ represents a protecting group such as an alkyl group, and other symbols have the same meanings as above.

[0123] Among the target compounds [I] of the present invention, compounds represented by general formula [Ij] or [Ik] can be prepared, for example, as follows. Compound [ag] can be obtained by coupling a compound [af] obtained by an amidation reaction between compound [ad] and compound [c-2]. The target compound [Ij] can be prepared by a cyclization reaction of compound [ag]. Furthermore, the target compound [Ik] can also be prepared by dehydrating the target compound [Ij]. First, the amidation reaction between compound [ad] and compound [c-2] can be carried out in the same manner as in the reaction between compound [n] and compound [o] in synthesis method B. Next, the coupling reaction of compound [af] can be carried out in a suitable solvent in the presence of a base, a phosphonium ligand, a palladium catalyst, and an organotin compound according to conventional methods. Any solvent that does not interfere with the reaction may be used, and examples thereof include ethers such as dioxane, amides such as dimethylformamide, aromatic hydrocarbons such as toluene, and mixtures thereof. Examples of bases include alkali metal carbonates such as sodium carbonate, potassium phosphate, and cesium fluoride. Examples of phosphonium ligands include bromotris(pyrrolidino)phosphonium hexafluorophosphate (PyBROP) and benzotriazol-1-yloxy-trisdimethylaminophosphonium (BOP). Examples of palladium catalysts include bis(triphenylphosphine)palladium dichloride, tetrakis(triphenylphosphine)dipalladium, palladium acetate, and 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride. Examples of organotin compounds include (1-ethoxyethenyl)tributylstannane. The amount of the phosphonium condensing agent used can be 1.0 to 2.0 equivalents, preferably 1.2 to 1.5 equivalents, relative to compound [af]. The base can be used in an amount of 2.0 to 6.0 equivalents, preferably 3.0 to 4.0 equivalents, relative to compound [af]. The palladium catalyst can be used in an amount of 0.01 to 1.0 equivalents, preferably 0.1 to 0.5 equivalents, relative to compound [af].The amount of the organotin compound used can be 1.0 to 5.0 equivalents, preferably 1.2 to 2.5 equivalents, relative to compound [af]. This reaction can be carried out at room temperature to 150°C, preferably 80°C to 120°C. The cyclization reaction of compound [ag] can be carried out by treating with an acid in a suitable solvent. Any solvent that does not interfere with the reaction can be used, for example, esters such as ethyl acetate, halogenated aliphatic hydrocarbons such as chloroform, alcohols such as methanol, or mixtures thereof. Examples of acids include hydrochloric acid and trifluoroacetic acid. The dehydration reaction of target compound [Ij] can be carried out in a suitable solvent in the presence of a reducing agent and a Lewis acid according to conventional methods. Any solvent that does not interfere with the reaction can be used, for example, ethers such as tetrahydrofuran, halogenated aliphatic hydrocarbons such as chloroform, aromatic hydrocarbons such as toluene, acetonitrile, or mixtures thereof. An example of the reducing agent is triethylsilane. An example of the Lewis acid is boron trifluoride-ethyl ether complex. The amount of the reducing agent used can be 1.0 to 15.0 equivalents, preferably 1.2 to 7.0 equivalents, relative to compound [Ij]. The amount of the reducing agent used can be 1.0 to 10.0 equivalents, preferably 1.2 to 5.0 equivalents, relative to compound [Ij]. This reaction can be carried out at -100°C to room temperature, preferably -50°C to 0°C.

[0124] Synthesis method H2 [In the formula, R ７ represents an alkyl group, and the other symbols have the same meanings as above.]

[0125] Among the target compounds [I] of the present invention, compounds represented by general formula [Ij] or [Ik] can be prepared, for example, as follows. Compound [ak] or a salt thereof can be obtained by deprotecting compound [aj] obtained by the reaction of compound [ah] with compound [ai]. Compound [an] can be obtained by sulfonamidating compound [ak] or a salt thereof. Target compound [Ij] can be prepared by a nucleophilic addition reaction with compound [an]. Furthermore, target compound [Ik] can also be prepared by a dehydration reaction with target compound [Ij], similar to the synthetic method H1. First, the reaction of compound [ah] with compound [ai] can be carried out according to a conventional method in a suitable solvent in the presence or absence of a base, by removing the generated water from the reaction system using a Dean-Stark or similar method. Any solvent may be used as long as it does not interfere with the reaction, and examples thereof include ethers such as tetrahydrofuran, amides such as N,N-dimethylformamide, aromatic hydrocarbons such as toluene, and acetonitrile. Examples of bases include amines such as triethylamine. The amount of compound [ai] used may be 1.0 to 5.0 equivalents, preferably 1.1 to 1.5 equivalents, relative to compound [ah]. The amount of base used may be 0 to 5.0 equivalents, preferably 0.2 to 1.5 equivalents, relative to compound [ah]. This reaction may be carried out at room temperature to 180°C, preferably 110°C to 150°C. Next, deprotection of compound [aj] may be carried out in the same manner as in the reaction from compound [i] to compound [j] in Synthesis Method A2. The sulfonamidation reaction of compound [ak] may be carried out in the same manner as in the reaction from compound [j] to compound [Ia] in Synthesis Method A2. The nucleophilic addition reaction of compound [an] can be carried out in the presence of a Grignard reagent (organomagnesium halide) in a suitable solvent according to a conventional method. The solvent may be any solvent that does not interfere with the reaction, and examples thereof include ethers such as tetrahydrofuran, aromatic hydrocarbons such as toluene, aliphatic hydrocarbons such as hexane, or mixtures thereof.The amount of Grignard reagent used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, relative to compound [an]. This reaction can be carried out at -78°C to room temperature, preferably 0°C to room temperature.

[0126] Synthesis method I [In the formula, R ８ represents an alkyl group such as a methyl group, and other symbols have the same meanings as above.

[0127] Among the target compounds [I] of the present invention, the compound represented by general formula [II] can be prepared, for example, as follows. Compound [Aq] or a salt thereof can be obtained by deprotecting compound [AP] obtained by the reaction of compound [Ah] with compound [AO]. Compound [Aq] or a salt thereof can be sulfonamidated to prepare target compound [II]. First, the reaction of compound [Ah] with compound [AO] can be carried out in a suitable solvent according to a conventional method. Any solvent that does not interfere with the reaction can be used, and examples of the solvent include amides such as N-methylpyrrolidone, ethers such as tetrahydrofuran, alcohols such as methanol, dimethyl sulfoxide, and mixtures thereof. The amount of compound [AO] used can be 0.2 to 5.0 equivalents, preferably 0.3 to 2.0 equivalents, relative to compound [Ah]. This reaction can be carried out at room temperature to 180°C, preferably room temperature to 130°C. Next, deprotection of compound [ap] can be carried out in the same manner as in the reaction from compound [i] to compound [j] in the above-mentioned Synthesis Method A2. The sulfonamidation reaction of compound [aq] can be carried out in the same manner as in the reaction from compound [j] to compound [Ia] in the above-mentioned Synthesis Method A2.

[0128] Synthesis method J [In the formula, R ９ represents an alkyl group such as a methyl group, and other symbols have the same meanings as above.

[0129] Among the target compounds [I] of the present invention, the compound represented by the general formula [Im] can be produced, for example, as follows. Compound [as] or a salt thereof can be obtained by deprotecting compound [ar]. Compound [as] or a salt thereof can be sulfonamidated to produce target compound [Im]. First, deprotection of compound [ar] can be carried out in the same manner as in the reaction from compound [i] to compound [j] in the above-mentioned Synthesis Method A2. Next, sulfonamidation reaction of compound [as] can be carried out in the same manner as in the reaction from compound [j] to compound [Ia] in the above-mentioned Synthesis Method A2.

[0130] Synthesis method K [In the formula, R １０ represents an alkyl group such as a methyl group, and W ２ represents a hydroxyl group or an amino group, and other symbols have the same meanings as above.]

[0131] Among the target compounds [I] of the present invention, the compound represented by the general formula [In] can be prepared, for example, as follows. Compound [au] can be obtained by a reductive alkylation reaction between compound [ah] and compound [at]. Compound [au] can be obtained by amidating and cyclizing compound [ax]. The target compound [In] can be prepared by deprotecting this compound and sulfonamidating it. First, the reductive alkylation reaction between compound [ah] and compound [at] can be carried out in the same manner as in the reaction between compound [a] and compound [b] in Synthesis Method A1. Next, the amidation reaction between compound [au] and compound [av] can be carried out in the same manner as in the reaction between compound [c] and compound [d] in Synthesis Method A1. The cyclization reaction of compound [aw] can be carried out in a suitable solvent in the presence of a base according to a conventional method. Any solvent may be used as long as it does not interfere with the reaction, and examples thereof include ethers such as tetrahydrofuran, amides such as N,N-dimethylformamide, acetonitrile, water, or a mixture thereof. Examples of the base include alkali metal hydrides such as sodium hydride, alkali metal alkoxides such as sodium tert-butoxide, organic amines such as diisopropylethylamine, and alkali metal carbonates such as sodium hydroxide and sodium carbonate. The amount of base used may be 1.0 to 10.0 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [aw]. This reaction may be carried out at temperatures from -78°C to room temperature, preferably 0°C to room temperature. The deprotection reaction of compound [ax] may be carried out in the same manner as in the reaction from compound [i] to compound [j] in the aforementioned Synthesis Method A2. The sulfonamidation reaction of compound [ay] may be carried out in the same manner as in the reaction from compound [j] to compound [Ia] in the aforementioned Synthesis Method A2.

[0132] Synthesis method L [In the formula, R １１ represents an alkyl group such as a methyl group, and other symbols have the same meanings as above.]

[0133] Among the target compounds [I] of the present invention, the compound represented by the general formula [Io] can be prepared, for example, as follows. Compound [ba] can be obtained by reductive alkylation of compound [ah] with compound [az]. Compound [ba] is deprotected to obtain compound [bb], which is then intramolecularly cyclized to obtain compound [bc]. The target compound [Io] can be prepared by sulfonamidation of compound [bc]. First, the reductive alkylation of compound [ah] with compound [az] can be carried out in the same manner as in the reaction of compound [a] with compound [b] in Synthesis Method A1. Next, the deprotection of compound [ba] can be carried out in a suitable solvent in the presence of a Lewis acid according to conventional methods. Any solvent that does not interfere with the reaction may be used, including, for example, ethers such as 1,4-dioxane and tetrahydrofuran, halogenated aliphatic hydrocarbons such as chloroform, aromatic hydrocarbons such as toluene, acetonitrile, or a mixture thereof. Examples of Lewis acids include boron tribromide. The amount of Lewis acid used can be 1.0 to 10.0 equivalents, preferably 1.0 to 2.0 equivalents, relative to compound [ba]. This reaction can be carried out at temperatures from -100°C to room temperature, preferably from -78°C to room temperature. The intramolecular cyclization reaction of compound [bb] can be carried out in a conventional manner by reacting with carbonyldiimidazole in a suitable solvent (e.g., N,N-dimethylformamide) in the presence of a base (e.g., diisopropylethylamine). The sulfonamidation reaction of compound [bc] can be carried out in the same manner as the reaction from compound [j] to compound [Ia] in the above-mentioned Synthesis Method A2.

[0134] Synthesis method M [In the formula, P represents a protecting group such as a tert-butoxycarbonyl group, and the other symbols have the same meanings as defined above.]

[0135] Among the target compounds [I] of the present invention, the compound represented by the general formula [Ip] can be produced, for example, as follows. Compound [be] obtained by the amidation reaction of compound [ah] with compound [bd] is alkylated to obtain compound [bf], and then deprotected to obtain compound [bg] or a salt thereof. The target compound [Ip] can be produced by sulfonamidating compound [bg] or a salt thereof. First, the amidation reaction of compound [ah] with compound [bd] can be carried out in the same manner as the reaction of compound [n] with compound [o] in synthesis method B. Next, the alkylation reaction of compound [be] can be N-alkylated by reacting compound [be] with an alkylating agent. For example, N-alkylation can be achieved by reacting with methyl iodide, propyl iodide, or the like in a solvent (e.g., acetonitrile) in the presence of a base (e.g., sodium hydride, or the like). The deprotection reaction of compound [bf] can be carried out in the same manner as in the reaction from compound [i] to compound [j] in Synthesis Method A2. The reaction of compound [bg] or a salt thereof with a sulfonic acid anhydride or a sulfonyl chloride can be carried out in the same manner as in the reaction of compound [j] with a sulfonic acid anhydride or a sulfonyl chloride in Synthesis Method A2.

[0136] Synthesis method N [In the formula, Ns represents a nosyl group (2-nitrobenzenesulfonyl group), and the other symbols have the same meanings as defined above.]

[0137] Among the target compounds [I] of the present invention, the compound represented by the general formula [Iq] can be prepared, for example, as follows. Compound [bh] obtained by the reaction of compound [ah] with NsCl (2-nitrobenzenesulfonyl chloride) is subjected to N-alkylation to obtain compound [bi], which is then deprotected to obtain compound [bj] or a salt thereof. Compound [bk] can be obtained by sulfonamidating compound [bj] or a salt thereof. Compound [bk] can be obtained by deprotecting (denosylating) compound [bk] to obtain compound [bl] or a salt thereof. Compound [bl] or a salt thereof can be subjected to an amidation reaction with compound [bd] to prepare target compound [Iq]. First, the reaction of compound [ah] with NsCl can be carried out according to a conventional method in a suitable solvent (e.g., dichloromethane) in the presence of a base (e.g., triethylamine). Next, the N-alkylation reaction of compound [bh] can be carried out in the same manner as the reaction from compound [be] to compound [bf] in Synthesis Method M. The deprotection reaction of compound [bi] can be carried out in the same manner as the reaction from compound [i] to compound [j] in Synthesis Method A2. The reaction of compound [bj] or a salt thereof with sulfonic acid anhydride or sulfonyl chloride can be carried out in the same manner as the reaction from compound [j] to sulfonic acid anhydride or sulfonyl chloride in Synthesis Method A2. The deprotection (denosylation) reaction of compound [bk] can be carried out in a conventional manner by reacting with a thiol compound (e.g., mercaptoacetic acid) in a suitable solvent (e.g., N,N-dimethylformamide) in the presence of a base (e.g., lithium hydroxide). The amidation reaction of compound [bl] or a salt thereof can be carried out in the same manner as the reaction from compound [n] to compound [o] in Synthesis Method B.

[0138] Synthesis method O [In the formula, the symbols have the same meanings as defined above.]

[0139] Among the target compounds [I] of the present invention, the compounds represented by the general formula [Ir] can be produced by intramolecular cyclization of compound [c]. The intramolecular cyclization of compound [c] can be carried out in a conventional manner by reacting it with carbonyldiimidazole in a suitable solvent (e.g., N,N-dimethylformamide) in the presence of a base (e.g., diisopropylethylamine).

[0140] Synthesis method P [In the formula, the symbols have the same meanings as defined above.]

[0141] Among the target compounds [I] of the present invention, the compound represented by general formula [Is] can be produced, for example, by amidating compound [c] to obtain compound [bm] and then cyclizing the resulting compound. First, the amidation reaction of compound [c] with compound [av] can be carried out in the same manner as in the reaction of compound [au] with compound [av] in synthesis method K. As the solvent, in addition to the same solvents as above, halogenated aliphatic hydrocarbons such as chloroform and methylene chloride, or mixtures thereof, may be used. The cyclization reaction of compound [bm] can be carried out in the same manner as in the cyclization reaction of compound [aw] in synthesis method K.

[0142] Synthesis method Q [In the formula, the symbols have the same meanings as defined above.]

[0143] Among the target compounds [I] of the present invention, the compound represented by the general formula [It] can be produced by an intramolecular condensation reaction of compound [bn]. The intramolecular condensation reaction of compound [bn] can be carried out in the same manner as the intramolecular condensation reaction of compound [s] in Synthesis Method C.

[0144] Synthesis method R [In the formula, the symbols have the same meanings as defined above.]

[0145] Among the target compounds [I] of the present invention, the compound represented by the general formula [Iu] can be prepared, for example, as follows. Compound [bq] can be obtained by amidating compound [n] and subjecting compound [bp] to a ring-closing metathesis reaction. The target compound [Iu] can be prepared by reducing the resulting compound [bq]. First, the amidation reaction of compound [n] and compound [bo] can be carried out in the same manner as in the reaction of compound [au] and compound [av] in Synthesis Method K. In addition to the solvents mentioned above, halogenated aliphatic hydrocarbons such as chloroform and methylene chloride, or mixtures thereof, may also be used as the solvent. The ring-closing metathesis reaction of compound [bp] can be carried out in the same manner as in the ring-closing metathesis reaction of compound [p] in Synthesis Method B. The reduction reaction of compound [bq] can be carried out in the same manner as in the reduction reaction of compound [Ib] in Synthesis Method B.

[0146] Intermediate synthesis method a [In the formula, the symbols have the same meanings as above.] In synthesis method C, among the compounds represented by general formula [q], the compound represented by general formula [q-1] can be produced by deprotecting compound [C] obtained by the Mitsunobu reaction of compound [A] and compound [B]. The Mitsunobu reaction of compound [A] and compound [B] can be carried out in the presence of an azodicarboxylic acid derivative and a phosphine derivative. Any solvent that does not affect the reaction can be used, and examples of the solvent include ethers such as tetrahydrofuran and 1,4-dioxane, aromatic hydrocarbons such as toluene, nitriles such as acetonitrile, and mixtures thereof. Examples of azodicarboxylic acid derivatives include azodicarboxylic acid dialkyl esters such as diethyl azodicarboxylate and diisopropyl azodicarboxylate; and azodicarboxamides such as N,N,N',N'-tetramethylazodicarboxamide. Examples of phosphine derivatives include triarylphosphines such as triphenylphosphine and trialkylphosphines such as tributylphosphine. The amount of compound [B] used can be 1.0 to 15.0 equivalents, preferably 2.0 to 3.0 equivalents, relative to compound [A]. The amount of azodicarboxylic acid derivative used can be 1.0 to 15.0 equivalents, preferably 2.0 to 3.0 equivalents, relative to compound [A]. The amount of phosphine derivative used can be 1.0 to 15.0 equivalents, preferably 2.0 to 3.0 equivalents, relative to compound [A]. This reaction can be carried out at 0°C to 100°C, preferably at room temperature. Deprotection of compound [C] can be carried out in the same manner as in the reaction from compound [i] to compound [j] in the above-mentioned Synthesis Method A2.

[0147] Intermediate synthesis method b [In the formula, the symbols have the same meanings as above.] In synthesis method C, among the compounds represented by general formula [q], the compound represented by general formula [q-2] can be produced by deprotecting compound [F] obtained by the Mitsunobu reaction between compound [D] and compound [E] or the reductive amination reaction with compound [F]. The Mitsunobu reaction between compound [D] and compound [E] can be carried out in the same manner as the reaction between compound [A] and compound [B] in synthesis method a for the intermediate. The reductive amination reaction between compound [D] and compound [F] can be carried out in the same manner as the reaction between compound [a] and compound [b] in synthesis method A1. The deprotection of compound [F] can be carried out in the same manner as the reaction from compound [i] to compound [j] in synthesis method A2.

[0148] Intermediate synthesis method c [In the formula, R １２ represents a protecting group such as a methyl group, and other symbols have the same meaning as above.] In synthetic method J, the compound represented by general formula [ar] can be produced by deprotecting compound [J] obtained by reductive alkylation reaction of compound [ah] with compound [H], and subjecting the resulting compound [K] to a cyclization reaction. The reductive alkylation reaction of compound [ah] with compound [H] can be carried out in the same manner as in the reaction of compound [a] with compound [b] in synthetic method A1. The deprotection reaction of compound [J] can be carried out in the same manner as in the reaction from compound [r] to compound [s] in synthetic method C. The cyclization reaction of compound [K] can be carried out in the same manner as in the reaction from compound [s] to compound [Ie] in synthetic method C.

[0149] The starting compounds in the above-mentioned methods can be produced in the same manner as known methods and / or methods described in the Examples below. The introduction of protecting groups to functional groups and the removal of functional protecting groups can be carried out with reference to known methods (e.g., PROTECTIVE GROUPS in ORGANIC SYNTHESIS (Theodora W. Greene, Peter G.M.Wuts)). Furthermore, the compounds of the present invention and intermediate compounds produced by the above-mentioned methods can be further structurally converted into other target compounds or intermediates by methods described in the Examples below and / or known methods, or a combination thereof. Specifically, the following methods can be mentioned.

[0150] (1) Conversion of a Halogen Atom to an Alkyl Group A compound having a halogen atom can be converted to the corresponding alkyl group by coupling with, for example, an alkylboronic acid derivative or an organozinc reactant.

[0151] (2) Conversion of a halogen atom to an acyl group A compound having a halogen atom can be converted to the corresponding acyl group by carrying out the same reaction as that for converting compound [af] to compound [ag] in General Synthesis Method H1, followed by acid treatment.

[0152] (3) Conversion of a Halogen Atom to an Amino Group A compound having a halogen atom can be converted to the corresponding amino group by coupling with an amine derivative using a palladium catalyst and a ligand, for example.

[0153] (4) Conversion of a halogen atom to an alkoxy group or an amino group A compound having a halogen atom on an aryl group can be converted to the corresponding alkoxy group or amino group by reacting it with a nucleophilic compound, such as sodium methoxide or an amine.

[0154] (5) Conversion of a Carbonyl Group to a Dihalogenated Alkyl Group A carbonyl group can be converted to the corresponding dihalogenated alkyl group, for example, by reacting it with a halogenating agent. For example, a corresponding starting compound having a carbonyl group can be reacted with a halogenating agent (e.g., a fluorinating agent such as bis(2-methoxyethyl)aminosulfur trifluoride) in a solvent (e.g., dichloromethane, ethanol, etc.) to produce a compound having the corresponding dihalogenated alkyl group.

[0155] (6) Conversion of a hydroxy group to an alkoxy group A hydroxy group can be converted to the corresponding alkoxy group by reacting it with an alkylating agent. For example, a corresponding starting compound having a hydroxy group can be reacted with an alkylating agent (e.g., a methylating agent such as methyl iodide) in a solvent (e.g., dichloromethane) in the presence of a base (e.g., sodium hydride) to produce a compound having the corresponding alkoxy group.

[0156] (7) N-Alkylation A nitrogen-containing compound can be N-alkylated by reacting it with an alkylating agent. For example, N-alkylation can be achieved by reacting it with methyl iodide in a solvent (e.g., acetonitrile) in the presence of a base (e.g., potassium carbonate). Alternatively, N-alkylation can be achieved by reacting a nitrogen-containing compound with an aldehyde (e.g., formaldehyde) in a solvent (e.g., dichloromethane) in the presence of a base (e.g., N,N-diisopropylethylamine) and a reducing agent (e.g., sodium triacetoxyborohydride).

[0157] (8) N-Acylation A nitrogen-containing compound can be N-acylated by reacting it with an acylating agent. For example, N-acylation can be achieved by reacting it with an acylating agent (e.g., acetyl chloride) in a solvent (e.g., chloroform) in the presence of a base (e.g., N,N-diisopropylethylamine).

[0158] (9) Halogenation of Aromatic Derivatives A compound having an aromatic ring can be halogenated by reacting it with a halogenating agent, for example, by reacting it with a halogenating agent (e.g., N-bromosuccinimide) in a solvent (e.g., acetonitrile).

[0159] (10) Conversion of a Halogen Atom to a Nitrile Group A compound having a halogen atom can be converted to a nitrile group by reacting it with zinc cyanide in the presence of a palladium catalyst. For example, the conversion to a nitrile group can be achieved by reacting it with zinc cyanide in a solvent (e.g., N,N-dimethylformamide) in the presence of a palladium catalyst (e.g., tetrakistriphenylphosphine palladium).

[0160] (11) Conversion of Bromine to Iodine Aryl bromide compounds can be converted to iodine using copper iodide. For example, they can be converted to iodine by reacting them with copper iodide and sodium iodide in a solvent (e.g., 1,4-dioxane) in the presence of a ligand (e.g., trans-N,N'-dimethylcyclohexane-1,2-amine).

[0161] (12) Conversion of Iodine to Trifluoromethyl Group An aryl iodide compound can be converted to a trifluoromethyl group by reacting it with a trifluoromethylating agent. For example, the compound can be converted to the corresponding trifluoromethyl group by reacting it with a trifluoromethylating agent (e.g., methyl difluoro(fluorosulfonyl)acetate) in the presence of copper iodide in a solvent (e.g., N,N-dimethylformamide).

[0162] (13) Difluoromethylation by C—H Activation A difluoromethylated compound can be produced by reacting a compound having an aromatic group capable of C—H activation with a difluoromethylation reagent. For example, the compound can be converted to the corresponding difluoromethyl group by reacting with a difluoromethylation reagent (e.g., difluoromethanesulfinic acid) in a solvent (e.g., dimethyl sulfoxide) in the presence of tert-butyl hydroperoxide.

[0163] As used herein, THF means tetrahydrofuran, DMF means dimethylformamide, and HATU means o-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0164] The compound of the present invention or its starting compound produced as described above is isolated and purified in its free form or as a salt thereof. The salt can be produced by a commonly used salt formation treatment. Isolation and purification can be carried out by applying common chemical procedures such as extraction, concentration, crystallization, filtration, recrystallization, and various types of chromatography.

[0165] When the compound of the present invention or a pharmacologically acceptable salt thereof exists as an optical isomer based on an asymmetric carbon, it can be separated into individual optical isomers by conventional optical resolution methods (e.g., fractional crystallization, resolution using a chiral column). Alternatively, optical isomers can be synthesized using optically pure starting materials. Furthermore, optical isomers can be synthesized by stereoselectively carrying out each reaction using an asymmetric auxiliary group or an asymmetric catalyst.

[0166] Examples of the compound of the present invention or a pharmacologically acceptable salt thereof include, but are not limited to, the following compounds.

[0167] 1. Preparation of Example Compounds Example 1 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydro-1H-pyrido[4,3-e][1,4]diazepin-5-one

[0168] (1) To a mixture of 200 mg of 4-chloro-6-(trifluoromethyl)pyridine-3-carboxylic acid and 4.4 mL of methylene chloride, 0.113 mL of oxalyl chloride and 0.0068 mL of N,N-dimethylformamide were added. The reaction mixture was stirred at room temperature for 30 minutes, and then 0.075 mL of oxalyl chloride was added to the reaction mixture. The reaction mixture was stirred at room temperature for 15 minutes and then concentrated under reduced pressure to obtain a crude product of 4-chloro-6-(trifluoromethyl)pyridine-3-carbonyl chloride. (2) To a mixture of the crude product of 4-chloro-6-(trifluoromethyl)pyridine-3-carbonyl chloride obtained in (1) above and 2.1 mL of acetonitrile, a mixture of 200 mg of benzyl N-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propyl]carbamate and 2.1 mL of acetonitrile was added, followed by the addition of 0.18 mL of triethylamine. The reaction mixture was stirred at room temperature for 2 hours. Saturated brine and chloroform were added to the reaction mixture and stirred, after which the organic layer was separated and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 100 / 0 to 10 / 90) to obtain 178 mg of N- [(2R) -2- [ [4-chloro-6- (trifluoromethyl) pyridine-3-carbonyl] - [2- (2-fluorophenyl) sulfonyl-2-azaspiro [3.3] heptan-6-yl] amino] propyl] carbamate benzyl as a yellow powder. (3) To a mixture of 178 mg of N- [ (2R) -2- [ [4-chloro-6- (trifluoromethyl) pyridine-3-carbonyl] - [2- (2-fluorophenyl) sulfonyl-2-azaspiro [3.3] heptan-6-yl] amino] propyl] carbamate obtained in (2) above and 1.3 mL of N, N- dimethylformamide, 16.0 mg of sodium hydride (60%) was added and stirred at room temperature for 1 hour. To the reaction mixture was added 8.5 mg of sodium hydride (60%). The reaction mixture was stirred at room temperature for 30 minutes, and then saturated aqueous ammonium chloride solution was added. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was separated and concentrated under reduced pressure.The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile=70 / 30 to 40 / 60) to give 107.6 mg (yield 81%) of the title compound as a yellow powder. MS (ESI) m / z: 499 [M+H]. ＋

[0169] Examples 2 to 7: The corresponding starting compounds were treated in the same manner as in Example 1 to obtain the compounds listed in Table 1 below. However, * in the figure represents a racemic carbon. The same applies to the following tables.

[0170]

[0171] Example 8 Preparation of (7R)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydropyrazino[2,3-f][1,4]oxazepin-9-one

[0172] (1) To a mixture of 432 mg of 3-chloropyrazine-2-carboxylic acid and 7 mL of methylene chloride, 0.280 mL of oxalyl chloride and 0.020 mL of N,N-dimethylformamide were added. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain crude 3-chloropyrazine-2-carbonyl chloride. (2) To a mixture of 307 mg of (2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propan-1-ol, 0.65 mL of triethylamine, and 5.0 mL of acetonitrile, a mixture of the entire amount of 3-chloropyrazine-2-carbonyl chloride obtained in (1) above and 3.0 mL of acetonitrile was added under ice cooling. The reaction mixture was stirred at room temperature for 3.5 hours. To the reaction mixture, 8.0 mL of 1N aqueous sodium hydroxide solution was added. The reaction mixture was stirred at room temperature for 70 minutes. Saturated brine and ethyl acetate were added to the reaction mixture, and the layers were separated. The aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with saturated brine and dried over sodium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure to obtain 425 mg of crude 3-chloro-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-[(1R)-2-hydroxy-1-methyl-ethyl]pyrazine-2-carboxamide as a yellowish-brown powder. (3) To a mixture of 425 mg of the crude product of 3-chloro-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-[(1R)-2-hydroxy-1-methyl-ethyl]pyrazine-2-carboxamide obtained in (2) above and 5.0 mL of N,N-dimethylformamide, 35.3 mg of sodium hydride (60%) was added under ice-cooling, and the mixture was stirred for 40 minutes under ice-cooling. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by a saturated aqueous solution of sodium bicarbonate and saturated brine, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with saturated brine and dried over sodium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 30 / 70 to 0 / 100). When the fractions were collected and concentrated, a solid precipitated. Therefore, hexane was added, the mixture was suspended and washed, and the solid was collected by filtration.The resulting solid was dried under reduced pressure to give 258 mg of the title compound as a colorless powder (yield over two steps: 64%). MS (ESI) m / z: 433 [M+H]. ＋

[0173] Examples 9 to 39: The corresponding starting compounds were treated in the same manner as in Example 8 to give the compounds listed in Table 2 below.

[0174] Example 40 Preparation of (7R)-3-chloro-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydropyrazino[2,3-f][1,4]oxazepin-9-one

[0175] (1) To a mixture of 916 mg of 3,5-dichloropyrazine-2-carboxylic acid and 16 mL of methylene chloride, 0.530 mL of oxalyl chloride and 0.020 mL of N,N-dimethylformamide were added. The reaction mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to obtain crude 3,5-dichloropyrazine-2-carbonyl chloride. (2) To a mixture of 525 mg of (2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propan-1-ol, 1.20 mL of triethylamine, and 15.0 mL of acetonitrile, a mixture of the crude 3,5-dichloropyrazine-2-carbonyl chloride obtained in (1) above and 5.0 mL of acetonitrile was added under ice cooling. The reaction mixture was stirred at room temperature for 50 minutes. 13.0 mL of 1N aqueous sodium hydroxide solution was added to the reaction mixture. The reaction mixture was stirred at room temperature for 1 hour, and then saturated saline and ethyl acetate were added to separate the layers. The aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with saturated saline and dried over sodium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 25 / 75 to 0 / 100). The collected fractions were concentrated under reduced pressure, and the resulting residue was suspended and washed in 25 mL of a mixed solvent of diisopropyl ether:hexane = 2:3, and the solid was collected by filtration. The resulting solid was dried under reduced pressure to give 544 mg (73% yield) of the title compound as a colorless powder. MS (ESI) m / z: 467 / 469 [M+H] ＋

[0176] Examples 41 to 43: The corresponding starting compounds were treated in the same manner as in Example 40 to give the compounds listed in Table 3 below.

[0177] Example 44 Preparation of (7R)-6-[2-(2-fluorophenyl)sulfonyl]-2-azaspiro[3.3]heptan-6-yl]-7-methyl-2-(trifluoromethyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one

[0178] (1) To a mixture of 526 mg of 4-chloro-2-(trifluoromethyl)pyrimidine-5-carboxylic acid in 8.0 mL of methylene chloride, 0.300 mL of oxalyl chloride and 0.006 mL of N,N-dimethylformamide were added. The reaction mixture was stirred at room temperature for 3.5 hours and then concentrated under reduced pressure to obtain crude 4-chloro-2-(trifluoromethyl)pyrimidine-5-carbonyl chloride. (2) To a mixture of 770 mg of (2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propan-1-ol, 1.20 mL of triethylamine, and 6.0 mL of tetrahydrofuran, a mixture of the crude 4-chloro-2-(trifluoromethyl)pyrimidine-5-carbonyl chloride obtained in (1) above and 4.0 mL of tetrahydrofuran was added under ice cooling. The reaction mixture was stirred at room temperature for 2.5 hours, after which an aqueous citric acid solution was added and the mixture was extracted twice with ethyl acetate. The combined organic layers were washed with saturated brine and dried over sodium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 20 / 80) and then purified again by silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 25 / 75) to obtain 57.8 mg (yield 4.9%) of the title compound as a colorless powder. MS (ESI) m / z: 501 [M+H] ＋

[0179] Example 45 Preparation of 2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-1-methyl-4,5-dihydro-1H-2-benzazepin-3-one

[0180] To a mixture of 28.2 mg of tert-butyl 6-(1-methyl-3-oxo-4,5-dihydro-1H-2-benzazepin-2-yl)-2-azaspiro[3,3]heptane-2-carbamate and 1 mL of methylene chloride was added 0.018 mL of trimethylsilyl trifluoromethanesulfonate. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under reduced pressure. To the resulting residue were added 1 mL of methylene chloride, 23 mg of 2-fluorobenzenesulfonyl chloride, and 0.050 mL of triethylamine. The reaction mixture was stirred at room temperature for 2 hours, after which a saturated aqueous solution of sodium bicarbonate was added and the mixture was extracted twice with chloroform. The organic layers were combined and dried over sodium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 100 / 0 to 0 / 100) to obtain 258 mg of the title compound (yield: 37% over two steps) as a pale yellow viscous substance. MS (ESI) m / z: 429 [M+H] ＋

[0181] Examples 46 to 69: The corresponding starting compounds were treated in the same manner as in Example 45 to give the compounds listed in Table 4 below.

[0182] Example 70 Preparation of 4-[2-(2-fluoro-5-methyl-phenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one

[0183] A mixture of 24 mg of 4-(2-azaspiro[3.3]heptan-6-yl)-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one, 17.7 mg of 2-fluoro-5-methyl-benzenesulfonyl chloride, 0.0638 mL of N,N-diisopropylethylamine, and 1 mL of chloroform was stirred at room temperature overnight. Water was added to the reaction mixture, which was then extracted with chloroform and the organic layer was concentrated. Dimethyl sulfoxide and methanol were added to the resulting residue, and the mixture was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 30 / 70 to 0 / 100) to give 26.9 mg of the title compound (yield 69%). MS (ESI) m / z: 446 [M+H] ＋

[0184] Examples 71 to 81: The corresponding starting compounds were treated in the same manner as in Example 70 to give the compounds listed in Table 5 below.

[0185] Example 82 Preparation of 2-[2-(benzenesulfonyl)-2-azaspiro[3.3]heptan-6-yl]isoindoline-1,3-dione

[0186] 670 mg of tert-butyl 6-(1,3-dioxoisoindolin-2-yl)-2-azaspiro[3.3]heptane-2-carboxylate was weighed into a 100 mL recovery flask, and 6.0 mL of dichloromethane was added. Next, 672 mg of trimethylsilyl trifluoromethanesulfonate was added and stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure to obtain 917 mg of crude 2-(2-azaspiro[3.3]heptan-6-yl)isoindoline-1,3-dione trifluoromethanesulfonate as a colorless solid. 917 mg of the resulting crude product was weighed into a 100 mL recovery flask, and 7.0 mL of dichloromethane and 980 μL of triethylamine were added. Next, 871 mg of benzenesulfonic anhydride was added and stirred at room temperature for 20 minutes. Saturated aqueous sodium bicarbonate and ethyl acetate were added to the reaction solution, and the organic layer was extracted. The organic layer was washed with saturated brine and then dried over magnesium sulfate. After filtering off the insoluble matter, the solution was concentrated under reduced pressure. 0.86 g of the resulting pale yellow oil was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 90 / 10 to 65 / 35) to obtain 649 mg of the title compound (yield: 87% for two steps) as a colorless powder. MS (ESI) m / z: 383 [M+H] ＋

[0187] Example 83: The corresponding starting compounds were treated in the same manner as in Example 82 to give the compounds listed in Table 6 below.

[0188] Example 84 Preparation of 4-[2-(benzenesulfonyl)-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one

[0189] A mixture of 25 mg of 4-(2-azaspiro[3.3]heptan-6-yl)-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one, 32.7 mg of benzenesulfonic anhydride, and 1 mL of chloroform was stirred at room temperature overnight. The reaction mixture was concentrated, and then methanol was added. The mixture was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to give 24.3 mg (yield 64%) of the title compound. MS (ESI) m / z: 414 [M+H] ＋

[0190] Example 85 Preparation of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-2-(trifluoromethyl)-8,9-dihydro-7H-pyrido[3,2-c]azepin-5-one

[0191] 175 mg of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-2-(trifluoromethyl)-7H-pyrido[3,2-c]azepin-5-one, 80 mg of 10% palladium on carbon, 6.0 mL of ethanol, and 1.5 mL of tetrahydrofuran were weighed out and stirred at room temperature under a hydrogen atmosphere for 2 hours. The reaction mixture was diluted with chloroform, and insoluble matter was removed by filtration through Celite. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 90 / 10 to 50 / 50) to afford 160.4 mg (yield 91%) of the title compound as a colorless powder. MS (ESI) m / z: 498 [M+H] ＋

[0192] Examples 86 to 108: The corresponding starting compounds were treated in the same manner as in Example 85 to give the compounds listed in Table 7 below.

[0193] Example 109 (6R)-2-(1-fluorocyclopropyl)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-thiazolo[5,4-c]azepin-4-one and Example 110 Preparation of (6R)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-isopropyl-6-methyl-7,8-dihydro-6H-thiazolo[5,4-c]azepin-4-one

[0194] 175 mg of (6R)-2-(1-fluorocyclopropyl)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-6H-thiazolo[5,4-c]azepin-4-one was weighed into a 100 mL recovery flask and dissolved in 1.0 mL of tetrahydrofuran and 4.0 mL of ethanol. Next, 90.1 mg of 10% palladium on carbon (type M hydrous) was added, and the mixture was stirred for 135 minutes at room temperature under a hydrogen atmosphere. The reaction mixture was diluted with chloroform and then filtered through Celite. After washing with chloroform, the filtrate was concentrated under reduced pressure. The resulting pale yellow amorphous solid (0.17 g) was purified by reverse phase HPLC (solvent: 10 mM aqueous ammonium carbonate solution / acetonitrile = 60 / 40 to 50 / 50) to give 127 mg (72% yield) of (6R)-2-(1-fluorocyclopropyl)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-thiazolo[5,4-c]azepin-4-one. MS (ESI) m / z: 494 [M+H] ＋ At the same time, 19.3 mg (yield 11%) of (6R)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-isopropyl-6-methyl-7,8-dihydro-6H-thiazolo[5,4-c]azepin-4-one was obtained. MS (ESI) m / z: 478 [M+H] ＋

[0195] Example 111 Preparation of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-2-(trifluoromethyl)-7H-pyrido[3,2-c]azepin-5-one

[0196] A mixture of 346 mg of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-(1-methylallyl)-2-vinyl-pyridine-3-carboxamide, 40 mg of second-generation Grubbs catalyst, and 6.0 mL of toluene was stirred at 60°C for 1.5 hours. 19.8 mg of second-generation Grubbs catalyst was added to the reaction mixture, and the mixture was stirred at 60°C for 30 minutes. The reaction mixture was returned to room temperature, filtered through Celite and silica gel, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 90 / 10 to 60 / 40) to yield 262.3 mg of the title compound as a colorless powder. MS (ESI) m / z: 496 [M+H] ＋

[0197] Examples 112 to 132: The corresponding starting compounds were treated in the same manner as in Example 111 to give the compounds listed in Table 8 below.

[0198] Example 133 (2R ＊ , 4S ＊ , 5R ＊ Preparation of 2-(2-fluorophenyl)-10-cyclopropyl-3,3-difluoro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methyl-9-thia-6,11-diazatricyclo[6.3.0.02.4]undeca-1(8),10-dien-7-one

[0199] 128 mg of 2-cyclopropyl-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-6H-thiazolo[5,4-c]azepin-4-one was weighed into a 100 mL recovery flask and 4.0 mL of tetrahydrofuran was added. Next, 15.9 mg of sodium iodide and 120 μL of (trifluoromethyl)trimethylsilane were added, and the mixture was heated under reflux and stirred for 110 minutes. An additional 180 μL of (trifluoromethyl)trimethylsilane was then added, and the mixture was heated under reflux and stirred for 150 minutes. Next, the reaction solution was transferred to a 5 mL test tube for microwave reaction, and 1.0 mL of tetrahydrofuran, 14.6 mg of sodium iodide, and 180 μL of (trifluoromethyl)trimethylsilane were added. The mixture was stirred at 100°C for 1 hour using a microwave reactor. The reaction solution was diluted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. After filtering off the insoluble matter, the solution was concentrated under reduced pressure. The resulting yellow-brown viscous oil (141 mg) was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to give 25.9 mg (yield 18%) of the title compound as a colorless amorphous solid. MS (ESI) m / z: 524 [M+H] ＋

[0200] Example 134 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-morpholino-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one

[0201] (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one 100 mg, morpholine 21 mg, dicyclohexyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane 10 mg, tris(dibenzylideneacetone)dipalladium 6 mg, sodium tert-butoxide 31 mg was suspended in 1,4-dioxane 1.5 mL, stirred for 2 hours at an external temperature of 80 ° C., and then stirred for 2 hours at an external temperature of 90 ° C. 21 mg of morpholine was added and stirred for 2 hours at an external temperature of 90 ° C. To the reaction mixture, 10 mg of dicyclohexyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane and 6 mg of tris(dibenzylideneacetone)dipalladium were added, and the mixture was stirred at an external temperature of 90°C for 1 hour. 3 mg of sodium tert-butoxide was added to the reaction mixture, and the mixture was stirred at an external temperature of 90°C for 1 hour. The reaction mixture was extracted with saturated aqueous ammonium chloride and chloroform, the solvent was evaporated, and the residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60), followed by silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 0 / 100) to obtain 32 mg (yield 29%) of the title compound as a colorless powder. MS (ESI) m / z: 517 [M+H] ＋

[0202] Examples 135 to 161: The corresponding starting compounds were treated in the same manner as in Example 134 to give the compounds listed in Table 9 below.

[0203] Example 162 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-8-[(3S)-3-fluoropyrrolidin-1-yl]-3-methyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-5-one

[0204] 88 mg of (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one, 37 mg of (3S)-3-fluoropyrrolidine hydrochloride, 28 mg of tris(dibenzylideneacetone)dipalladium, 22 mg of dicyclohexyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane, and 57 mg of sodium t-butoxide were suspended in 2 mL of 1,4-dioxane and stirred at 90°C for 2.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 60 / 40 to 20 / 80). This was purified again by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 60 / 40 to 30 / 70) to obtain a crude product of the title compound. A crude product containing benzyl (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-8-[(3S)-3-fluoropyrrolidin-1-yl]-3-methyl-5-oxo-2,3-dihydropyrido[2,3-e][1,4]diazepine-1-carboxylate was also obtained. To this was added 2 mL of methanol and 2 mL of 1 mol / L aqueous sodium hydroxide solution, and the mixture was stirred at 70°C for 2.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was combined with the crude product of the title compound obtained by the previous column chromatography purification and purified again by silica gel column chromatography (solvent: hexane / ethyl acetate = 60 / 40 to 30 / 70) to obtain 13 mg (yield 17%) of the title compound as a colorless powder. MS (ESI) m / z: 518 [M+H] ＋

[0205] Example 163 (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-8-methoxy-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one and Example 164 Preparation of (3R)-8-methoxy-4-[2-(2-methoxyphenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one

[0206] 77.8 mg of (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one was dissolved in 1.6 mL of methanol, and 47.8 μL of sodium methoxide (5 mol / L methanol solution) was added, followed by heating under reflux for 3 hours. 31.9 μL of sodium methoxide (5 mol / L methanol solution) was added to the reaction mixture, followed by heating under reflux for 0.5 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. Water was added to the resulting residue, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 33 / 67 to 25 / 75) to obtain 45.7 mg (yield 62%) of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-8-methoxy-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one as a colorless powder. MS (ESI) m / z: 462 [M+H] ＋ At the same time, 14.1 mg (yield 19%) of (3R)-8-methoxy-4-[2-(2-methoxyphenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one was obtained as a colorless powder. MS (ESI) m / z: 474 [M+H] ＋

[0207] Examples 165-166: The corresponding starting compounds were treated in the same manner as in Examples 163 and 164 to give the compounds listed in Table 10 below.

[0208] Example 167 Preparation of (3R)-7-fluoro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-8-methoxy-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one

[0209] (1) 403 mg of 2,6-dichloro-5-fluoro-pyridine-3-carboxylic acid was weighed into a 50 mL recovery flask and 7 mL of dichloromethane was added. Next, 175 μL of oxalyl chloride and 20 μL of N,N-dimethylformamide were added, and the mixture was stirred at room temperature for 75 minutes. The reaction mixture was concentrated under reduced pressure to obtain crude 2,6-dichloro-5-fluoro-pyridine-3-carboxylic acid chloride. (2) The crude product obtained in (1) was dissolved in 9.0 mL of acetonitrile in a 50 mL recovery flask, and 206 mg of (2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propan-1-ol and 350 μL of triethylamine were added, followed by stirring at room temperature for 100 minutes. Subsequently, 5.0 mL of 1N aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was stirred at room temperature for 80 minutes. Ethyl acetate, saturated aqueous sodium bicarbonate, and saturated saline were added to the reaction mixture, and the organic layer was extracted. The organic layer was washed with saturated saline and then dried over magnesium sulfate. After filtering off insoluble matter, the solution was concentrated under reduced pressure. 0.40 g of the resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 65 / 35 to 30 / 70) to obtain 260 mg of 2,6-dichloro-5-fluoro-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-[(1R)-2-hydroxy-1-methyl-ethyl]pyridine-3-carboxamide (yield: 80% for two steps) as a pale yellow solid. MS (ESI) m / z: 520 [M+H] ＋(3) 259 mg of 2,6-dichloro-5-fluoro-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-[(1R)-2-hydroxy-1-methyl-ethyl]pyridine-3-carboxamide obtained in (2) was weighed into a 100 mL recovery flask, and 5.0 mL of N,N-dimethylformamide was added. Under ice cooling, 26.0 mg of sodium hydride (60%) was added and stirred for 1 hour. An additional 23.7 mg of sodium hydride (60%) was then added and stirred for 45 minutes under ice cooling. Next, 100 μL of methanol was added and the mixture was stirred for 15 minutes under ice cooling. A saturated aqueous solution of ammonium chloride and saturated saline were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over magnesium sulfate. After filtering off insoluble matter, the solution was concentrated under reduced pressure. 0.35 g of the resulting pale yellow oil was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 70 / 30 to 25 / 75) to give 104 mg of a colorless oil. This was further purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to give 76.1 mg (32% yield) of the title compound as a colorless amorphous solid. MS (ESI) m / z: 480 [M+H] ＋

[0210] Example 168 (7R)-2-[(1S ＊ , 5R ＊ Preparation of 5,4-f-3-azabicyclo[3.1.0]hexan-3-yl]-6-[2-(2-fluorophenyl)sulfonyl]-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one

[0211] 50 mg of (7R)-2-chloro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-2-yl]-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one, 16 mg of 3-azabicyclo[3.1.0]hexane hydrochloride, and 46 μL of N,N-diisopropylethylamine were dissolved in 1 mL of N,N-dimethylformamide and stirred at room temperature for 0.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 80 / 20 to 0 / 100) to afford 42 mg (yield 91%) of the title compound as a colorless powder. MS (ESI) m / z: 514 [M+H] ＋

[0212] Example 169: The corresponding starting compounds were treated in the same manner as in Example 168 to give the compounds listed in Table 11 below.

[0213] Example 170 Preparation of (6R)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-1,6-dimethyl-6,7-dihydropyrazolo[4,3-f][1,4]oxazepin-4-one

[0214] (1) To a mixture of 750 mg of ethyl 5-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propoxy]-1-methyl-pyrazole-4-carboxylate, 4.70 mL of ethanol, and 4.70 mL of tetrahydrofuran, 4.70 mL of 1N aqueous sodium hydroxide was added. The reaction mixture was stirred at 70°C for 2 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure to obtain crude sodium 5-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propoxy]-1-methyl-pyrazole-4-carboxylate. (2) To a mixture of 10 mL of N,N-dimethylformamide with the crude product obtained in (1) above, 890 mg of HATU and 0.410 mL of N,N-diisopropylethylamine were added. The reaction mixture was stirred at room temperature for 30 minutes. Water and ethyl acetate were added to the reaction mixture, and the layers were separated. The aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with saturated brine and dried over magnesium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 95 / 5). When the fractions were collected and concentrated, a solid precipitated. Therefore, an ethyl acetate-hexane mixed solvent (4:6) was added, and the mixture was suspended and washed, and the solid was collected by filtration. The resulting solid was dried under reduced pressure to give 301 mg of the title compound (yield: 44% for two steps) as a colorless powder. MS (ESI) m / z: 435 [M+H] ＋

[0215] Examples 171 to 233: The corresponding starting compounds were treated in the same manner as in Example 170 to give the compounds listed in Table 12 below.

[0216] Example 234 (6R)-2-[(1S,2R)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one and Example 235 Preparation of (6R)-2-[(1R,2R)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one

[0217] 390 mg of 2-[(1S,2R)-2-fluorocyclopropyl]-4-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propoxy]thiazole-5-carboxylic acid ethyl ester was weighed into a 100 mL recovery flask and dissolved in 1.5 mL of ethanol and 2.5 mL of tetrahydrofuran. Next, 1.50 mL of 1 N aqueous sodium hydroxide solution was added and the mixture was stirred at room temperature for 12 hours. 1.50 mL of 1 N hydrochloric acid was added to the reaction solution, and the solvent was concentrated under reduced pressure. 4.0 mL of N,N-dimethylformamide was added, followed by 364 mg of HATU and 350 μL of N,N-diisopropylethylamine, in that order, and the mixture was stirred at room temperature for 140 minutes. Ethyl acetate, saturated aqueous sodium bicarbonate, and saturated saline were added to the reaction solution, and the organic layer was extracted. The organic layer was washed with saturated saline and then dried over magnesium sulfate. After filtering off the insoluble matter, the solution was concentrated under reduced pressure. 0.62 g of the resulting orange oil was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 70 / 30 to 25 / 75). The highly polar (Rf ∼ 0.2) spot on the thin layer chromatography (solvent: hexane / ethyl acetate = 1:2) side was collected and concentrated to obtain 125 mg of a pale yellow amorphous solid. This was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to obtain 91.0 mg (26% yield over two steps) of the title compound (6R)-2-[(1S,2R)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one as a colorless amorphous solid. MS (ESI) m / z: 496 [M+H] ＋At the same time, by silica gel column chromatography, spots on the low polarity side (Rf ∼0.4) by thin layer chromatography (solvent: hexane / ethyl acetate = 1:2) were collected and concentrated to obtain 230 mg (64% yield over two steps) of the title compound (6R)-2-[(1R,2R)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one as a colorless amorphous solid. MS (ESI) m / z: 496 [M+H] ＋

[0218] Example 236 Preparation of (6R)-2-[(1R,2S)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one and Example 237 Preparation of (6R)-2-[(1S,2S)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one

[0219] The reaction was carried out according to the method of Example 234 using 387 mg of 2-[(1R,2S)-2-fluorocyclopropyl]-4-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propoxy]thiazole-5-carboxylic acid ethyl ester to give 0.58 g of crude product as an orange oil. This was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 70 / 30 to 25 / 75). The spot on the more polar side (Rf ∼0.3) of thin layer chromatography (solvent: hexane / ethyl acetate = 1:2) was collected and concentrated to give 174 mg of a yellow amorphous solid. This was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to obtain 119 mg of the title compound (6R)-2-[(1R,2S)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one (yield: 34% over two steps) as a colorless amorphous solid. MS (ESI) m / z: 496 [M+H] ＋ At the same time, by silica gel column chromatography, spots on the low polarity side (Rf ∼0.5) by thin layer chromatography (solvent: hexane / ethyl acetate = 1:2) were collected and concentrated to obtain 186 mg of the title compound (6R)-2-[(1S,2S)-2-fluorocyclopropyl]-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one (yield: 53% over two steps) as a colorless amorphous solid. MS (ESI) m / z: 496 [M+H] ＋

[0220] Example 238 Preparation of (6R)-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-3-(trifluoromethyl)-5,6-dihydroimidazo[1,5-a]pyrazin-8-one

[0221] 57.9 mg of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-[(1R)-2-hydroxy-1-methyl-ethyl]-2-(trifluoromethyl)-1H-imidazole-5-carboxamide and 38 mg of triphenylphosphine were placed in a 30 mL recovery flask and dissolved in 1 mL of toluene and 1 mL of tetrahydrofuran. 34 mg of bis(2-methoxyethyl) azodicarboxylate was added and stirred at room temperature for 0.5 hours. Saturated saline was added, and the mixture was extracted with ethyl acetate. The organic layer was filtered and concentrated. The resulting residue was purified by silica gel chromatography (solvent: hexane / ethyl acetate = 70 / 30 to 10 / 90) and further purified by reverse-phase HPLC preparative HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to afford 5.3 mg (yield 9.5%) of the title compound as a pale yellow viscous oil. MS (ESI) m / z: 473 [M+H] ＋

[0222] Example 239 Preparation of 4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro-1,4-benzoxazepin-5-one

[0223] 150 mg of 3-methyl-3,4-dihydro-2H-1,4-benzoxazepin-5-one was dissolved in 5 mL of N,N-dimethylformamide, and 34 mg of sodium hydride (60%) was added. 300 mg of [2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-4-methylbenzenesulfonate was added, and the mixture was stirred at 80°C for 2 hours. The temperature was raised to 110°C and stirred for 1 hour. The temperature was raised to 130°C and stirred for 10 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dimethyl sulfoxide and purified by reverse phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70), followed by silica gel column chromatography (solvent: hexane / ethyl acetate = 75 / 25 to 55 / 45) to give 7 mg (yield 2%) of the title compound as a colorless powder. MS (ESI) m / z: 431 [M+H] ＋

[0224] Examples 240 to 244: The corresponding starting compounds were treated in the same manner as in Example 239 to give the compounds listed in Table 13 below.

[0225] Example 245 Preparation of (3R)-1-ethyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-e][1,4]diazepin-5-one

[0226] 20 mg of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro-1H-pyrido[3,2-e][1,4]diazepin-5-one was dissolved in 1 mL of dichloromethane, 3.9 μL of acetaldehyde was added, and the mixture was stirred at room temperature for 15 minutes. 16.7 mg of sodium triacetoxyborohydride was then added and stirred for 1 hour. 26.2 μL of acetaldehyde and 19.7 mg of sodium triacetoxyborohydride were then added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. 13.1 μL of acetaldehyde and 19.7 mg of sodium triacetoxyborohydride were then added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was stirred. The organic layer was then separated using a Phase-separator® and concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 90 / 10) to obtain 19.9 mg (yield 93%) of the title compound as a bright yellow powder. MS (ESI) m / z: 459 [M+H] ＋

[0227] Example 246: The corresponding starting compounds were treated in the same manner as in Example 245 to give the compounds listed in Table 14 below.

[0228] Example 247 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-1,3-dimethyl-8-(trifluoromethyl)-2,3-dihydropyrido[2,3-e][1,4]diazepin-5-one

[0229] A 10 mL recovery flask was charged with 16.2 mg of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-5-one and dissolved in 0.5 mL of N,N-dimethylformamide. Under ice-cooling, 4 mg of sodium hydride and 0.010 mL of iodomethane were added, followed by stirring at room temperature for 18 hours. Saturated aqueous ammonium chloride and ethyl acetate were added to the reaction mixture, and the layers were separated. The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in dimethyl sulfoxide and purified by reverse-phase HPLC preparative analysis (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 50 / 50 to 20 / 80) to obtain 7.7 mg (46% yield) of the title compound as a pale yellow powder. MS (ESI) m / z: 513 [M+H] ＋

[0230] Example 248: The corresponding starting compounds were treated in the same manner as in Example 247 to give the compounds listed in Table 15 below.

[0231] Example 249 Preparation of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-methoxy-7-methyl-8,9-dihydro-7H-pyrido[3,2-c]azepin-5-one

[0232] 40 mg of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,7,8,9-tetrahydropyrido[3,2-c]azepine-2,5-dione was dissolved in 1 mL of N,N-dimethylformamide, and 5.4 mg of sodium hydride (60%) was added. 11.2 μL of methyl iodide was added thereto, and the mixture was stirred at room temperature for 0.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dimethyl sulfoxide and purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to give 36 mg (yield 87%) of the title compound as a colorless powder. MS (ESI) m / z: 460 [M+H] ＋

[0233] Example 250 Preparation of 2-[2-benzenesulfonyl-2-azaspiro[3.3]heptan-6-yl]-1-ethyl-indazol-3-one

[0234] 80 mg of 2-[2-benzenesulfonyl-2-azaspiro[3.3]heptan-6-yl]-1H-indazol-3-one was dissolved in 2 mL of N,N-dimethylformamide, and 60 mg of potassium carbonate and 26.0 μL of ethyl iodide were added, followed by stirring at 100°C for 1.5 hours. The reaction solution was dissolved in dimethyl sulfoxide and purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to obtain 65 mg (76% yield) of the title compound as a brown oil. MS (ESI) m / z: 398 [M+H] ＋

[0235] Example 251 Preparation of (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-5-one and Example 252 Preparation of benzyl (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-5-oxo-2,3-dihydropyrido[2,3-e][1,4]diazepine-1-carboxylate

[0236] (1) 430 mg of 2,6-dichloropyridine-3-carboxylic acid was dissolved in 11 mL of dichloromethane, and 284 μL of oxalyl chloride was added. Then, 17.3 μL of N,N-dimethylformamide was added and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure to obtain a crude product of 2,6-dichloropyridine-3-carbonyl chloride as a yellow viscous substance. (2) The crude product of 2,6-dichloropyridine-3-carbonyl chloride obtained in (1) above was dissolved in 5.4 mL of acetonitrile, and a solution of 500 mg of benzyl N-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propyl]carbamate in acetonitrile (5.4 mL) was added, followed by the addition of 452 μL of triethylamine and stirring at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate and chloroform were added to the reaction mixture and stirred. The organic layer was then separated using a Phase-Separator® and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 100 / 0 to 20 / 80) to yield 579 mg of benzyl N-[(2R)-2-[(2,6-dichloropyridine-3-carbonyl)-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propyl]carbamate as a yellow powder. (3) 579 mg of benzyl N-[(2R)-2-[(2,6-dichloropyridine-3-carbonyl)-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propyl]carbamate obtained in (2) above was dissolved in 4.6 mL of N,N-dimethylformamide, and 54.7 mg of sodium hydride (60%) was added, followed by stirring at room temperature for 5 hours. A saturated aqueous solution of ammonium chloride was added to the reaction solution to terminate the reaction. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, then separated using a Phase-separator®, and concentrated under reduced pressure.The resulting residue was purified by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 15 / 85) and then again by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 20 / 80) to give 81.1 mg (two-step yield 16%) of (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-5-one as a colorless powder. MS (ESI) m / z: 465 / 467 [M+H]. ＋ At the same time, 47.6 mg (8.7% yield in two steps) of benzyl (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro[2,3-e][1,4]diazepine-1-carboxylate was obtained as a yellow powder. MS (ESI) m / z: 599 / 601 [M+H] ＋

[0237] Examples 253 to 257: The corresponding starting compounds were treated in the same manner as in Example 251 to give the compounds listed in Table 16 below.

[0238] Example 258 Preparation of (3R)-8-cyclopropyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-5-one

[0239] To 45 mg of benzyl (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-5-oxo-2,3-dihydropyrido[2,3-e][1,4]diazepine-1-carboxylate, 1 mL of toluene and 60 μL of water were added, followed by the addition of 9.7 mg of cyclopropylboronic acid, 5.5 mg of bis(tricyclohexylphosphine)palladium(II) dichloride, and 47.8 mg of potassium phosphate, and the mixture was stirred at 130 °C for 2 hours. An additional 6.5 mg of cyclopropylboronic acid and 5.5 mg of bis(tricyclohexylphosphine)palladium(II) dichloride were added to the reaction mixture, and the mixture was stirred at 130 °C for 2 hours. The reaction mixture was cooled to room temperature, and water and chloroform were added and stirred. The organic layer was then separated using a Phase-separator® and concentrated under reduced pressure. The resulting residue was dissolved in 2 mL of methanol, and 0.75 mL of 1 N aqueous sodium hydroxide was added. The mixture was stirred overnight at room temperature. An additional 0.38 mL of 1 N aqueous sodium hydroxide was then added to the reaction mixture, followed by stirring at 80°C for 3 hours. The reaction mixture was cooled to room temperature, and water and chloroform were added and stirred. The organic layer was separated using a Phase-Separator® and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 100 / 0 to 20 / 80). The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70) to give 13.5 mg of the title compound (yield: 38% for two steps) as a colorless powder. MS (ESI) m / z: 471 [M+H] ＋

[0240] Example 259 Preparation of 4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[3,2-f][1,4]thiazepin-5-one

[0241] 380.4 mg of 2-chloro-N-[2-[2-[[2-chloro-6-(trifluoromethyl)pyridine-3-carbonyl]-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propyldisulfanyl]-1-methyl-ethyl]-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-(trifluoromethyl)pyridine-3-carboxamide was placed in a 50 mL recovery flask and dissolved in 5 mL of dimethylformamide. 70 mg of sodium hydride was added under ice cooling, and the mixture was then warmed to room temperature. Subsequently, 60 mg of sodium borohydride was added, and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of ammonium chloride was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in dimethyl sulfoxide and purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70) to obtain 14.7 mg (yield 8.3%) of the title compound as a pale yellow powder. MS (ESI) m / z: 516 [M+H] ＋

[0242] Example 260 Preparation of (7R)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3,7-dimethyl-6,7-dihydro-5H-[1,2,4]triazolo[4,3-a][1,4]diazepin-9-one

[0243] To a mixture of 60.0 mg of (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-3-thioxo-1,4-diazepin-2-one and 2.00 mL of 1-butanol, 90.0 mg of acetohydrazine was added. The reaction mixture was stirred at 160°C for 6 hours. After cooling to room temperature, water and chloroform were added to the reaction mixture and the layers were separated. The aqueous layer was extracted again with chloroform. The combined organic layers were washed with saturated brine and dried over magnesium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: chloroform / methanol = 100 / 0 to 95 / 5). When the fractions were collected and concentrated, a solid precipitated. Therefore, ethyl acetate was added, the mixture was suspended and washed, and the solid was collected by filtration. The resulting solid was dried under reduced pressure to give 23.1 mg (yield 37%) of the title compound as a colorless powder. MS (ESI) m / z: 434 [M+H] ＋

[0244] Examples 261 to 265: The corresponding starting compounds were treated in the same manner as in Example 260 to give the compounds listed in Table 17 below.

[0245] Example 266 Preparation of 2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-isoindolin-1-one

[0246] 82.3 mg of 2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-hydroxy-3-methyl-isoindolin-1-one was weighed into a 10 mL recovery flask and dissolved in 2.0 mL of dichloromethane. This solution was cooled in a dry ice-acetone bath (external temperature -78°C), and 130 μL of triethylsilane and then 50 μL of boron-trifluoride diethyl ether complex were added. The temperature was then raised and the mixture was stirred for 40 minutes under ice cooling. Saturated saline was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate. After filtering off insoluble matter, the solution was concentrated under reduced pressure. 0.09 g of the resulting colorless oil was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 80 / 20 to 50 / 50) to obtain 56.4 mg (71% yield) of the title compound as a colorless powder. MS (ESI) m / z: 401 [M+H] ＋

[0247] Examples 267 to 274: The corresponding starting compounds were treated in the same manner as in Example 266 to give the compounds listed in Table 18 below.

[0248] Example 275 Preparation of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-hydroxy-5-methyl-3-(trifluoromethyl)pyrrolo[3,4-b]pyridin-7-one

[0249] 579 mg of 3-bromo-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-(trifluoromethyl)pyridine-2-carboxamide was weighed into a 100 mL recovery flask, and 8.0 mL of 1,4-dioxane was added. Next, 600 μL of tributyl(1-ethoxyvinyl)tin and 196 mg of tetrakistriphenylphosphinepalladium were added, and the mixture was heated and stirred at 100°C under a nitrogen atmosphere for 24 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered through Celite. The organic layer was washed with saturated brine and then dried over magnesium sulfate. Insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure. The resulting 1.41 g of yellowish-brown oil was purified by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 80 / 20 to 45 / 55) to yield 455 mg of crude 3-(1-ethoxyvinyl)-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-(trifluoromethyl)pyridine-2-carboxamide as a pale yellow solid. 455 mg of the resulting crude product was weighed into a 100 mL recovery flask and dissolved in 10 mL of tetrahydrofuran. 2.0 mL of 1N hydrochloric acid was then added, and the mixture was stirred at room temperature for 3 hours. Ethyl acetate and saturated aqueous sodium bicarbonate were added to the reaction mixture, and the organic layer was extracted. The organic layer was washed with saturated brine and then dried over magnesium sulfate. After filtering off insoluble matter, the solution was concentrated under reduced pressure. The resulting pale yellow solid was suspended and washed in 20 mL of diisopropyl ether, and the solid was collected by filtration and dried under reduced pressure to give 373 mg of the title compound (yield: 69% for two steps) as a colorless powder. MS (ESI) m / z: 486 [M+H] ＋

[0250] Examples 276 to 282: The corresponding starting compounds were treated in the same manner as in Example 275 to give the compounds listed in Table 19 below.

[0251] Example 283 Preparation of 2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-hydroxy-3-methyl-isoindolin-1-one

[0252] 223 mg of 2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]isoindoline-1,3-dione was weighed into a 50 mL recovery flask, and 6.0 mL of tetrahydrofuran was added. The mixture was stirred under ice cooling. 2.0 mL of a 1 mol / L methylmagnesium bromide tetrahydrofuran solution was then added and the mixture was stirred under ice cooling for 105 minutes. Aqueous ammonium chloride solution and saturated brine were added to the reaction mixture. The mixture was extracted with ethyl acetate, washed with saturated brine, and dried over magnesium sulfate. After filtering out insoluble matter, the solution was concentrated under reduced pressure. 0.29 g of the resulting colorless solid was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 75 / 25 to 30 / 70) to obtain 216 mg (93% yield) of the title compound as a colorless powder. MS (ESI) m / z: 417 [M+H] ＋

[0253] Examples 284 to 289: The corresponding starting compounds were treated in the same manner as in Example 283 to give the compounds listed in Table 20 below.

[0254] Example 290 Preparation of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methyl-3-(trifluoromethyl)-5H-pyrrolo[3,4-b]pyridin-7-one

[0255] 321 mg of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-hydroxy-5-methyl-3-(trifluoromethyl)pyrrolo[3,4-b]pyridin-7-one was weighed into a 50 mL recovery flask and 6.0 mL of dichloromethane was added. Next, 219 mg of methanesulfonic anhydride and 500 μL of triethylamine were added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and saturated brine, and then dried over magnesium sulfate. After filtering off insoluble matter, the solution was concentrated under reduced pressure to yield 327 mg of crude 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methylene-3-(trifluoromethyl)pyrrolo[3,4-b]pyridin-7-one as a colorless solid. 327 mg of the resulting crude product was weighed into a 100 mL recovery flask, and 8.0 mL of ethanol and 2.0 mL of tetrahydrofuran were added. Next, 304 mg of 5% palladium / carbon (aqueous) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 7 hours. The reaction solution was diluted with 20 mL of chloroform and then filtered through Celite. After washing with 40 mL of chloroform, the filtrate was concentrated under reduced pressure. 0.34 g of the resulting pale yellow oil was purified by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 55 / 45 to 30 / 70) to give 251 mg of the title compound (yield: 81% for two steps) as a colorless solid. MS (ESI) m / z: 470 [M+H] ＋

[0256] Examples 291 to 295: The corresponding starting compounds were treated in the same manner as in Example 290 to give the compounds listed in Table 21 below.

[0257] Example 296 Preparation of 2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-1-methyl-1H-pyrrolo[3,4-c]pyridin-3-one

[0258] 150 mg of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-amine and 100 mg of methyl 4-acetylpyridine-3-carboxylate were dissolved in 5 mL of tetrahydrofuran, 473 mg of tetraisopropyl orthotitanate was added, and the mixture was stirred at room temperature for 14 hours. 471 mg of sodium triacetoxyborohydride was added to the reaction solution, and the mixture was heated to 50°C and stirred for 1 hour. The reaction solution was diluted with chloroform, NH silica gel was added, and the mixture was concentrated under reduced pressure. This was purified by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 0 / 100) to obtain 155 mg (70% yield) of the title compound as a colorless oil. MS (ESI) m / z: 402 [M+H] ＋

[0259] Example 297 Preparation of (6R)-3-bromo-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydroisoxazolo[3,4-f][1,4]oxazepin-8-one

[0260] 163 mg of (6R)-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydroisoxazolo[3,4-f][1,4]oxazepin-8-one was dissolved in 3 mL of acetonitrile, and 1-bromopyrrolidine-2,5-dione was added and stirred at room temperature for 2 hours. After further stirring at 50°C for 3 hours, room temperature for 15 hours, and 50°C for 2 hours, water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 75 / 25 to 20 / 80) to afford 69 mg (yield 36%) of the title compound as a colorless powder. MS (ESI) m / z: 500 / 502 [M+H] ＋

[0261] Examples 298-299: The corresponding starting compounds and reagents were treated in the same manner as in Example 297 to give the compounds listed in Table 22 below.

[0262] Example 300 9,9-difluoro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrido[3,2-c]azepin-5-one and Example 301 Preparation of 9-fluoro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7H-pyrido[3,2-c]azepin-5-one

[0263] 80 mg of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrido[3,2-c]azepine-5,9-dione was dissolved in 2 mL of chloroform, and 0.166 mL of bis(2-methoxyethyl)aminosulfur trifluoride was added. The mixture was stirred at 50°C for 1 hour. A saturated aqueous solution of sodium hydride was added to the reaction mixture, which was then extracted with chloroform. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 35 / 65 to 30 / 70) to obtain 34 mg (40% yield) of 9,9-difluoro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrido[3,2-c]azepin-5-one as a colorless powder. MS (ESI) m / z: 466 [M+H] ＋ Furthermore, 9 mg (yield 11%) of 9-fluoro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7H-pyrido[3,2-c]azepin-5-one was obtained as a colorless powder. MS (ESI) m / z: 446 [M+H] ＋

[0264] Example 302 Preparation of (3R)-1-acetyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-e][1,4]diazepin-5-one

[0265] 15 mg of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro-1H-pyrido[3,2-e][1,4]diazepin-5-one was dissolved in 1 mL of chloroform, and 18.1 μL of N,N-diisopropylethylamine was added and the mixture was ice-cooled. 5.0 μL of acetyl chloride was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. 2.5 μL of acetyl chloride was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was stirred. The organic layer was separated using a Phase-separator® and concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 95 / 5) and then purified again by silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 90 / 10) to give 10.7 mg (yield 65%) of the title compound as a colorless powder. MS (ESI) m / z: 473 [M+H] ＋

[0266] Examples 303 to 308: The corresponding starting compounds were treated in the same manner as in Example 302 to give the compounds listed in Table 23 below.

[0267] Example 309 (7R)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepin-9-one and Example 310 Preparation of (7R)-1-cyclohexyl-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepin-9-one

[0268] 100 mg of (7R)-1-bromo-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepin-9-one, 25.9 mg of cyclopropaneboronic acid, 14.8 mg of dichlorobis(tricyclohexylphosphine)palladium, and 85.4 mg of potassium phosphate were suspended in 2 mL of toluene and 0.4 mL of water and stirred at 110°C for 7 hours. 25.9 mg of cyclopropaneboronic acid, 14.8 mg of dichlorobis(tricyclohexylphosphine)palladium, and 85.4 mg of potassium phosphate were added to the reaction mixture and stirred at 110°C for 4 hours. The reaction mixture was returned to room temperature, water was added, and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. To the resulting residue, 44.6 mg of potassium cyclopropyltrifluoroborate, 6.8 mg of palladium acetate, 7.2 mg of butyldi-1-adamantylphosphine, and 131 mg of cesium carbonate were added, and the mixture was suspended in 2 mL of toluene and 0.3 mL of water. The mixture was stirred at 110°C for 8 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dimethyl sulfoxide and purified by reverse phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60), followed by NH silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 94 / 6) to obtain 5.4 mg (6.4% yield) of (7R)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepin-9-one as a colorless powder. MS (ESI) m / z: 419 [M+H] ＋Furthermore, the residue was purified again by silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 90 / 10) to obtain 3.2 mg (yield 3.5%) of (7R)-1-cyclohexyl-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepin-9-one as a colorless powder. MS (ESI) m / z: 459 [M+H] ＋

[0269] Examples 311 to 330: The corresponding starting compounds and reagents were treated in the same manner as in Example 310 to give the compounds listed in Table 24 below.

[0270] Example 331 Preparation of (7R)-2-cyclopropyl-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one To a mixture of 91 mg of (7R)-2-chloro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one, 10 mg of [(2-dicyclohexylphosphino-2',6'-bis(N,N-dimethylamino)-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium methanesulfonate and 2 mL of tetrahydrofuran, 0.80 mL of a 0.5 mol / L bromo(cyclopropyl)zinc tetrahydrofuran solution was added under a nitrogen atmosphere, and the mixture was stirred at 60°C for 1.5 hours. To the reaction mixture, 22 mg of [(2-dicyclohexylphosphino-2',6'-bis(N,N-dimethylamino)-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium methanesulfonate and 0.80 mL of a 0.5 mol / L solution of bromo(cyclopropyl)zinc in tetrahydrofuran were added, and the mixture was stirred at 60°C for 30 minutes. The reaction mixture was returned to room temperature, saturated aqueous sodium bicarbonate was added, and the mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and then dried over magnesium sulfate. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 20 / 80) and then recrystallized using hexane-ethyl acetate. The solid was collected by filtration and dried under reduced pressure to obtain 46 mg (yield 50%) of the title compound as a colorless powder. MS (ESI) m / z: 473 [M+H] ＋

[0271] Example 332 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-5-oxo-2,3-dihydropyrido[2,3-f][1,4]oxazepine-8-carbonitrile

[0272] 94 mg of (3R)-8-bromo-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one, 32 mg of zinc cyanide, and 21 mg of tetrakistriphenylphosphine palladium were suspended in 2 mL of dimethylformamide and stirred at 110°C for 11 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated, and the resulting residue was dissolved in 2 mL of dimethylformamide. 97 mg of zinc cyanide and 42 mg of tetrakistriphenylphosphine palladium were added, and the mixture was stirred at 120°C for 1.5 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated, and the resulting residue was dissolved in dimethyl sulfoxide. The residue was purified by basic HPLC preparative separation (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60), and then purified again by silica gel chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 90 / 10) to obtain 13 mg (yield 15%) of the title compound as a colorless powder. MS (ESI) m / z: 457 [M+H] ＋

[0273] Example 333 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-5-oxo-2,3-dihydropyrido[3,2-f][1,4]oxazepine-7-carbonitrile

[0274] A 20 mL recovery flask was charged with 50.0 mg of (3R)-7-bromo-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one, 16 mg of [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex, and 5.3 mg of zinc, followed by the addition of 1 mL of dimethylformamide. 58 mg of zinc cyanide was added to the reaction mixture, which was then heated and stirred at 140°C for 20 hours. The reaction mixture was returned to room temperature, and saturated aqueous sodium bicarbonate and ethyl acetate were added, followed by phase separation. The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in dimethyl sulfoxide and purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to obtain 8.3 mg (yield 19%) of the title compound as a pale yellow powder. MS (ESI) m / z: 457 [M+H] ＋

[0275] Example 334: The corresponding starting compounds were treated in the same manner as in Example 333 to give the compounds listed in Table 25 below.

[0276] Example 335 Preparation of (3R)-8-acetyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one

[0277] 120 mg of (3R)-8-bromo-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one, 0.119 mL of tributyl(1-ethoxyvinyl)tin, and 27 mg of tetrakistriphenylphosphinepalladium were dissolved in 3 mL of 1,4-dioxane and stirred at 100°C for 9 hours. After cooling to room temperature, 0.5 mL of 1 mol / L aqueous hydrochloric acid was added to the reaction solution and stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dimethyl sulfoxide and purified by reverse phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to give 26 mg (yield 23%) of the title compound as a yellow powder. MS (ESI) m / z: 474 [M+H] ＋

[0278] Example 336: The corresponding starting compounds were treated in the same manner as in Example 335 to give the compounds listed in Table 26 below.

[0279] Example 337 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one

[0280] (1) 150 mg of (3R)-8-bromo-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one, 88 mg of sodium iodide, and 84 mg of trans-N,N'-dimethylcyclohexane-1,2-diamine were suspended in 3 mL of 1,4-dioxane, and 5.6 mg of copper iodide was added. The reaction mixture was stirred at 110°C for 1.5 hours. The reaction mixture was returned to room temperature, diluted with ethyl acetate, and insoluble matter was removed by filtration. The filtrate was washed with 1 mol / L aqueous hydrochloric acid. The organic layer was separated, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 70 / 30 to 20 / 80) to obtain 42 mg (yield 26%) of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-8-iodo-3-methyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one as a colorless powder. MS (ESI) m / z: 558 [M+H] ＋(2) 40 mg of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-8-iodo-3-methyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one obtained in (1) above was dissolved in 2 mL of N,N-dimethylformamide, and 69 mg of methyl 2,2-difluoro-2-(fluorosulfonyl)acetate and 41 mg of copper iodide were added and stirred at 110 ° C. for 1 hour. 138 mg of methyl 2,2-difluoro-2-(fluorosulfonyl)acetate and 82 mg of copper iodide were added to the reaction solution and stirred at 110 ° C. for 3 hours. 138 mg of methyl 2,2-difluoro-2-(fluorosulfonyl)acetate and 82 mg of copper iodide were further added to the reaction solution and stirred at 110 ° C. for 3 hours. The reaction mixture was returned to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 70 / 30 to 25 / 75) to give 17 mg (yield 47%) of the title compound as a colorless powder. MS (ESI) m / z: 500 [M+H] ＋

[0281] Example 338 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydro-1H-pyrido[3,2-e][1,4]diazepin-5-one

[0282] 280 mg of tert-butyl (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-5-oxo-2,3-dihydropyrido[3,2-e][1,4]diazepine-1-carboxylate was dissolved in 3 mL of dichloromethane, and 107 μL of trimethylsilyl trifluoromethanesulfonate was added. The mixture was stirred at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in methanol, and saturated aqueous sodium bicarbonate was added and stirred for 5 minutes. Chloroform was added to the reaction mixture and stirred, after which the organic layer was separated using a Phase-Separator® and concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (solvent: ethyl acetate / methanol = 97 / 3 to 90 / 10) to give 134 mg (yield 59%) of the title compound as a colorless powder. MS (ESI) m / z: 431 [M+H] ＋

[0283] Example 339 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,7,8,9-tetrahydropyrido[3,2-c]azepine-2,5-dione and Example 340 Preparation of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-9-hydroxy-7-methyl-8,9-dihydro-7H-pyrido[3,2-c]azepin-5-one

[0284] 245 mg of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1-oxide-8,9-dihydro-7H-pyrido[3,2-c]azepin-1-ium-5-one was dissolved in 3 mL of acetic anhydride and stirred at 80°C for 1 hour. The reaction mixture was concentrated, and the resulting residue was dissolved in 3 mL of methanol, to which 91 mg of potassium carbonate was added, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The aqueous layer was extracted with chloroform. The organic layer was dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 80 / 20 to 20 / 80, then chloroform / methanol = 90 / 10) to obtain 90 mg (two-stage yield: 37%) of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,7,8,9-tetrahydropyrido[3,2-c]azepine-2,5-dione as a colorless powder. MS (ESI) m / z: 446 [M+H] ＋ At the same time, 135 mg of 6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-9-hydroxy-7-methyl-8,9-dihydro-7H-pyrido[3,2-c]azepin-5-one (diastereomer mixture ratio 65:35, two-stage yield 55%) was obtained as a colorless powder. MS (ESI) m / z: 446 [M+H] ＋

[0285] Example 341 Preparation of (7R)-3-(difluoromethyl)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydropyrazino[2,3-f][1,4]oxazepin-9-one

[0286] 150 mg of (7R)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6,7-dihydropyrazino[2,3-f][1,4]oxazepin-9-one was weighed into a 50 mL recovery flask and dissolved in 2.0 mL of dimethyl sulfoxide. Next, 0.80 mL of water, 250 mg of zinc bis(difluoromethanesulfinate), and 35 μL of trifluoroacetic acid were added. 250 μL of 70% aqueous tert-butyl hydroperoxide was then added and stirred at room temperature for 2 hours. The mixture was then heated and stirred at 50°C for 145 minutes. After cooling to room temperature, 226 mg of zinc bis(difluoromethanesulfinate) and 200 μL of 70% aqueous tert-butyl hydroperoxide were added, and the mixture was heated and stirred at 50°C for 4 hours. Aqueous sodium hydrogen sulfite, saturated ammonium chloride, saturated aqueous sodium hydrogen carbonate, and saturated saline were added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline and then dried over magnesium sulfate. After filtering off insoluble matter, the filtrate was concentrated under reduced pressure. 175 mg of the resulting pale yellow oil was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to obtain 37.3 mg (yield 21%) of a mixture of the title compound and (7R)-2-(difluoromethyl)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydropyrazino[2,3-f][1,4]oxazepin-9-one (content ratio 92:8) as a pale yellow amorphous solid. MS (ESI) m / z: 483 [M+H] ＋

[0287] Example 342 Preparation of (7R)-3-cyclopropyl-1-(difluoromethyl)-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepin-9-one

[0288] 125 mg of (7R)-3-cyclohexyl-8-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepin-9-one and 201 mg of zinc difluoromethanesulfinate were suspended in 2 mL of dimethyl sulfoxide, and 0.19 mL of tert-butyl hydroperoxide was added and stirred at 50°C for 3 hours. 201 mg of zinc difluoromethanesulfinate and 0.19 mL of tert-butyl hydroperoxide were added to the reaction solution, and the mixture was stirred at 50°C for 3 hours. The temperature was raised to 70°C and the mixture was stirred for 7 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: chloroform / methanol = 100 / 0 to 85 / 15) and then by reverse phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70) to give 7 mg (yield 5%) of the title compound as a colorless powder. MS (ESI) m / z: 509 [M+H] ＋

[0289] Example 343 Preparation of 2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-6-(trifluoromethyl)-3,4-dihydro-2,7-naphthyridin-1-one

[0290] 179 mg of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-amine was dissolved in 3 mL of ethanol, and 120 mg of ethyl 4-[(E)-prop-1-enyl]-6-(trifluoromethyl)pyridine-3-carboxylate was added. The mixture was stirred at 50°C for 4 hours. The temperature was raised to 90°C and the mixture was stirred for 1 hour. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in 2 mL of N-methylpyrrolidone and stirred at 130°C for 3.5 hours. After cooling to room temperature, an aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 67 / 33 to 33 / 67) to give 69.7 mg (yield 31%) of the title compound as a pale yellow powder. MS (ESI) m / z: 484 [M+H] ＋

[0291] Example 344 Preparation of 7-chloro-3-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2,2-dimethyl-pyrido[3,4-e][1,3]oxazin-4-one

[0292] 121 mg of (3R)-8-chloro-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one was weighed into a 20 mL recovery flask, and 2.0 mL of N,N-dimethylformamide and 100 μL of ethanol were added. 21.8 mg of sodium hydride (60%) was added under ice cooling and stirred for 50 minutes under ice cooling. Saturated aqueous ammonium chloride and saturated saline were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate. After filtering off insoluble matter, the solution was concentrated under reduced pressure. 177 mg of the resulting colorless oil was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 65 / 35 to 35 / 65) to give 11.6 mg (10% yield) of the title compound as a colorless powder. MS (ESI) m / z: 466 / 468 [M+H] ＋

[0293] Example 345 Preparation of (3R)-2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-6-(trifluoromethyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one

[0294] (1) 20 mg of 1-[(2R)-2-(tert-butoxycarbonylamino)propyl]-5-(trifluoromethyl)pyrrole-2-carboxylate was dissolved in 1 mL of dichloromethane, and 12.2 mg of trimethylsilyl trifluoromethanesulfonate was added and stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain a crude product of 1-[(2R)-2-aminopropyl]-5-(trifluoromethyl)pyrrole-2-carboxylate ethyl trifluoromethanesulfonate. (2) 17.7 mg of the crude product of 1-[(2R)-2-aminopropyl]-5-(trifluoromethyl)pyrrole-2-carboxylate ethyl trifluoromethanesulfonate obtained in (1) above, 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-one, was dissolved in 1 mL of dichloromethane, and 9.2 μL of triethylamine was added. To this was added 17.5 mg of sodium triacetoxyborohydride and 3.8 μL of acetic acid, followed by stirring at room temperature for 3 hours. Saturated aqueous sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in 1 mL of ethanol and stirred at 100°C for 2 hours. The reaction mixture was returned to room temperature, diluted with dimethyl sulfoxide, and purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70) to obtain 13 mg (yield 50%) of the title compound as a colorless powder. MS (ESI) m / z: 472 [M+H] ＋

[0295] Example 346 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydro-1H-pyrido[2,3-e][1,4]diazepin-5-one

[0296] 82.1 mg of t-butyl (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-5-oxo-8-(trifluoromethyl)-2,3-dihydropyrido[2,3-e][1,4]diazepine-1-carboxylate was placed in a 10 mL recovery flask and dissolved in 1 mL of dichloromethane. 0.030 mL of trimethylsilyltrifluoromethanesulfonate was added at room temperature and stirred for 1 hour. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel chromatography (solvent: hexane / ethyl acetate = 90 / 10 to 30 / 70) to afford 51.0 mg (76% yield) of the title compound as a colorless powder. MS (ESI) m / z: 499 [M+H] ＋

[0297] Example 347 The corresponding starting compounds were treated in the same manner as in Example 170 to give the compounds listed in Table 27 below.

[0298] Examples 348 to 365: The racemic mixtures or diastereomeric mixtures prepared in the respective Examples above were separated by chiral high performance liquid chromatography (chiral HPLC) or chiral supercritical fluid chromatography (chiral SFC) to give the compounds listed in Table 28 below.

[0299] Examples 366 to 368: The corresponding starting compounds were treated in the same manner as in Example 1 to give the compounds listed in Table 29 below.

[0300] Example 369 Preparation of (7R)-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-2-propan-2-yloxy-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one 80 mg of (7R)-2-chloro-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one was dissolved in 1.7 mL of N,N-dimethylformamide, and 26.2 μL of 2-propanol and 13.7 mg of sodium hydride (60%) were added under ice cooling, followed by stirring at room temperature for 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 60 / 40 to 20 / 80) to obtain 34 mg (40% yield) of (7R)-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-2-propan-2-yloxy-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one as a colorless powder. MS (ESI) m / z: 491 [M+H] ＋

[0301] Examples 370 to 379: The corresponding starting compounds were treated in the same manner as in Example 369 to give the compounds listed in Table 30 below.

[0302] Examples 380 to 412: The corresponding starting compounds were treated in the same manner as in Example 168 to give the compounds listed in Table 31 below.

[0303] Example 413 The corresponding starting compounds were treated in the same manner as in Example 70 to give the compounds listed in Table 32 below.

[0304] Example 414 Preparation of 2-methoxy-N-[2-(3-methylphenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-propylpyridine-3-carboxamide

[0305] To a mixture of 50 mg of N-(2-azaspiro[3.3]heptan-6-yl)-2-methoxy-N-propylpyridine-3-carboxamide in 1.5 mL of methylene chloride, 0.0376 mL of 3-methylbenzenesulfonyl chloride and 0.072 mL of triethylamine were added and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, diluted with methanol, neutralized with 1 M hydrochloric acid, and purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70) to obtain 51.4 mg (yield 67.1%) of the title compound as a colorless viscous liquid. MS (ESI) m / z: 444 [M+H] ＋

[0306] Examples 415 to 421 The corresponding starting compounds were treated in the same manner as in Example 414 to give the compounds listed in Table 33 below.

[0307] Example 422 The corresponding starting compounds were treated in the same manner as in Example 45 to give the compounds listed in Table 34 below.

[0308] Example 423 Preparation of N-[2-(benzenesulfonyl)-2-azaspiro[3.3]heptan-6-yl]-2-methoxy-N-propylpyridine-3-carboxamide

[0309] To a mixture of 74.8 mg of 2-(benzenesulfonyl)-N-propyl-2-azaspiro[3.3]heptan-6-amine and 55.0 mg of 2-methoxypyridine-3-carboxylic acid in 1.0 mL of N,N-dimethylformamide, 133 mg of HATU and 150 μL of diisopropylethylamine were added and stirred at room temperature for 1 hour and 45 minutes. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was extracted with ethyl acetate and the organic layer was concentrated. The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70) to afford 94.6 mg (87% yield) of the title compound as a colorless oil. MS (ESI) m / z: 430 [M+H] ＋

[0310] Examples 424 to 431 The corresponding starting compounds were treated in the same manner as in Example 423 to give the compounds listed in Table 35 below.

[0311] Example 432 Preparation of 1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,3-diazepan-2-one

[0312] To a solution of 30 mg of 4-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]pentane-1,4-diamine in 0.42 mL of N,N-dimethylformamide, 0.044 mL of diisopropylethylamine and 15.1 mg of carbonyldiimidazole were added and stirred at room temperature for 1 hour. After stirring at room temperature for 30 minutes, 9.6 mg of carbonyldiimidazole was added to the reaction mixture, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, then separated using a Phase-Separator® and concentrated under reduced pressure. The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 80 / 20 to 50 / 50) to afford 5.3 mg (16% yield) of the title compound as a colorless powder. MS (ESI) m / z: 382 [M+H] ＋

[0313] Example 433 Preparation of 3-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-4-methyl-1,3-oxazinan-2-one

[0314] (1) To a mixture of 100 mg of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-amine and 48.9 mg of 4-hydroxy-2-butanone in 1.85 mL of methylene chloride, 0.021 mL of acetic acid and 133.3 mg of sodium triacetoxyborohydride were added and stirred at room temperature for 1 hour. After adding saturated aqueous sodium bicarbonate to the reaction mixture and stirring, the organic layer was separated using a Phase-Separator® and concentrated under reduced pressure to obtain the crude product 3-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]butan-1-ol. (2) To a 1.85 mL methylene chloride solution of the crude 3-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]butan-1-ol obtained in (1) above, 0.154 mL triethylamine and 120 mg carbonyldiimidazole were added, and the mixture was stirred at room temperature for 1 hour. 9.0 mg dimethylaminopyridine was then added, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 98 / 2) to afford 115 mg of the title compound (2-stage yield 78%) as a colorless oil. MS (ESI) m / z: 369 [M+H] ＋

[0315] Example 434 Preparation of 1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-1,3-diazinan-2-one

[0316] To a mixture of 250 mg of benzyl N-[3-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]butyl]carbamate, 133 mg of carbonyldiimidazole, and 0.20 mL of triethylamine in 2.4 mL of tetrahydrofuran, 50 mg of 10% palladium on carbon was added and stirred at room temperature for 1 hour and 30 minutes under a hydrogen atmosphere. After purging the reaction system with nitrogen, 133 mg of carbonyldiimidazole and 0.20 mL of triethylamine were added and stirred at room temperature for 1 hour. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. 3.2 mL of methylene chloride and 0.067 mL of triethylamine were added to the resulting residue, and the mixture was stirred at room temperature for 1 hour and then allowed to stand for 2 days. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 80 / 20 to 50 / 50) to give 155 mg (yield 87%) of the title compound as a colorless powder. MS (ESI) m / z: 368 [M+H] ＋

[0317] Example 435 Preparation of (5R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methylimidazolidin-2-one

[0318] (1) 20 mg of 10% palladium on carbon was added to a mixture of 200 mg of benzyl N-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propyl]carbamate in tetrahydrofuran, and the mixture was stirred at room temperature under a hydrogen atmosphere for 1 hour. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure to obtain a crude product of (2R)-N2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]propane-1,2-diamine. (2) To the crude product of (2R)-N2-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]propane-1,2-diamine obtained in (1) above, 4.3 mL of methylene chloride, 0.18 mL of triethylamine, and 140 mg of carbonyldiimidazole were added, and the mixture was stirred at room temperature for 2 hours. 2.6 mg of dimethylaminopyridine was added to the reaction mixture, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 95 / 5) to give 122 mg (yield 76%) of the title compound as a colorless viscous material. MS (ESI) m / z: 354 [M+H] ＋

[0319] Example 436 (4R*,7S*)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-4,7-dimethylazepan-2-one and Example 437 Preparation of (4R*,7R*)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-4,7-dimethylazepan-2-one

[0320] (1) To a mixture of 100 mg of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-amine, 87.8 mg of 3-methyl-6-oxoheptanoic acid, and 1.85 mL of methylene chloride, 0.021 mL of acetic acid and 133.3 mg of sodium triacetoxyborohydride were added and stirred at room temperature for 1 hour. Methanol was added to the reaction mixture, which was then stirred and concentrated under reduced pressure. The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 90 / 10 to 60 / 40) to obtain a diastereomeric mixture of 6-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]-3-methyl-heptanoic acid. (2) The diastereomeric mixture of 6-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]-3-methyl-heptanoic acid obtained in (1) above was treated in the same manner as in Example 423, and the diastereomers were separated to obtain the title compound.

[0321] Example 436 (4R*,7S*)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-4,7-dimethylazepan-2-one 40 mg (two-step yield 39%) MS (ESI) m / z: 395 [M + H] ＋

[0322] Example 437 (4R*,7R*)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-4,7-dimethylazepan-2-one 47.3 mg (two-step yield 46%) MS (ESI) m / z: 395 [M + H] ＋

[0323] Examples 438 to 439 The corresponding starting compounds were treated in the same manner as in Examples 436 and 437 to give the compounds listed in Table 36 below.

[0324] Example 440 Preparation of 1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methylpiperidin-2-one

[0325] To a mixture of 161 mg of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-amine and 3.0 mL of acetonitrile, 0.15 mL of ethyl 5-oxohexanoate, 190 mg of sodium triacetoxyborohydride, and 0.025 mL of acetic acid were added and stirred at room temperature for 16 hours and 30 minutes. The reaction mixture was further heated under reflux overnight. The reaction mixture was returned to room temperature, and ethyl acetate was added. The organic phase was washed sequentially with saturated aqueous sodium bicarbonate and saturated brine. The organic phase was dried over magnesium sulfate, and insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to afford 120 mg (yield 55%) of the title compound as a colorless oil. MS (ESI) m / z: 367 [M+H] ＋

[0326] Example 441 Preparation of 4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methylthiomorpholin-3-one

[0327] (1) To a mixture of 430 mg of ethyl 2-[2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propylsulfanyl]acetate, 2.0 mL of tetrahydrofuran, and 2.0 mL of ethanol, 1.5 mL of 1M aqueous sodium hydroxide was added and the mixture was stirred at room temperature overnight. 1.5 mL of 1M hydrochloric acid was added to the reaction mixture, and the mixture was concentrated under reduced pressure to obtain a crude product of 2-[2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propylsulfanyl]acetic acid. (2) The crude product obtained in (1) above was treated in the same manner as in Example 423 to obtain 352 mg (yield 92%) of the title compound as a colorless viscous liquid. MS (ESI) m / z: 385 [M+H] ＋

[0328] Example 442 Preparation of (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,4-diazepan-2-one

[0329] To a mixture of 1.39 g of tert-butyl (5R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methyl-3-oxo-1,4-diazepane-1-carboxylate and 13.4 mL of methylene chloride, 0.55 mL of trimethylsilyl trifluoromethanesulfonate was added and stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and then saturated aqueous sodium bicarbonate and chloroform were added to the residue and stirred. The organic layer was separated using a Phase-Separator® and concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 90 / 10) to afford 729 mg (71% yield) of the title compound as a colorless powder. MS (ESI) m / z: 382 [M+H] ＋

[0330] Example 443 Preparation of (7R)-4-(cyclopropylmethyl)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,4-diazepan-2-one

[0331] A mixture of 15 mg of (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,4-diazepan-2-one, 3.58 mg of cyclopropanecarboxaldehyde, 2.3 μL of acetic acid, and 0.2 mL of methylene chloride was stirred at room temperature for 10 minutes, followed by the addition of 12.5 mg of sodium triacetoxyborohydride and stirring at room temperature for 2 hours. After adding 1 mL of methylene chloride and 1 mL of saturated aqueous sodium bicarbonate to the reaction mixture and stirring, the organic phase was separated using a Phase-Separator® and concentrated. The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to give 12.5 mg of the title compound (73% yield). MS (ESI) m / z: 436 [M+H] ＋

[0332] Examples 444 to 448 The corresponding starting compounds were treated in the same manner as in Example 443 to give the compounds listed in Table 37 below.

[0333] Examples 449 to 454 (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,4-diazepan-2-one and a corresponding reagent were used in the same manner as in Example 423 to give the compounds listed in Table 38 below.

[0334] Example 455 Preparation of (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-4-methylsulfonyl-1,4-diazepan-2-one

[0335] To a mixture of 15 mg of (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,4-diazepan-2-one, 0.02 mL of diisopropylethylamine, and 0.4 mL of methylene chloride, 13.7 mg of methanesulfonic anhydride was added and stirred at room temperature for 30 minutes. Water and chloroform were added to the reaction mixture, and the mixture was stirred. The organic layer was separated using a Phase-separator® and concentrated under reduced pressure. The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to afford 17.4 mg (96% yield) of the title compound as a colorless powder. MS (ESI) m / z: 460 [M+H] ＋

[0336] Example 456 Preparation of (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-4-pyridin-2-yl-1,4-diazepan-2-one

[0337] To a mixture of 1.8 mg of tris(dibenzylideneacetone)dipalladium, 1.7 mg of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride, 6.6 mg of sodium t-butoxide, and 1 mL of 1,4-dioxane, 15 mg of (7R)-1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-1,4-diazepan-2-one and 18.6 mg of 2-bromopyridine were added, and the mixture was stirred at room temperature for 3 hours and then heated to reflux for 4 hours. 18.6 mg of 2-bromopyridine, 1.8 mg of tris(dibenzylideneacetone)dipalladium, and 1.7 mg of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride were added, and the mixture was heated to reflux for 3 hours. The reaction mixture was returned to room temperature, and water and chloroform were added and stirred. The organic layer was separated using a Phase-Separator® and concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (solvent: hexane / ethyl acetate = 100 / 0 to 0 / 100) and then purified again by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 60 / 40 to 30 / 70) to obtain 7.5 mg (42% yield) of the title compound as a colorless powder. MS (ESI) m / z: 459 [M+H] ＋

[0338] Example 457 Preparation of 4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methyl-1,4-oxazepan-3-one

[0339] To a mixture of 80 mg of 2-chloro-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-(4-hydroxybutan-2-yl)acetamide and 0.95 mL of N,N-dimethylformamide, 8.4 mg of sodium hydride (60%) was added under ice-cooling, and the mixture was stirred for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, and the organic layer was separated using a Phase-Separator® and concentrated under reduced pressure. The resulting residue was purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to give 2.6 mg (yield 3.6%) of the title compound as a pale yellow viscous material. MS (ESI) m / z: 383 [M+H] ＋

[0340] Example 458 Preparation of (5R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-5-methylmorpholin-3-one

[0341] To a mixture of 50 mg of (2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propan-1-ol, 75 μL of triethylamine, and 1.5 mL of tetrahydrofuran, 38 μL of 2-chloroacetyl chloride was added dropwise and stirred for 1 hour and 20 minutes. 90 μL of 28% sodium methoxide methanol solution was added to the reaction mixture, and after stirring for 2 hours, 50 μL of 28% sodium methoxide methanol solution was added and stirred overnight. 50 μL of 28% sodium methoxide methanol solution was added again and stirred for 4 hours. Water was added to the reaction mixture, neutralized with 1 M hydrochloric acid, and chloroform was added and stirred. The organic layer was separated using a Phase-separator® and concentrated under reduced pressure. The resulting residue was purified by reverse phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 80 / 20 to 50 / 50) to give 29.4 mg (yield 52%) of the title compound as a yellow solid. MS (ESI) m / z: 369 [M+H] ＋

[0342] Example 459 Preparation of 1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methylazepan-2-one

[0343] The title compound was obtained using 1-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-methyl-3,4-dihydro-2H-azepin-7-one in the same manner as in Example 85. MS (ESI) m / z: 381 [M+H] ＋

[0344] Example 460 Preparation of (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-1,4-oxazepan-5-one

[0345] tert-Butyl 3-[(2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propoxy]propanoate was treated in the same manner as in Example 442 and Example 423 to obtain the title compound. MS (ESI) m / z: 383 [M+H] ＋

[0346] In producing the compounds of the above examples, commercially available reagents or compounds chemically modified from such reagents by existing methods or methods equivalent thereto can be used as raw materials and intermediates. Alternatively, the compounds can be produced using the compounds described in the following Reference Examples.

[0347] Reference Example 1 Preparation of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3,3]heptan-6-one

[0348] 27.0 g of tert-butyl 6-oxo-2-azaspiro[3.3]-heptane-2-carboxylate was dissolved in 250 mL of dichloromethane, and 24.7 mL of trimethylsilyl trifluoromethanesulfonate was added dropwise over 5 minutes under ice-cooling. The mixture was warmed to room temperature and stirred for 0.5 hours (Reaction Solution 1). 24.9 g of 2-fluorobenzenesulfonyl chloride was dissolved in 250 mL of dichloromethane, and 35.5 mL of triethylamine was added under ice-cooling. The above-mentioned Reaction Solution 1 was added dropwise thereto over 10 minutes. The mixture was then warmed to room temperature and stirred for 1 hour. The reaction solution was concentrated to reduce the solvent volume to half. The organic layer was washed twice with 1N aqueous sodium hydroxide solution, followed by two washes with 1N hydrochloric acid. The organic layer was then washed once with 1N aqueous sodium hydroxide solution. The organic layer was washed with saturated saline, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was washed by suspension in hexane / ethyl acetate, and the solid was collected by filtration and dried under reduced pressure to obtain 24.8 g (yield 72%) of the title compound as a brown powder. MS (ESI) m / z: 270 [M+H] ＋

[0349] Reference Example 2 Preparation of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-amine

[0350] (1) 3.17 g of tert-butyl 6-amino-2-azaspiro[3.3]heptane-2-carboxylate was weighed into a 200 mL recovery flask, and 50 mL of dichloromethane and 3.5 mL of triethylamine were added, followed by stirring under ice cooling. Next, 4.03 g of 2-nitrobenzenesulfonyl chloride was added, followed by stirring at room temperature for 15 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution, and the mixture was stirred at room temperature for 5 minutes. A 1:1 mixed solvent of ethyl acetate and hexane and saturated saline were added to the reaction solution, and the organic layer was extracted. The aqueous layer was again extracted with a 1:1 mixed solvent of ethyl acetate and hexane, and the organic layers were mixed. The combined organic layers were washed with saturated saline and then dried over magnesium sulfate. After filtering off insoluble matter, the filtrate was concentrated under reduced pressure. 5.66 g of the resulting colorless solid was suspended in 60 mL of a 1:5 mixed solvent of ethyl acetate and hexane, and the solid was collected by filtration and dried under reduced pressure to obtain 5.45 g (92% yield) of tert-butyl 6-[(2-nitrophenyl)sulfonylamino]-2-azaspiro[3.3]heptane-2-carboxylate as a colorless powder. MS (ESI) m / z: 396 [M-H] － (2) 5.45 g of tert-butyl 6-[(2-nitrophenyl)sulfonylamino]-2-azaspiro[3.3]heptane-2-carboxylate obtained in (1) above was weighed into a 200 mL recovery flask, 45 mL of dichloromethane was added, and the mixture was stirred under ice cooling. Next, 3.4 mL of trimethylsilyl trifluoromethanesulfonate was added, followed by stirring at room temperature for 80 minutes. The reaction solution was concentrated under reduced pressure to obtain 8.07 g (88% yield) of N-(2-azaspiro[3.3]heptan-6-yl)-2-nitro-benzenesulfonamide trifluoromethanesulfonate as a colorless amorphous solid. MS (ESI) m / z: 298 [M+H] ＋(3) 8.07 g of N-(2-azaspiro[3.3]heptan-6-yl)-2-nitro-benzenesulfonamide trifluoromethanesulfonate obtained in (2) above was weighed into a 200 mL recovery flask, and 60 mL of methylene chloride and 5.0 mL of triethylamine were added. The mixture was stirred under ice cooling. Next, 3.19 g of 2-fluorobenzenesulfonyl chloride was added, and the mixture was stirred under ice cooling for 105 minutes. Subsequently, 2.5 mL of triethylamine and 0.50 g of 2-fluorobenzenesulfonyl chloride were added, and the mixture was stirred at room temperature for 15 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution, and the mixture was extracted with a 1:1 ethyl acetate:hexane mixed solvent. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated brine, and then dried over magnesium sulfate. After filtering off insoluble matter, the filtrate was concentrated under reduced pressure. The resulting brown solid (7.33 g) was suspended in 25 mL of chloroform, and the solid was collected by filtration, washed with 5 mL of chloroform, and then dried under reduced pressure to give 2.54 g of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-nitro-benzenesulfonamide as a colorless powder. The mother liquor after filtration was concentrated under reduced pressure, and the resulting brown solid was suspended in 6 mL of chloroform. The solid was collected by filtration, washed with 4 mL of chloroform, and then dried under reduced pressure to give 1.57 g of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-nitro-benzenesulfonamide as a colorless powder. The mother liquor after filtration was concentrated under reduced pressure, and 3.15 g of the resulting brown oil was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 50 / 50 to 15 / 85) to give 1.72 g of a pale yellow solid. This was suspended in 12 mL of a 1:1 mixed solvent of chloroform and hexane, and the solid was collected by filtration, washed with hexane, and dried under reduced pressure to obtain 1.39 g of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-nitro-benzenesulfonamide as a colorless solid. The total amount of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-nitro-benzenesulfonamide obtained was 5.49 g. MS (ESI) m / z: 456 [M+H] ＋(4) 1.38 g of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2-nitro-benzenesulfonamide obtained in (3) above was weighed into a 100 mL recovery flask, and 17 mL of acetonitrile was added. Next, 1.48 g of cesium carbonate and 500 μL of 4-ethylthiophenol were added and stirred at room temperature for 80 minutes. An additional 200 μL of 4-ethylthiophenol was then added, and the mixture was stirred at room temperature for 4 hours. Water and 15 mL of 1 mol / L hydrochloric acid were added to the reaction solution to adjust the pH to 2. Hexane was added to the mixture, and the aqueous layer was extracted. Water was added again to the organic layer, and the aqueous layer was extracted. The combined aqueous layers were adjusted to pH 9 with 16 mL of 1 mol / L aqueous sodium hydroxide and saturated aqueous sodium bicarbonate, and then extracted with chloroform (100 mL x 2). The organic layer was dried over sodium sulfate, the insoluble matter was filtered off, and the solution was concentrated under reduced pressure to give 770 mg (yield 94%) of the title compound as a yellow oil. MS (ESI) m / z: 271 [M+H] ＋

[0351] Reference Example 3 Preparation of (2R)-2-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propan-1-ol

[0352] 24.8 g of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-one was dissolved in 300 mL of dichloromethane, and 8.98 g of (2R)-2-aminopropan-1-ol and 5.26 mL of acetic acid were added. Under ice cooling, 39.0 g of sodium triacetoxyborohydride was slowly added in four portions. The mixture was warmed to room temperature and stirred for 3 hours. 1N aqueous sodium hydroxide solution was added to the reaction mixture, which was then extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. (Crude Product 1). Meanwhile, the aqueous layer was saturated with sodium chloride and extracted three times with chloroform. The combined organic layers were washed with saturated brine, dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain 5.37 g (18% yield) of the title compound as a pale yellow powder. These crystals were added to crude product 1 for crystallization, and the resulting solid was washed by suspension with hexane / ethyl acetate. The resulting solid was collected by filtration and dried under reduced pressure to obtain 17.2 g (yield 57%) of the title compound as a white powder. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (solvent: ethyl acetate / methanol = 100 / 0 to 92 / 8). The collected fractions were concentrated under reduced pressure, and the resulting residue was washed by suspension with hexane / ethyl acetate. The solid was collected by filtration and dried under reduced pressure to obtain 3.66 g (yield 12%) of the title compound as a white powder. MS (ESI) m / z: 329 [M+H] ＋

[0353] Reference Examples 4 to 27: The corresponding starting compounds were treated in the same manner as in Reference Example 3 to give the compounds listed in Table 39 below.

[0354] Reference Example 28 Preparation of tert-butyl 6-(7-methyl-5-oxo-7,8-dihydro-1,6-naphthyridin-6-yl)-2-azaspiro[3.3]heptane-2-carboxylate

[0355] 180 mg of tert-butyl 6-amino-2-azaspiro[3.3]heptane-2-carboxylate, 155 mg of tert-butyl 2-acetonylpyridine-3-carboxylate (purity 39 mass%, containing 7-methylpyrano[4,3-b]pyridin-5-one as an impurity), and 0.1 mL of acetic acid were dissolved in 3 mL of dichloromethane, and 124 mg of sodium triacetoxyborohydride was added and stirred at room temperature for 20 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was dissolved in 3 mL of acetonitrile and stirred at 50°C for 1 hour. The temperature was raised to 80°C and the mixture was stirred for 11 hours. The reaction mixture was dissolved in dimethyl sulfoxide and purified by reverse phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 70 / 30 to 40 / 60) to obtain 22 mg (yield 21%) of the title compound as a brown powder. MS (ESI) m / z: 358 [M+H] ＋

[0356] Reference Example 29: Preparation of 1-[[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]amino]propan-2-ol

[0357] 300 mg of 2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-amine was dissolved in 1 mL of tetrahydrofuran, 155 μL of propylene oxide was added, and the mixture was stirred at room temperature for 15 hours. 466 μL of propylene oxide was added to the reaction solution, and the mixture was stirred at 60°C for 15 hours. 311 μL of propylene oxide was added to the reaction solution, and the mixture was stirred at 60°C for 2 hours. The reaction solution was dissolved in dimethyl sulfoxide and purified by reverse-phase HPLC (solvent: 10 mM aqueous ammonium carbonate / acetonitrile = 80 / 20 to 50 / 50) to obtain 168 mg (yield 46%) of the title compound as a colorless viscous compound. MS (ESI) m / z: 329 [M+H] ＋

[0358] Reference Examples 30-31: The corresponding starting materials were treated in the same manner as in Example 170 to give the compounds listed in Table 40 below.

[0359] Reference Examples 32 to 35: The corresponding starting materials were treated in the same manner as in Example 1 to give the compounds listed in Table 41 below.

[0360] Reference Examples 36 to 40: The corresponding starting materials were treated in the same manner as in Example 8 to give the compounds listed in Table 42 below.

[0361] Reference Examples 41-42: The corresponding starting materials were treated in the same manner as in Example 44 to give the compounds listed in Table 43 below.

[0362] Reference Example 43: Preparation of 4-(2-azaspiro[3.3]heptan-6-yl)-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one

[0363] 1.36 g of tert-butyl 6-(3-methyl-5-oxo-2,3-dihydropyrido[3,2-f][1,4]oxazepin-4-yl)-2-azaspiro[3.3]heptane-2-carboxylate was dissolved in 17 mL of dichloromethane, and 0.710 mL of trimethylsilyl trifluoromethanesulfonate was added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The resulting residue was suspended and washed with diethyl ether, the filtrate was removed, and the residue was dried under reduced pressure. This was dissolved in water, a saturated aqueous solution of sodium bicarbonate was added, and the mixture was stirred for 15 minutes. The mixture was then extracted with a mixed solution of chloroform and methanol. The organic layer was dried over magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure and dried to obtain 864 mg (yield 95%) of the title compound as a yellow oil. MS (ESI) m / z: 274 [M+H] ＋

[0364] Reference Example 44 Preparation of 3-bromo-N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-(1-methylallyl)-5-(trifluoromethyl)pyridine-2-carboxamide

[0365] (1) 410 mg of 3-bromo-5-(trifluoromethyl)pyridine-2-carboxylic acid was weighed into a 30 mL recovery flask and 6.0 mL of dichloromethane was added. This mixture was stirred under ice cooling, and 200 μL of oxalyl chloride and 10 μL of N,N-dimethylformamide were added, followed by stirring at room temperature for 50 minutes. The reaction mixture was concentrated under reduced pressure to obtain crude 3-bromo-5-(trifluoromethyl)pyridine-2-carboxylic acid chloride as a yellow oil. (2) 459 mg of 2-(2-fluorophenyl)sulfonyl-N-(1-methylallyl)-2-azaspiro[3.3]heptan-6-amine was weighed into a 10 mL recovery flask and 6.0 mL of dichloromethane and 800 μL of triethylamine were added, followed by stirring under ice cooling. To this was added a solution prepared by dissolving the entire amount of the crude 3-bromo-5-(trifluoromethyl)pyridine-2-carboxylic acid chloride obtained in (1) above in 4.0 mL of dichloromethane, and the mixture was stirred for 30 minutes under ice-cooling, and then for 30 minutes at room temperature. Saturated saline was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over magnesium sulfate. After filtering off insoluble matter, the solution was concentrated under reduced pressure. 0.84 g of the resulting orange oil was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 80 / 20 to 55 / 45) to obtain 707 mg (yield 87%) of the title compound as a colorless powder. MS (ESI) m / z: 576 / 578 [M+H] ＋

[0366] Reference Examples 45 to 52: The corresponding starting compounds were treated in the same manner as in Reference Example 44 to give the compounds listed in Table 44 below.

[0367] Reference Example 53 Preparation of N-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-N-(1-methylallyl)-2-(trifluoromethyl)-5-vinyl-thiazole-4-carboxamide

[0368] (1) 106 mg of ethyl 2-(trifluoromethyl)-5-vinyl-thiazole-4-carboxylate was dissolved in 3 mL of ethanol and 3 mL of tetrahydrofuran, and 0.842 mL of 1 mol / L aqueous sodium hydroxide was added and stirred at room temperature for 20 minutes. 1 mol / L aqueous sodium hydroxide was added to the reaction mixture, and back-extraction was performed with ethyl acetate-hexane. The organic layer was washed with 1 mol / L aqueous sodium hydroxide, and the combined aqueous layer was acidified with 6 mol / L aqueous hydrochloric acid and then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure to obtain 25.5 mg (yield 27%) of 2-(trifluoromethyl)-5-vinyl-thiazole-4-carboxylic acid as a white powder. (2) 25.5 mg of 2-(trifluoromethyl)-5-vinyl-thiazole-4-carboxylic acid obtained in (1) above was subjected to toluene azeotropy and then dissolved in 2 mL of dichloromethane. 24.2 μL of oxalyl chloride and 8 μL of N,N-dimethylformamide were added and the mixture was stirred for 20 minutes. The reaction mixture was concentrated under reduced pressure to obtain a crude product of 2-(trifluoromethyl)-5-vinyl-thiazole-4-carbonyl chloride. (3) The crude product of 2-(trifluoromethyl)-5-vinyl-thiazole-4-carbonyl chloride obtained in (2) above was dissolved in 3 mL of dichloromethane, and 46.3 mg of 2-(2-fluorophenyl)sulfonyl-N-(1-methylallyl)-2-azaspiro[3.3]heptan-6-amine and 79.4 μL of triethy...

Claims

1. The following formula [I]: [In the formula, ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aliphatic heterocyclic group, and R １ and R ２ each represent an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group which may contain a double bond in part of the ring, an optionally substituted amino group, an optionally substituted alkoxy group, or an optionally substituted alkylthio group, or R １ and R ２ together represent a group forming a ring], or a pharmaceutically acceptable salt thereof.

2. The compound of the formula [I] is a compound of the following formula [II]: [wherein ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group or an optionally substituted aliphatic heterocyclic group; ring B represents an optionally substituted aliphatic heterocyclic group which may contain a double bond as part of the ring; ring C represents an optionally substituted aryl group which may be partially hydrogenated, an optionally substituted heteroaryl group which may be partially hydrogenated, an optionally substituted cycloalkyl group or an optionally substituted aliphatic heterocyclic group], the compound according to claim 1 or a pharmacologically acceptable salt thereof.

3. In the group represented by the formula [II], each substituent of the optionally substituted aryl group, optionally substituted heteroaryl group, and optionally substituted aliphatic heterocyclic group represented by ring A is independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, an alkoxyalkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkanoyl group, an alkoxycarbonyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, a sulfonyl group optionally substituted with an alkyl group, an aminocarbonyl group optionally substituted with 1 to 2 alkyl groups, a nitro group, and an aryl group, and is 1 to 3 groups; the aryl moiety of the optionally substituted aryl group represented by ring A is a 6- to 10-membered monocyclic or bicyclic aryl; the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring A is a 5- to 10-membered monocyclic or bicyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; each substituent of the optionally substituted aliphatic heterocyclic group represented by ring B, which may contain a double bond in part of the ring; the optionally substituted aryl group represented by ring C, which may be partially hydrogenated; the optionally substituted heteroaryl group represented by ring C, which may be partially hydrogenated; the optionally substituted cycloalkyl group represented by ring C; and the optionally substituted aliphatic heterocyclic group represented by ring C; is independently selected from the group consisting of a halogen atom; a hydroxyl group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxyalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group; an alkylene group optionally substituted with 1 to 2 groups independently selected from a halogen atom; an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkylthio group; an aryl group;A cycloalkyl group which may be substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group which may be substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an alkanoyl group which may be substituted with 1 to 2 groups independently selected from the group consisting of a cycloalkyl group, an aryl group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkoxycarbonyl group which may be substituted with an aryl group, and which is 1 to 8 groups independently selected from the group consisting of these, wherein the aliphatic heterocyclic moiety of the aliphatic heterocyclic group represented by Ring B, which may be substituted and may contain a double bond in a part of the ring, is a 5- to 7-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aryl moiety of the aryl group represented by Ring C, which may be substituted and may be partially hydrogenated, is a 6- to 10-membered monocyclic or bicyclic aryl; the heteroaryl moiety of the heteroaryl group represented by Ring C, which may be substituted and may be partially hydrogenated, is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aliphatic heterocyclic moiety of the aliphatic heterocyclic group represented by Ring C, which may be substituted, is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; in each of the substituents of the group represented by Ring B or Ring C, the aryl group in the selected group is a 6- to 10-membered monocyclic or bicyclic aryl; and in each of the substituents of the group represented by Ring B or Ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the compound according to claim 2 or a pharmaceutically acceptable salt thereof.; 4. In the group represented by the formula [II], ring A is an aryl group which may be substituted or a heteroaryl group which may be substituted; the aryl moiety of the aryl group which may be substituted represented by ring A is a monocyclic or bicyclic aryl having 6 to 10 members; the heteroaryl moiety of the heteroaryl group which may be substituted represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; the aliphatic heterocyclic moiety of the aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring represented by ring B is a 5- to 7-membered monocyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; ring C is an aryl group which may be substituted and may be partially hydrogenated, a heteroaryl group which may be substituted and may be partially hydrogenated, a cycloalkyl group which may be substituted or an aliphatic heterocyclic group which may be substituted; the aryl moiety of the aryl group which may be substituted and may be partially hydrogenated represented by ring C is a monocyclic or bicyclic aryl having 6 to 10 members; the heteroaryl moiety of the heteroaryl group which may be substituted and may be partially hydrogenated represented by ring C is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; the aliphatic heterocyclic moiety of the aliphatic heterocyclic group which may be substituted represented by ring C is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, the compound or a pharmacologically acceptable salt thereof according to claim 2 or 3.

5. In the group represented by the formula [II], ring A is a phenyl group which may be substituted or a monocyclic heteroaryl group which may be substituted, each of the substituents of the phenyl group which may be substituted or the monocyclic heteroaryl group which may be substituted represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group and a nitro group, the heteroaryl moiety of the monocyclic heteroaryl group which may be substituted represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, the substituents of the aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring represented by ring B are a halogen atom; a hydroxyl group; an oxo group; an alkyl group; a haloalkyl group; an alkoxyalkyl group; an alkoxy group; an alkylene group which may be substituted by 1 to 2 groups independently selected from a halogen atom; a cycloalkyl group; an alkanoyl group which may be substituted by 1 to 2 groups independently selected from the group consisting of a cycloalkyl group, an aryl group and an alkoxy group; and an alkoxycarbonyl group which may be substituted by an aryl group, and are 1 to 4 groups independently selected from the group consisting of these, the aliphatic heterocyclic moiety of the aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring represented by ring B is a 5- to 7-membered monocyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, in the substituents of the group represented by ring B, the aryl group in the selected group is phenyl, ring C is a phenyl group which may be substituted, a monocyclic heteroaryl group which may be substituted and may be partially hydrogenated, a monocyclic cycloalkyl group which may be substituted or a monocyclic aliphatic heterocyclic group which may be substituted, and each of the substituents of the phenyl group which may be substituted; the monocyclic heteroaryl group which may be substituted and may be partially hydrogenated; the monocyclic cycloalkyl group which may be substituted; or the monocyclic aliphatic heterocyclic group which may be substituted; represented by ring C is a halogen atom; a hydroxyl group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group which may be substituted by a cyano group; a haloalkoxy group; an alkylene group;An amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkanoyl group, wherein the heteroaryl moiety of the optionally substituted and optionally partially hydrogenated monocyclic heteroaryl group represented by Ring C is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the aliphatic heterocyclic moiety of the optionally substituted monocyclic aliphatic heterocyclic group represented by Ring C is a 4- to 7-membered monocyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, in each of the substituents of the group represented by Ring C, the aryl group in the selected group is phenyl, and in each of the substituents of the group represented by Ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is a 4- to 9-membered monocyclic or bicyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, a compound according to any one of claims 2 to 4 or a pharmaceutically acceptable salt thereof.; 6. In the group represented by the formula [II], ring A is a phenyl group which may be substituted or a monocyclic heteroaryl group which may be substituted, and each of the substituents of the phenyl group which may be substituted or the monocyclic heteroaryl group which may be substituted represented by ring A is one or two groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group and a nitro group. The heteroaryl moiety of the monocyclic heteroaryl group which may be substituted represented by ring A is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl or triazinyl. The substituents of the aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring represented by ring B are a halogen atom; a hydroxyl group; an oxo group; an alkyl group; a haloalkyl group; an alkoxyalkyl group; an alkoxy group; an alkylene group which may be substituted by one or two groups independently selected from a halogen atom; a cycloalkyl group; an alkanoyl group which may be substituted by one or two groups independently selected from the group consisting of a cycloalkyl group, an aryl group and an alkoxy group; and an alkoxycarbonyl group which may be substituted by an aryl group, and are one to four groups independently selected from the group. The aliphatic heterocyclic moiety of the aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring represented by ring B is azolidinyl, diazolidinyl, azinanyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, diazepanyl or thiazepanyl. In the substituents of the group represented by ring B, the aryl group in the selected groups is phenyl. Ring C is a phenyl group which may be substituted, a monocyclic heteroaryl group which may be substituted and may be partially hydrogenated, a monocyclic cycloalkyl group which may be substituted or a monocyclic aliphatic heterocyclic group which may be substituted, and each of the substituents of the phenyl group which may be substituted; the monocyclic heteroaryl group which may be substituted and may be partially hydrogenated; the monocyclic cycloalkyl group which may be substituted; or the monocyclic aliphatic heterocyclic group which may be substituted; represented by ring C is a halogen atom;Amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of a salicylic acid group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group; an alkylene group; an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; an alkylthio group; an aryl group; a cycloalkyl group optionally substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group;and is a group of 1 to 4 independently selected from the group consisting of an alkanoyl group, wherein the heteroaryl moiety of the monocyclic heteroaryl group which may be substituted and may be partially hydrogenated represented by ring C is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl or triazinyl, the aliphatic heterocyclic moiety of the monocyclic aliphatic heterocyclic group which may be substituted represented by ring C is azetidinyl, oxetanyl, oxolanyl, azolidinyl, thiolanyl, oxazolidinyl, diazolidinyl, thiazolidinyl, oxanyl, azinanyl, dioxanyl, oxazinanyl, diazinanyl, thiazinanyl, thianyl, oxepanyl, azepanyl, thiepanyl, oxazepanyl, diazepanyl or thiazepanyl, in each of the substituents of the group represented by ring C, the aryl group in the selected group is phenyl, in each of the substituents of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is azetidinyl, oxetanyl, oxolanyl, azolidinyl, thiolanyl, oxazolidinyl, diazolidinyl, thiazolidinyl, oxanyl, azinanyl, dioxanyl, oxazinanyl, diazinanyl, thiazinanyl, thianyl, oxepanyl, azepanyl, thiepanyl, oxazepanyl, diazepanyl or thiazepanyl, or a ring in which two of the aliphatic heterocycles are condensed or bonded via a spiro atom, the compound according to any one of claims 2 to 5 or a pharmaceutically acceptable salt thereof.; 7. In the group represented by the formula [II], ring B is a 7-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring; ring C is a phenyl group which may be substituted, a 6-membered monocyclic heteroaryl group which may be substituted and may be partially hydrogenated or a 6-membered monocyclic aliphatic heterocyclic group which may be substituted, the compound or a pharmacologically acceptable salt thereof according to any one of claims 2 to 6.

8. In the group represented by the formula [II], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is one or two groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond in a part of the ring, the substituents of the optionally substituted 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may contain a double bond in a part of the ring are a halogen atom; an oxo group; an alkyl group; an alkoxyalkyl group; an alkylene group; a cycloalkyl group; an alkanoyl group optionally substituted with one or two groups independently selected from the group consisting of a cycloalkyl group, a phenyl group and an alkoxy group; and an alkoxycarbonyl group optionally substituted with an aryl group, and the aliphatic heterocyclic moiety of the optionally substituted 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may contain a double bond in a part of the ring is a 7-membered monocyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, ring C is an optionally substituted phenyl group, an optionally substituted and optionally partially hydrogenated 6-membered monocyclic heteroaryl group or an optionally substituted 6-membered monocyclic aliphatic heterocyclic group, each of the substituents of the optionally substituted phenyl group, the optionally substituted and optionally partially hydrogenated 6-membered monocyclic heteroaryl group or the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring C is a halogen atom; an oxo group; a cyano group; an alkyl group; a haloalkyl group; an alkoxy group; a cycloalkoxy group optionally substituted with a cyano group; a haloalkoxy group;An amino group optionally substituted with 1 to 2 groups independently selected from the group consisting of an alkyl group optionally substituted with a cycloalkyl group or an aryl group, an aryl group optionally substituted with a halogen atom, and a cycloalkyl group; a cycloalkyl group; an aliphatic heterocyclic group optionally substituted with 1 to 4 groups independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkylene group, and an alkoxy group; an aryloxy group; an aliphatic heterocyclic oxy group; and an alkanoyl group, wherein in each of the substituents of the group represented by ring C, the aryl group in the selected group is phenyl, and in each of the substituents of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is a 5- to 7-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, or a ring in which two such aliphatic heterocyclic rings are fused or bonded via a spiro atom, and the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, and the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring C is a 6-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the compound according to claim 7 or a pharmaceutically acceptable salt thereof.; 9. In the group represented by the formula [II], the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is thienyl or pyridyl; the aliphatic heterocyclic moiety of the optionally substituted 7-membered monocyclic aliphatic heterocyclic group represented by ring B, which may contain a double bond as part of the ring, is azepanyl, oxazepanyl, diazepanyl or thiazepanyl; the aryl moiety of the aryl group in the substituent of the group represented by ring B is phenyl; the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C, which may be partially hydrogenated, is pyridyl, pyrazinyl or pyrimidinyl; the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring C is oxazinanyl; in each of the substituents of the group represented by ring C, the aryl group in the selected group is phenyl; and in each of the substituents of the group represented by ring C, the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group in the selected group is azolidinyl, azinanil, oxazinanyl, diazinanyl, azepanyl or oxazepanyl. The compound according to claim 7 or 8, or a pharmaceutically acceptable salt thereof.

10. In the group represented by the formula [II], ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond as part of the ring; and ring C is an optionally substituted 5-membered monocyclic heteroaryl group or an optionally substituted 5-membered monocyclic aliphatic heterocyclic group. The compound according to any one of claims 2 to 6, or a pharmaceutically acceptable salt thereof.

11. In the group represented by the formula [II], ring A is an optionally substituted phenyl group, the substituent of the optionally substituted phenyl group represented by ring A is a halogen atom, ring B is an optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond in a part of the ring, the substituent of the optionally substituted 7-membered monocyclic aliphatic heterocyclic group represented by ring B is an oxo group; an alkyl group; and 1 to 4 groups independently selected from the group consisting of an alkylene group which may be substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom, the aliphatic heterocyclic moiety of the optionally substituted 7-membered monocyclic aliphatic heterocyclic group represented by ring B which may contain a double bond in a part of the ring is a 7-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, ring C is an optionally substituted 5-membered monocyclic heteroaryl group or an optionally substituted 5-membered monocyclic aliphatic heterocyclic group, each of the substituents of the optionally substituted 5-membered monocyclic heteroaryl group or the optionally substituted 5-membered monocyclic aliphatic heterocyclic group represented by ring C is a halogen atom; an alkyl group; a haloalkyl group; an alkylene group; a cycloalkyl group which may be substituted with 1 to 2 groups independently selected from the group consisting of a halogen atom and a haloalkyl group; and 1 to 2 groups independently selected from the group consisting of an aryl group, in each of the substituents of the group represented by ring C, the aryl group in the selected group is phenyl, the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is a 5-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, the aliphatic heterocyclic moiety of the optionally substituted 5-membered monocyclic aliphatic heterocyclic group represented by ring C is a 5-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, the compound according to claim 10 or a pharmaceutically acceptable salt thereof.

12. In the group represented by the formula [II], the aliphatic heterocyclic moiety of the optionally substituted 7-membered monocyclic aliphatic heterocyclic group which may contain a double bond as part of the ring and is represented by ring B is azepanyl, oxazepanyl or diazepanyl; the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or triazolyl; the aliphatic heterocyclic moiety of the optionally substituted 5-membered monocyclic aliphatic heterocyclic group represented by ring C is azolidinyl; and in each of the substituents of the group represented by ring C, the aryl group in the selected group is phenyl. The compound according to claim 10 or 11, or a pharmaceutically acceptable salt thereof.

13. In the group represented by the formula [II], ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond as part of the ring; and ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group. The compound according to any one of claims 2 to 6, or a pharmaceutically acceptable salt thereof.

14. In the group represented by the formula [II], ring A is an optionally substituted phenyl group, the substituent of the optionally substituted phenyl group represented by ring A is a halogen atom, ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond in a part of the ring, the substituent of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring B is 1 to 3 groups independently selected from the group consisting of an oxo group, an alkyl group, and a haloalkyl group, the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring B which may contain a double bond in a part of the ring is a 6-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, ring C is an optionally substituted phenyl group or an optionally substituted 6-membered monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is a group independently selected from the group consisting of a halogen atom and a haloalkyl group, and the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. The compound according to claim 13 or a pharmaceutically acceptable salt thereof.

15. In the group represented by the formula [II], the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring B which may contain a double bond in a part of the ring is azinanyl, oxazinanyl, or diazinanyl, and the heteroaryl moiety of the optionally substituted 6-membered monocyclic heteroaryl group represented by ring C is pyridyl. The compound according to claim 13 or 14 or a pharmaceutically acceptable salt thereof.

16. In the group represented by the formula [II], ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond in a part of the ring, and ring C is an optionally substituted 5-membered monocyclic heteroaryl group. The compound according to any one of claims 2 to 6 or a pharmaceutically acceptable salt thereof.

17. In the group represented by the formula [II], ring A is an optionally substituted phenyl group; the substituent of the optionally substituted phenyl group represented by ring A is a halogen atom; ring B is an optionally substituted 6-membered monocyclic aliphatic heterocyclic group which may contain a double bond in a part of the ring; the substituent of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring B is one or two groups independently selected from the group consisting of an oxo group and an alkyl group; the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring B which may contain a double bond in a part of the ring is a 6-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; ring C is an optionally substituted 5-membered monocyclic heteroaryl group; the substituent of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is one or two groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, and a cycloalkyl group optionally substituted with one or two groups independently selected from the group consisting of a halogen atom and a haloalkyl group; the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is a 5-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur. The compound according to claim 16 or a pharmaceutically acceptable salt thereof.

18. In the group represented by the formula [II], the aliphatic heterocyclic moiety of the optionally substituted 6-membered monocyclic aliphatic heterocyclic group represented by ring B which may contain a double bond in a part of the ring is diazininyl; the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is pyrrolyl, imidazolyl, pyrazolyl or triazolyl. The compound according to claim 16 or 17 or a pharmaceutically acceptable salt thereof.

19. In the group represented by the formula [II], ring B is a 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring, and ring C is a phenyl group which may be substituted or a 6-membered monocyclic heteroaryl group which may be substituted. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 2 to 6.

20. In the group represented by the formula [II], ring A is a phenyl group which may be substituted, and the substituent of the phenyl group which may be substituted represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group and an alkoxy group; ring B is a 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring, and the substituent of the 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring represented by ring B is 1 to 3 groups independently selected from the group consisting of a hydroxyl group, an oxo group, an alkyl group and an alkylene group; the aliphatic heterocyclic part of the 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring represented by ring B is a 5-membered monocyclic aliphatic heterocyclic ring containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; ring C is a phenyl group which may be substituted or a 6-membered monocyclic heteroaryl group which may be substituted, and each of the substituents of the phenyl group which may be substituted or the 6-membered monocyclic heteroaryl group which may be substituted represented by ring C is a group independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group and an alkoxy group; the heteroaryl part of the 6-membered monocyclic heteroaryl group which may be substituted represented by ring C is a 6-membered monocyclic heteroaryl containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur. The compound or a pharmaceutically acceptable salt thereof according to claim 19.

21. In the group represented by the formula [II], the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group, which may be substituted and may contain a double bond in a part of the ring and is represented by ring B, is azolidinyl or diazolidinyl; the heteroaryl moiety of the 6-membered monocyclic heteroaryl group, which may be substituted and is represented by ring C, is pyridyl. The compound according to claim 19 or 20, or a pharmaceutically acceptable salt thereof.

22. In the group represented by the formula [II], ring B is a 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring; ring C is a 5-membered monocyclic heteroaryl group which may be substituted. The compound according to any one of claims 2 to 6, or a pharmaceutically acceptable salt thereof.

23. In the group represented by the formula [II], ring A is a phenyl group which may be substituted; the substituent of the phenyl group which may be substituted and is represented by ring A is a halogen atom; ring B is a 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring; the substituent of the 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring and is represented by ring B is one or two groups independently selected from the group consisting of an oxo group and an alkyl group; the aliphatic heterocyclic moiety of the 5-membered monocyclic aliphatic heterocyclic group which may be substituted and may contain a double bond in a part of the ring and is represented by ring B is a 5-membered monocyclic aliphatic heterocyclic ring containing one to three heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; ring C is a 5-membered monocyclic heteroaryl group which may be substituted; the substituent of the 5-membered monocyclic heteroaryl group which may be substituted and is represented by ring C is an alkyl group; the heteroaryl moiety of the 5-membered monocyclic heteroaryl group which may be substituted and is represented by ring C is a 5-membered monocyclic heteroaryl containing one to four heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur. The compound according to claim 22, or a pharmaceutically acceptable salt thereof.

24. In the group represented by the formula [II], the aliphatic heterocyclic moiety of the optionally substituted 5-membered monocyclic aliphatic heterocyclic group which may contain a double bond as part of the ring and is represented by ring B is azolidinyl, and the heteroaryl moiety of the optionally substituted 5-membered monocyclic heteroaryl group represented by ring C is thiazolyl. The compound according to claim 22 or 23, or a pharmaceutically acceptable salt thereof. (3R)-4-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one; (3R)-4-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-7-(trifluoromethyl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; (3R)-4-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethoxy)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; (3R)-4-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; (6R)-2-(1-Fluorocyclopropyl)-5-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-thiazolo[5,4-c]azepin-4-one; (7R)-2-[(1S*,5R*)-3-Azabicyclo[3.1.0]hexan-3-yl]-6-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f]oxazepin-5-one; (6R)-7-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2,6-dimethyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one; (6R)-2-(1,1-Difluoroethyl)-7-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one; (6R)-2-Cyclopropyl-7-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one;(6R)-2-(1-Fluorocyclopropyl)-7-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-5,6-dihydrothiazolo[5,4-f][1,4]oxazepin-8-one; (6R)-2-Cyclopropyl-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one; (6R)-2-(1-Fluorocyclopropyl)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one; (6R)-5-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-6-methyl-2-(trifluoromethyl)-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one; (3R)-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3,8-dimethyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one; (3R)-8-Cyclopropyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,4-f][1,4]oxazepin-5-one; (3R)-8-Cyclopropyl-4-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one; (7R)-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-2,7-dimethyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one; (7R)-2-Cyclopropyl-6-[2-(2-fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-7-methyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one;(3R)-4-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydropyrido[2,3-f][1,4]oxazepin-5-one; and a compound selected from the group consisting of (3R)-4-[2-(2-Fluorophenyl)sulfonyl-2-azaspiro[3.3]heptan-6-yl]-3-methyl-8-(trifluoromethyl)-2,3-dihydro-1H-pyrido[2,3-f][1,4]diazepin-5-one or a pharmaceutically acceptable salt thereof.

26. The compound of the formula [I] is a compound represented by the following formula [III]: [wherein ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group or an optionally substituted aliphatic heterocyclic group; ring D represents an optionally substituted aliphatic heterocyclic group which may contain a double bond as part of the ring]. The compound according to claim 1 or a pharmacologically acceptable salt thereof.

27. In the group represented by the formula [III], each substituent of the optionally substituted aryl group, optionally substituted heteroaryl group, and optionally substituted aliphatic heterocyclic group represented by ring A is independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, an alkoxyalkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkanoyl group, an alkoxycarbonyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, a sulfonyl group optionally substituted with an alkyl group, an aminocarbonyl group optionally substituted with 1 to 2 alkyl groups, a nitro group, and an aryl group, and is 1 to 3 groups; the aryl moiety of the optionally substituted aryl group represented by ring A is a 6- to 10-membered monocyclic or bicyclic aryl; the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring A is a 5- to 10-membered monocyclic or bicyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the substituent of the optionally substituted aliphatic heterocyclic group represented by ring D, which may contain a double bond in part of the ring, is 1 to 8 groups independently selected from the group consisting of an oxo group; an optionally substituted alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; an aliphatic heterocyclic group; an alkoxy group; a cycloalkoxy group; an alkylthio group; an amino group; an alkoxycarbonyl group; an alkanoyl group; an alkylsulfonyl group; a halogen atom; a hydroxyl group; and a cyano group; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring D, which may contain a double bond in part of the ring, is a 5- to 7-membered monocyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the compound according to claim 26 or a pharmaceutically acceptable salt thereof.

28. In the group represented by the formula [III], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is 1 to 2 groups independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, the substituents of the optionally substituted aliphatic heterocyclic group represented by ring D, which may contain a double bond in part of the ring, are an oxo group; an optionally substituted alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; an aliphatic heterocyclic group; an alkoxy group; a cycloalkoxy group; an alkylthio group; an amino group; an alkoxycarbonyl group; an alkanoyl group; an alkylsulfonyl group; a halogen atom; a hydroxyl group; and a cyano group, and are 1 to 8 groups independently selected from the group consisting of: in each of the substituents of the group represented by ring D, the substituents of the optionally substituted alkyl group in the selected group are a cycloalkyl group optionally substituted with an oxo group, a haloalkyl group, or a halogen atom; an aryl group optionally substituted with an alkyl group or a halogen atom; a heteroaryl group optionally substituted with an alkyl group; an aliphatic heterocyclic group optionally substituted with an oxo group; a halogen atom; a hydroxyl group; a cyano group; an alkoxy group; a cycloalkoxy group; a haloalkoxy group; an amino group; an alkylamino group; a dialkylamino group; a cycloalkylamino group; and an alkylthio group, and are 1 to 5 groups independently selected from the group consisting of: the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring D, which may contain a double bond in part of the ring, is a 5- to 7-membered monocyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur, The compound according to claim 26 or a pharmaceutically acceptable salt thereof.

29. In the group represented by the formula [III], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, and each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, and a nitro group, and is one or two groups; the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, or triazinyl; the substituents of the optionally substituted aliphatic heterocyclic group represented by ring D, which may contain a double bond in part of the ring, are an oxo group; an optionally substituted alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; an aliphatic heterocyclic group; an alkoxy group; a cycloalkoxy group; an alkylthio group; an amino group; an alkoxycarbonyl group; an alkanoyl group; an alkylsulfonyl group; a halogen atom; a hydroxyl group; and a cyano group, and are one to eight groups independently selected from the group consisting of; in each of the substituents of the group represented by ring D, the substituents of the optionally substituted alkyl group in the selected group are a cycloalkyl group optionally substituted with an oxo group, a haloalkyl group, or a halogen atom; an aryl group optionally substituted with an alkyl group or a halogen atom; a heteroaryl group optionally substituted with an alkyl group; an aliphatic heterocyclic group optionally substituted with an oxo group; a halogen atom; a hydroxyl group; a cyano group; an alkoxy group; a cycloalkoxy group; a haloalkoxy group; an amino group; an alkylamino group; a dialkylamino group; a cycloalkylamino group, and an alkylthio group, and are one to five groups independently selected from the group consisting of; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring D, which may contain a double bond in part of the ring, is azolidinyl, diazolidinyl, azinanyl, oxazinanyl, diazinanyl, thiazinanyl, azepanyl, oxazepanyl, diazepanyl, or thiazepanyl. The compound according to claim 26 or a pharmaceutically acceptable salt thereof.

30. The compound of the formula [I] is a compound represented by the following formula [IV]: [In the formula, ring A represents an optionally substituted aryl group, an optionally substituted heteroaryl group or an optionally substituted aliphatic heterocyclic group, and R １ represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted amino group, an optionally substituted alkoxy group or an optionally substituted alkylthio group, and ring E represents an optionally substituted aryl group, an optionally substituted heteroaryl group or an optionally substituted aliphatic heterocyclic group which may contain a double bond as part of the ring], the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

31. In the group represented by the formula [IV], each substituent of the optionally substituted aryl group, optionally substituted heteroaryl group, and optionally substituted aliphatic heterocyclic group represented by ring A is independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, an alkoxyalkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkanoyl group, an alkoxycarbonyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, a sulfonyl group optionally substituted with an alkyl group, an aminocarbonyl group optionally substituted with 1 to 2 alkyl groups, a nitro group, and an aryl group, and is 1 to 3 groups; the aryl moiety of the optionally substituted aryl group represented by ring A is a 6- to 10-membered monocyclic or bicyclic aryl; the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring A is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring A is a 5- to 10-membered monocyclic or bicyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; R １ is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, or an optionally substituted alkynyl group; R １ In the optionally substituted alkyl group, optionally substituted alkenyl group, and optionally substituted alkynyl group in the group represented by, the substituent is a cycloalkyl group or a cycloalkenyl group; R １ The substituents of the optionally substituted cycloalkyl group and the optionally substituted cycloalkenyl group in the group represented by are an alkyl group, an alkenyl group or an alkynyl group; the aryl moiety of the optionally substituted aryl group represented by ring E is a 6- to 10-membered monocyclic or bicyclic aryl; the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring E is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; the aliphatic heterocyclic moiety of the optionally substituted aliphatic heterocyclic group represented by ring E, which may optionally contain a double bond in a part of the ring, is a 5- to 10-membered monocyclic or bicyclic aliphatic heterocyclic containing 1 to 3 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur; the substituents of the optionally substituted aryl group, the optionally substituted heteroaryl group and the optionally substituted aliphatic heterocyclic group represented by ring E, which may optionally contain a double bond in a part of the ring, are an alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; a halogen atom; a haloalkyl group; a hydroxyl group; a cyano group; an alkoxy group; a cycloalkoxy group; an aryloxy group; a haloalkoxy group; an amino group; an alkylamino group; a dialkylamino group; a cycloalkylamino group and an alkylthio group, independently selected from the group consisting of 1 to 3 groups; the compound according to claim 30 or a pharmaceutically acceptable salt thereof.

32. In the group represented by the formula [IV], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, and each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a nitro group, and an aryl group, and is one or two groups; the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is a 5- to 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur; R １ is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkenyl group, or an optionally substituted alkynyl group, and R １ the substituents of the optionally substituted alkyl group, the optionally substituted alkenyl group, and the optionally substituted alkynyl group in the group represented by are a cycloalkyl group or a cycloalkenyl group; R １ The substituent of the optionally substituted cycloalkyl group and the optionally substituted cycloalkenyl group in the group represented by is an alkyl group, an alkenyl group or an alkynyl group, ring E is an optionally substituted aryl group or an optionally substituted heteroaryl group, the aryl moiety of the optionally substituted aryl group represented by ring E is a 6- to 10-membered monocyclic or bicyclic aryl, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring E is a 5- to 10-membered monocyclic or bicyclic heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, and the substituents of the optionally substituted aryl group and the optionally substituted heteroaryl group represented by ring E are an alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; a halogen atom; a haloalkyl group; a hydroxyl group; a cyano group; an alkoxy group; a cycloalkoxy group; an aryloxy group; a haloalkoxy group; an amino group; an alkylamino group; a dialkylamino group; a cycloalkylamino group and an alkylthio group, which are 1 to 3 groups independently selected from the group consisting of, the compound according to claim 30 or a pharmaceutically acceptable salt thereof.

33. In the group represented by the formula [IV], ring A is an optionally substituted phenyl group or an optionally substituted monocyclic heteroaryl group, and each of the substituents of the optionally substituted phenyl group or the optionally substituted monocyclic heteroaryl group represented by ring A is independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a nitro group, and an aryl group, and is one or two groups; the heteroaryl moiety of the optionally substituted monocyclic heteroaryl group represented by ring A is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, or triazinyl, R １ is an alkyl group, ring E is an optionally substituted aryl group or an optionally substituted heteroaryl group, the aryl moiety of the optionally substituted aryl group represented by ring E is phenyl or naphthyl, the heteroaryl moiety of the optionally substituted heteroaryl group represented by ring E is pyridyl, azaindolyl, imidazopyridyl, or benzimidazolyl, and in ring E, the substituents of the optionally substituted aryl group and the optionally substituted heteroaryl group are independently selected from the group consisting of an alkyl group; a cycloalkyl group; an aryl group; a heteroaryl group; a halogen atom; a haloalkyl group; a hydroxyl group; a cyano group; an alkoxy group; a cycloalkoxy group; an aryloxy group; a haloalkoxy group; an amino group; an alkylamino group; a dialkylamino group; a cycloalkylamino group, and an alkylthio group. The compound according to claim 30 or a pharmaceutically acceptable salt thereof.

34. A pharmaceutical composition comprising, as an active ingredient, the compound according to any one of claims 1 to 33 or a pharmaceutically acceptable salt thereof.

35. The pharmaceutical composition according to claim 34, which is used for the prevention or treatment of various diseases and / or symptoms associated therewith that can be improved by an increase in the central TRH concentration, or for improving the prognosis of these diseases and / or symptoms associated therewith.

36. The pharmaceutical composition according to claim 35, which is a preventive or therapeutic agent for spinocerebellar degeneration, chronic pain, sleep disorders or other mental and neurological diseases and / or symptoms associated therewith.

37. The pharmaceutical composition according to claim 36, wherein the chronic pain is neuropathic pain or nociceptive pain.

38. The pharmaceutical composition according to claim 37, wherein the neuropathic pain is pain associated with diabetic neuropathy, postherpetic neuralgia, pain associated with peripheral neuropathy due to chemotherapy, trigeminal neuralgia, complex regional pain syndrome, post-stroke pain, spinal cord injury pain, neuralgia or pain associated with nerve injury.

39. The pharmaceutical composition according to claim 37, wherein the nociceptive pain is pain associated with rheumatoid arthritis, pain associated with osteoarthritis, postoperative pain or myofascial pain.

40. The pharmaceutical composition according to claim 36, wherein the sleep disorder is hypersomnia, circadian rhythm disorder, sleep apnea or other sleep disorders.

41. The pharmaceutical composition according to claim 40, wherein the hypersomnia is narcolepsy, idiopathic hypersomnia or recurrent hypersomnia.

42. The pharmaceutical composition according to claim 40, wherein the circadian rhythm disorder is sleep disorder due to shift work, delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome or irregular sleep-wake pattern.

43. The pharmaceutical composition according to claim 40, wherein the sleep apnea is sleep apnea syndrome.

44. The pharmaceutical composition according to claim 40, wherein the other sleep disorders are jet lag syndrome, desynchronosis syndrome, restless legs syndrome, periodic limb movement disorder, hypersomnia associated with insomnia complicated by neurological or mental diseases or REM sleep behavior disorder.

45. The pharmaceutical composition according to claim 36, wherein the other mental and neurological diseases and / or symptoms associated therewith are spinal muscular atrophy, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, chronic fatigue syndrome, vascular dementia, bipolar disorder, depression, spinal cord injury, cerebral infarction, head trauma, locked-in syndrome, language disorder, easy fatigability, functional disorder caused by nerve injury or functional disorder caused by surgical operation.

46. A method for treating various diseases and / or symptoms associated therewith that can be improved by an increase in central TRH concentration, comprising administering to a patient a therapeutically effective amount of the compound according to any one of claims 1 to 33 or a pharmaceutically acceptable salt thereof.

47. The treatment method according to claim 46, wherein the various diseases and / or symptoms associated therewith that can be improved by an increase in central TRH concentration are spinocerebellar degeneration, pain, sleep disorder or other mental and neurodegenerative diseases and / or symptoms associated therewith.