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WO2014024993A1 - Piperazine derivative and use thereof - Google Patents

Piperazine derivative and use thereof Download PDF

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Publication number
WO2014024993A1
WO2014024993A1 PCT/JP2013/071557 JP2013071557W WO2014024993A1 WO 2014024993 A1 WO2014024993 A1 WO 2014024993A1 JP 2013071557 W JP2013071557 W JP 2013071557W WO 2014024993 A1 WO2014024993 A1 WO 2014024993A1
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Prior art keywords
group
optionally substituted
compound
ring
salt
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PCT/JP2013/071557
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French (fr)
Japanese (ja)
Inventor
高須　清誠
恭史 奥野
恵里 瀬木
貴史 原
駿 藤村
佳宏 山本
千里 金井
達也 吉川
正博 閨
晋哉 河野
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KYOTO CONSTELLA TECHNOLOGIES Co Ltd
KNC Laboratories Co Ltd
Kyoto University NUC
Original Assignee
KYOTO CONSTELLA TECHNOLOGIES Co Ltd
KNC Laboratories Co Ltd
Kyoto University NUC
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Publication of WO2014024993A1 publication Critical patent/WO2014024993A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Definitions

  • the present invention has an arginine-vasopressin 1b (hereinafter also referred to as V1b) receptor antagonistic action, and has a central psychiatric disorder (mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder) And a compound useful as a prophylactic or therapeutic agent in diseases such as epilepsy.
  • V1b arginine-vasopressin 1b
  • V1b receptors are involved in ACTH secretion from the posterior lobe of the pituitary gland, and are thought to be responsible for various psychoregulatory functions throughout the brain.
  • the V1b receptor has been suggested to be associated with mood disorders and anxiety disorders, and the usefulness of V1b receptor antagonists has been studied.
  • Arginine-vasopressin is a 9-amino acid peptide that is biosynthesized mainly in the hypothalamus and is involved in the regulation of plasma osmotic pressure, blood pressure, and body fluid volume as a pituitary posterior lobe hormone. In addition, its presence has been confirmed in a wide area in the brain, suggesting that it is involved in the mechanism of mental function regulation.
  • the AVP receptor has three subtypes of V1a, V1b and V2 receptors, all of which are 7-transmembrane receptors.
  • the V1b receptor like the V1a receptor, is coupled to Gq / 11 and promotes the PI response.
  • V1b receptors are most abundant in the pituitary gland and are involved in ATH secretion from the posterior pituitary gland by AVP. In addition to the pituitary gland, it is distributed over a wide area of the brain, and is also present in the limbic system such as the hippocampus, amygdala, and olfactory cortex, the cerebral cortex, the olfactory bulb, and the raphe nucleus, which is the origin of the serotonin nervous system. In recent years, it has been suggested that the V1b receptor is associated with mood disorders and anxiety disorders, and the usefulness of V1b receptor antagonists has been studied. In addition, it has been reported that an anxiolytic-like action of a V1b receptor antagonist and an antidepressant and anxiolytic action in various animal models.
  • Patent Documents 1 to 11 and Non-Patent Documents 1 to 5 are known as compounds having a V1b receptor antagonistic activity, but the structure is completely different from that of the present compound.
  • An object of the present invention is to provide a compound having a V1b receptor antagonistic action.
  • Ring A represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 1 is (1) —CH ⁇ CH—R x (wherein R x represents an optionally substituted C 6-14 aryl group or an optionally substituted aromatic heterocyclic group).
  • R y represents an optionally substituted C 6-14 aryl group.
  • R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom or a substituent;
  • R 6 is optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show.
  • An arginine-vasopressin 1b receptor antagonist comprising a compound represented by formula (hereinafter also referred to as compound (I)) or a salt thereof.
  • Ring A represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom or a substituent;
  • R 6 is optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show.
  • An arginine-vasopressin 1b receptor antagonist comprising a compound represented by the formula:
  • Ring Aa represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 1a represents an optionally substituted C 6-14 aryl group, or an optionally substituted aromatic heterocyclic group
  • At least one of R 2a , R 3a , R 4a and R 5a represents a substituent, and the rest each independently represents a hydrogen atom or a substituent
  • R 6a represents an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group.
  • a salt thereof hereinafter also referred to as compound (Ia)
  • [2a] General formula (Ia):
  • Ring Aa represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 1a represents an optionally substituted C 6-14 aryl group
  • At least one of R 2a , R 3a , R 4a and R 5a represents a substituent, and the rest each independently represents a hydrogen atom or a substituent
  • R 6a represents an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group.
  • Ring Ab represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 1b is (1) a C 6-14 aryl group substituted with a nitro group and a C 1-6 alkoxy group, (2) optionally substituted benzofuryl, or (3) represents an optionally substituted indanyl
  • R 2b , R 3b , R 4b and R 5b each independently represent a hydrogen atom or a substituent
  • R 6b represents an optionally substituted C 6-14 aryl group.
  • a salt thereof hereinafter also referred to as compound (Ib)
  • Ring Ab represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 1b represents a C 6-14 aryl group substituted with a nitro group and a C 1-6 alkoxy group
  • R 2b , R 3b , R 4b and R 5b each independently represent a hydrogen atom or a substituent
  • R 6b represents an optionally substituted C 6-14 aryl group.
  • R 1b is (1) a C 6-10 aryl group substituted with one nitro group and one or two C 1-6 alkoxy groups, (2) benzofuryl, or (3) The compound or a salt thereof according to the above [7], which is indanyl.
  • Ring Ac represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 1c represents an optionally substituted C 6-14 aryl group
  • R 2c , R 3c , R 4c and R 5c each independently represent a hydrogen atom or a substituent
  • R 6c is an optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show.
  • a salt thereof hereinafter also referred to as compound (Ic)
  • R 6c is, C 1-6 alkyl group optionally substituted C 6-10 aryl group, C 1-6 alkyl optionally substituted C 7-16 aralkyl group, or a group C 6,
  • Ring Ad represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring
  • R 1d represents an optionally substituted C 6-14 aryl group
  • At least one of R 2d , R 3d , R 4d and R 5d represents a substituent, and the rest each independently represents a hydrogen atom or a substituent
  • R 6d represents an optionally substituted C 6-14 aryl group
  • n d represents an integer of 1 to 5.
  • a salt thereof hereinafter also referred to as compound (Id)).
  • a pharmaceutical composition comprising the compound according to any one of [2] to [21] above or a salt thereof, and a pharmaceutically acceptable carrier.
  • Mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder or epilepsy containing the compound or salt thereof according to any one of [1] to [21] above Preventive or therapeutic agent.
  • Compound (I) has a V1b receptor antagonism, and thus has a central psychiatric disorder (mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, epilepsy, etc.) It is useful as a preventive or therapeutic agent.
  • a central psychiatric disorder mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, epilepsy, etc.
  • halogen atom in the present specification include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • substituted includes “optionally substituted hydrocarbon group”, “optionally substituted heterocyclic group”, “optionally substituted hydroxy group”, “substituted” And optionally substituted amino group, “optionally substituted sulfanyl group”, “acyl group”, “halogen atom”, “cyano group”, “nitro group” and the like.
  • Examples of the “optionally substituted hydrocarbon group” in the present specification include “an optionally substituted C 1-10 alkyl group” and “an optionally substituted C 2-10 alkenyl group”.
  • An optionally substituted C 6-10 aryl-C 2-6 alkenyl group ”.
  • C 1-10 alkyl group examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl and hexyl. , Isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, octyl, nonyl, decyl and the like. Of these, a C 1-6 alkyl group is preferable.
  • C 1-6 alkyl (group) examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl. Hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl and the like.
  • C 2-10 alkenyl group examples include ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3- Methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, 5-hexenyl, 1-heptenyl, 1-octenyl, etc. Is mentioned. Of these, a C 2-6 alkenyl group is preferable.
  • C 2-6 alkenyl (group) examples include ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, Examples include 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, 5-hexenyl and the like.
  • C 2-10 alkynyl group examples include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3- Examples include pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-heptynyl, 1-octynyl and the like. Of these, a C 2-6 alkynyl group is preferable.
  • C 2-6 alkynyl (group) examples include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, Examples include 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl and the like.
  • Examples of the “C 3-10 cycloalkyl group” in the present specification include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and the like. Of these, a C 3-6 cycloalkyl group is preferable.
  • Examples of the “C 3-8 cycloalkyl (group)” in the present specification include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. Of these, a C 3-6 cycloalkyl group is preferable.
  • C 3-10 cycloalkenyl group examples include 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl and 3-cyclohexen-1-yl. Etc. Of these, a C 3-6 cycloalkenyl group is preferable.
  • C 3-8 cycloalkenyl (group) includes, for example, 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexene-1 -Yl and the like. Of these, a C 3-6 cycloalkenyl group is preferable.
  • C 4-10 cycloalkadienyl group examples include 2,4-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadiene- 1-yl and the like can be mentioned. Of these, a C 4-6 cycloalkadienyl group is preferable.
  • C 4-8 cycloalkadienyl (group)” includes, for example, 2,4-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl, 2,5-cyclo And hexadien-1-yl. Of these, a C 4-6 cycloalkadienyl group is preferable.
  • C 3-10 cycloalkyl group “C 3-10 cycloalkenyl group” and “C 4-10 cycloalkadienyl group” are each condensed with a benzene ring to form a condensed ring group.
  • Examples of such a condensed ring group include indanyl, dihydronaphthyl, tetrahydronaphthyl, fluorenyl and the like.
  • C 6-14 aryl (group) examples include phenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl, biphenylyl and the like.
  • the “C 6-14 aryl (group)” may be condensed with another ring, and examples thereof include fluorenyl, dihydronaphthyl, tetrahydronaphthyl and the like. Of these, a C 6-10 aryl group is preferable.
  • C 7-16 aralkyl (group) examples include benzyl, phenethyl, naphthylmethyl, biphenylylmethyl and the like. Of these, a C 7-13 aralkyl group is preferable.
  • Examples of the “C 6-10 aryl-C 2-6 alkenyl group” in the present specification include styryl, 3-phenyl-2-propenyl and the like. Of these, a C 6-10 aryl-C 2-4 alkenyl group is preferable.
  • C 1-6 alkoxy (group) examples include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy and the like.
  • heterocycle (group) examples include an aromatic heterocyclic group and a non-aromatic heterocyclic group.
  • aromatic heterocyclic group in the present specification include 4 to 7-membered (containing 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom in addition to a carbon atom as a ring-constituting atom ( And preferably monocyclic aromatic heterocyclic groups and condensed aromatic heterocyclic groups (preferably those having 8 to 12 members).
  • Examples of the condensed aromatic heterocyclic group include a ring corresponding to the 4- to 7-membered monocyclic aromatic heterocyclic group and a 5- or 6-membered aromatic heterocyclic ring containing 1 or 2 nitrogen atoms.
  • a ring corresponding to the 4- to 7-membered monocyclic aromatic heterocyclic group and a 5- or 6-membered aromatic heterocyclic ring containing 1 or 2 nitrogen atoms.
  • Examples include groups to be derived.
  • Monocyclic aromatic heterocyclic groups such as furyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl; Quinolyl, isoquinolyl, quinazolyl, quinoxalyl, benzofuryl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzimidazolyl, benzotriazolyl, indolyl, indazolyl, carbazolyl, pyrrolopyrazinyl, imidazopyridyl, thienopyr
  • non-aromatic heterocyclic group examples include 4 to 7 members containing 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom in addition to a carbon atom as a ring constituent atom. (Preferably 5 or 6 membered) monocyclic non-aromatic heterocyclic group and condensed non-aromatic heterocyclic group (preferably having 8 to 12 members).
  • monocyclic non-aromatic heterocyclic group and condensed non-aromatic heterocyclic group (preferably having 8 to 12 members).
  • condensed non-aromatic heterocyclic group examples include a ring corresponding to the 4- to 7-membered monocyclic non-aromatic heterocyclic group, and a 5- or 6-membered aromatic containing 1 or 2 nitrogen atoms.
  • 1 or 2 rings selected from a heterocycle (eg, pyrrole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine), a 5-membered aromatic heterocycle containing one sulfur atom (eg, thiophene) and a benzene ring
  • a heterocycle eg, pyrrole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine
  • a 5-membered aromatic heterocycle containing one sulfur atom eg, thiophene
  • benzene ring examples thereof include a group derived from a condensed ring and a group obtained by partial saturation of the group.
  • non-aromatic heterocyclic group Azetidinyl, pyrrolidinyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, hexamethyleneiminyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, oxazolinyl, thiazolinyl, imidazolinyl, dioxolyl, dioxolanyl, dihydrooxadiazolyl, thiol, pyranyl Monocyclic non-aromatic heterocyclic groups such as tetrahydrofuryl, pyrazolidinyl, pyrazolinyl, tetrahydropyrimidinyl, dihydrotriazolyl, tetrahydrotriazolyl; Dihydroindolyl, dihydroisoindolyl, dihydrobenzofuranyl, dihydro
  • fused ring group for example, a condensed aromatic heterocyclic group (preferably 8 to 12-membered), a condensed non-aromatic heterocyclic group (preferably 8 to 12-membered), Examples thereof include a condensed C 10-14 aryl group and a condensed non-aromatic hydrocarbon group (preferably having 8 to 12 members).
  • the “fused aromatic heterocyclic group” and “fused non-aromatic heterocyclic group” include the above-mentioned “fused aromatic heterocyclic group” and “fused non-aromatic heterocyclic group”.
  • Examples of the “fused C 10-14 aryl group” include a group derived from a condensed ring having 10 to 14 carbon atoms in the above “C 6-14 aryl group”.
  • Examples of the “condensed non-aromatic hydrocarbon group” include the above-mentioned “C 3-10 cycloalkyl group”, “C 3-10 cycloalkenyl group” and “C 4-10 cycloalkadienyl group”. Examples thereof include those condensed with a benzene ring.
  • the “5- to 7-membered nitrogen-containing saturated heterocyclic ring” in the present specification includes, for example, at least one nitrogen atom in addition to a carbon atom as a ring constituent atom, and is further selected from an oxygen atom, a sulfur atom and a nitrogen atom. Examples thereof include a 5- to 7-membered nitrogen-containing saturated heterocyclic ring which may contain 1 to 2 heteroatoms.
  • nitrogen-containing saturated heterocyclic ring examples include pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, thiazolidine, piperidine, piperazine, azepane, morpholine, thiomorpholine, and among them, pyrrolidine, piperidine and azepane are preferable.
  • the number of substituents is not particularly limited as long as it can be substituted, but is preferably 1 to 5, more preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different. The substituent may be further substituted with the substituent A.
  • Examples of the “optionally substituted hydroxy group” in the present specification include “an optionally substituted C 1-10 alkyl group”, “an optionally substituted C 2-10 alkenyl group”, “Optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “ optionally substituted C 6-14 aryl group”, “substituted Substituents selected from “ optionally substituted C 7-16 aralkyl group”, “ optionally substituted C 6-10 aryl-C 2-6 alkenyl group”, “optionally substituted heterocyclic group”, etc. And a hydroxy group which may be substituted with.
  • Examples of the “optionally substituted sulfanyl group” in the present specification include “an optionally substituted C 1-10 alkyl group”, “an optionally substituted C 2-10 alkenyl group”, “Optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “ optionally substituted C 6-14 aryl group”, “substituted Substituents selected from “ optionally substituted C 7-16 aralkyl group”, “ optionally substituted C 6-10 aryl-C 2-6 alkenyl group”, “optionally substituted heterocyclic group”, etc. And a sulfanyl group which may be substituted with.
  • Examples of the “optionally substituted amino group” in the present specification include “an optionally substituted C 1-10 alkyl group”, “an optionally substituted C 2-10 alkenyl group”, “Optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “ optionally substituted C 6-14 aryl group”, “substituted Optionally substituted C 7-16 aralkyl group ”,“ optionally substituted C 6-10 aryl-C 2-6 alkenyl group ”,“ optionally substituted heterocyclic group ”,“ acyl group ”, etc. And an amino group which may be mono- or di-substituted with a substituent selected from:
  • acyl group in the present specification, for example, the formula: -COR A, -CO-OR A , -S (O) 2 R A, -SOR A, -CO-NR A 'R B', - CS-NR A 'R B ', -S (O) 2 NR A 'R B ' [wherein, R A represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted complex. A ring group is shown.
  • R A ′ and R B ′ are the same or different and each represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group, or R A ′ and R B ′ are A nitrogen-containing heterocyclic ring which may be substituted with an adjacent nitrogen atom may be formed], and the like.
  • the “nitrogen-containing heterocycle” in the “optionally substituted nitrogen-containing heterocycle” formed by R A ′ and R B ′ together with the adjacent nitrogen atom includes, for example, at least one ring-constituting atom other than a carbon atom And a 5- to 7-membered nitrogen-containing heterocyclic ring which may contain 1 to 2 heteroatoms selected from oxygen, sulfur and nitrogen atoms.
  • the nitrogen-containing heterocycle include pyrrolidine, imidazolidine, pyrazolidine, piperidine, piperazine, azepane, morpholine, thiomorpholine and the like.
  • the nitrogen-containing heterocycle may have 1 to 5 (preferably 1 or 2) substituents at substitutable positions.
  • substituents include the above-described substituent A.
  • each substituent may be the same or different.
  • Ring A represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring which may be substituted.
  • the “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring A is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
  • Ring A is Preferably, each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted, More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl), More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is a piperidine ring.
  • R 1 is (1) —CH ⁇ CH—R x (wherein R x represents an optionally substituted C 6-14 aryl group or an optionally substituted aromatic heterocyclic group).
  • R 1 is preferably (1) —CH ⁇ CH—R x (wherein R x is an optionally substituted C 6-10 aryl group (preferably phenyl), or an optionally substituted 5- or 6-membered monocycle) A group represented by the formula aromatic heterocyclic group (preferably pyridyl); (2) a group represented by —CH 2 —O—R y (wherein R y is an optionally substituted C 6-10 aryl group (preferably phenyl)); (3) — (CH 2 ) n —R z (wherein R z is an optionally substituted C 6-10 aryl group (preferably phenyl), and n is an integer of 1 to 5) A group represented by: (4) an optionally substituted C 6-10 aryl group (preferably phenyl, naphthyl); (5) an optionally substituted 8- to 12-membered fused aromatic heterocyclic group (preferably benzofuryl); or (6) An optionally substituted 8- to 12-membered condensed non-ar
  • R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom or a substituent.
  • R 2 , R 3 , R 4 and R 5 are each independently a hydrogen atom or an optionally substituted C 1-6 alkyl group (preferably methyl).
  • at least one of R 2 , R 3 , R 4 and R 5 is a substituent, and the rest are each independently a hydrogen atom or a substituent.
  • at least one of R 2 , R 3 , R 4 and R 5 is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom.
  • it is an optionally substituted C 1-6 alkyl group (preferably methyl).
  • R 2 , R 3 , R 4 and R 5 is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl). Even more preferably, one of R 2 , R 3 , R 4 and R 5 is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms. Particularly preferably, among R 2 , R 3 , R 4 and R 5 , R 3 or R 4 is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
  • R 6 is optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show.
  • R 6 is Preferably, a C 6-14 aryl group (preferably phenyl), a C 7-16 aralkyl group (preferably benzyl) or C 6-, each optionally substituted with a C 1-6 alkyl group (preferably methyl).
  • C 1-6 alkyl group (preferably methyl) optionally C 6-10 aryl group optionally substituted by (preferably phenyl), C 1-6 alkyl group (preferably methyl) substituted with Or a C 7-16 aralkyl group (preferably benzyl) or a C 6-10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl); More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).
  • Ring Aa represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring.
  • the “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring Aa is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
  • Ring Aa is Preferably, each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted, More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl), More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is a piperidine ring.
  • R 1a represents an optionally substituted C 6-14 aryl group or an optionally substituted aromatic heterocyclic group.
  • R 1a is Preferably, it is an optionally substituted C 6-10 aryl group (preferably phenyl), or an optionally substituted 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl).
  • a C 6-10 aryl group preferably phenyl or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl), each of which may be substituted with a nitro group
  • it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group, or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl)
  • Particularly preferred is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group.
  • At least one of R 2a , R 3a , R 4a and R 5a represents a substituent, and the rest each independently represents a hydrogen atom or a substituent.
  • at least one of R 2a , R 3a , R 4a and R 5a is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or An optionally substituted C 1-6 alkyl group (preferably methyl).
  • at least one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
  • R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
  • R 2a , R 3a , R 4a and R 5a , R 3a or R 4a is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
  • R 6a represents an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group.
  • R 6a is Preferably, it is a C 6-14 aryl group (preferably phenyl) or a C 7-16 aralkyl group (preferably benzyl), each optionally substituted with a C 1-6 alkyl group (preferably methyl). More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl), or a C 7-13 aralkyl group (preferably benzyl).
  • it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).
  • the bond of R 1a may be any of (E) and (Z) with respect to carbonyl, but is preferably (E).
  • Ring Ab represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring which may be substituted.
  • the “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring Ab is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
  • Ring Ab is Preferably, each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted, More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl), More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is a piperidine ring.
  • R 1b is (1) a C 6-14 aryl group substituted with a nitro group and a C 1-6 alkoxy group, (2) optionally substituted benzofuryl, or (3) Indanyl which may be substituted.
  • R 1b is Preferably, (1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy), (2) optionally substituted benzofuryl, or (3) optionally substituted indanyl, More preferably, (1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy), (2) benzofuryl, or (3) Indanyl, More preferably, (1) a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two (preferably one) C 1-6 alkoxy groups (preferably methoxy, ethoxy), (2)
  • R 2b , R 3b , R 4b and R 5b each independently represent a hydrogen atom or a substituent.
  • R 2b , R 3b , R 4b and R 5b are each independently a hydrogen atom or an optionally substituted C 1-6 alkyl group (preferably methyl).
  • at least one of R 2b , R 3b , R 4b and R 5b is a substituent, and the rest are each independently a hydrogen atom or a substituent.
  • at least one of R 2b , R 3b , R 4b and R 5b is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom.
  • R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
  • one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms.
  • R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
  • R 6b represents an optionally substituted C 6-14 aryl group.
  • R 6b is Preferably, it is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl). More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl). More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).
  • Ring Ac represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring.
  • Ring Ac is preferably a pyrrolidine ring, piperidine ring or azepane ring, more preferably a piperidine ring.
  • R 1c represents an optionally substituted C 6-14 aryl group.
  • R 1c is Preferably, it is an optionally substituted C 6-10 aryl group (preferably phenyl), More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group.
  • R 2c , R 3c , R 4c and R 5c each independently represent a hydrogen atom or a substituent.
  • R 2c , R 3c , R 4c and R 5c are each independently a hydrogen atom or an optionally substituted C 1-6 alkyl group (preferably methyl).
  • at least one of R 2c , R 3c , R 4c and R 5c is a substituent, and the rest are each independently a hydrogen atom or a substituent.
  • R 2c , R 3c , R 4c and R 5c is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom Alternatively, it is an optionally substituted C 1-6 alkyl group (preferably methyl). More preferably, at least one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl). Even more preferably, one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms. Particularly preferably, among R 2c , R 3c , R 4c and R 5c , R 3c or R 4c is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
  • R 6c is an optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show.
  • R 6c is Preferably, a C 6-14 aryl group (preferably phenyl), a C 7-16 aralkyl group (preferably benzyl) or C 6-, each optionally substituted with a C 1-6 alkyl group (preferably methyl).
  • C 1-6 alkyl group (preferably methyl) optionally C 6-10 aryl group optionally substituted by (preferably phenyl), C 1-6 alkyl group (preferably methyl) substituted with Or a C 7-16 aralkyl group (preferably benzyl) or a C 6-10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl); More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).
  • Ring Ad represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring.
  • the “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring Ad is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
  • each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted, More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl), More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is a piperidine ring.
  • R 1d represents an optionally substituted C 6-14 aryl group.
  • R 1d is Preferably, it is an optionally substituted C 6-10 aryl group (preferably phenyl), More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group, Particularly preferred is a C 6-10 aryl group (preferably phenyl).
  • At least one of R 2d , R 3d , R 4d and R 5d represents a substituent, and the rest each independently represents a hydrogen atom or a substituent.
  • at least one of R 2d , R 3d , R 4d and R 5d is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or An optionally substituted C 1-6 alkyl group (preferably methyl).
  • at least one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
  • one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
  • R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
  • R 6d represents an optionally substituted C 6-14 aryl group.
  • R 6d is Preferably, it is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl). More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl). More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl), Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).
  • n d represents an integer of 1 to 5.
  • n d is preferably an integer of 1 to 3, and more preferably 3.
  • compound (I), compound (Ia), compound (Ib), compound (Ic) and compound (Id) are novel compounds.
  • preferred compounds, compound (Ia), compound (Ib), compound (Ic) and compound (Id) are shown.
  • Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
  • R 1a is an optionally substituted C 6-10 aryl group (preferably phenyl);
  • At least one of R 2a , R 3a , R 4a and R 5a is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted
  • R 6a is an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group.
  • Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
  • R 1a is an optionally substituted C 6-10 aryl group (preferably phenyl), or an optionally substituted 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl);
  • At least one of R 2a , R 3a , R 4a and R 5a is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted
  • R 6a is an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group.
  • Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • At least one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And a C 6-14 aryl group (preferably phenyl) or a C 7-16 aralkyl group (preferably R 6a ), each optionally substituted with a C 1-6 alkyl group (preferably methyl).
  • Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1a is a C 6-10 aryl group (preferably phenyl) or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl), each optionally substituted with a nitro group;
  • At least one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And a C 6-14 aryl group (preferably phenyl) or a C 7-16 aralkyl group (preferably R 6a ), each optionally substituted with a C 1-6 alkyl group (preferably methyl).
  • Ring Aa is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • One of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and
  • R 6a is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), or a C 7-13 aralkyl group (preferably benzyl).
  • Compound (Ia) is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • Ring Aa is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group, or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl);
  • One of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and
  • R 6a is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), or a C 7-13 aralkyl group (preferably benzyl).
  • Compound (Ia) is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1a is a C 6-10 aryl group (preferably phenyl
  • Ring Aa is a piperidine ring;
  • R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • R 2a , R 3a , R 4a and R 5a , R 3a or R 4a is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms; and
  • R 6a is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl), Compound (Ia).
  • Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
  • R 1b is a C 6-14 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
  • At least one of R 2b , R 3b , R 4b and R 5b is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted
  • R 6b is an optionally substituted C 6-14 aryl group, Compound (Ib).
  • Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
  • R 1b is (1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy), (2) optionally substituted benzofuryl, or (3) optionally substituted indanyl;
  • At least one of R 2b , R 3b , R 4b and R 5b is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted
  • R 6b is an optionally substituted C 6-14 aryl group, Compound (Ib).
  • Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1b is a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
  • At least one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably
  • R 6b is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
  • Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1b is (1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy), (2) optionally substituted benzofuryl, or (3) optionally substituted indanyl;
  • At least one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably
  • R 6b is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
  • Ring Ab is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1b is a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
  • One of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and
  • R 6b is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), Compound (Ib).
  • Ring Ab is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1b is (1) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy) (preferably one nitro group and one or two (preferably one) C 1-6 alkoxy groups)
  • a C 6-10 aryl group preferably phenyl
  • R 4b and R 5b is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and
  • R 6b is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), Compound (Ib).
  • Ring Ab is a piperidine ring
  • R 1b is a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two (preferably one) C 1-6 alkoxy groups (preferably methoxy, ethoxy). Yes; Of R 2b , R 3b , R 4b and R 5b , R 3b or R 4b is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms; and R 6b is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl), Compound (Ib).
  • Ring Ab is a piperidine ring
  • R 1b is (1) a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two (preferably one) C 1-6 alkoxy groups (preferably methoxy, ethoxy), or (2) indanyl
  • R 2b , R 3b , R 4b and R 5b , R 3b or R 4b is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms
  • R 6b is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl), Compound (Ib).
  • Ring Ac is a pyrrolidine ring, piperidine ring or azepane ring;
  • R 1c is an optionally substituted C 6-10 aryl group (preferably phenyl);
  • At least one of R 2c , R 3c , R 4c and R 5c is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted be a C 1-6 alkyl group be a (preferably methyl);
  • R 6c is an optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group or a substituted, An optionally substituted C 6-10 aryl-C 2-6 alkenyl group, Compound (Ic).
  • Ring Ac is a pyrrolidine ring, piperidine ring or azepane ring;
  • R 1c is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • At least one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And a C 6-14 aryl group (preferably phenyl), a C 7-16 aralkyl group (preferably phenyl), and R 6c each optionally substituted with a C 1-6 alkyl group (preferably methyl).
  • Ring Ac is a piperidine ring;
  • R 1c is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • One of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and
  • R 6c is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), a C 7-16 aralkyl group (preferably benzyl) optionally substituted with a C 1-6 alkyl group (preferably methyl) Or a C 6-10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl), Compound (Ic).
  • Ring Ac is a piperidine ring;
  • R 1c is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • R 2c , R 3c , R 4c and R 5c , R 3c or R 4c is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms; and
  • R 6c is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl), Compound (Ic).
  • Ring Ad is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
  • R 1d is an optionally substituted C 6-10 aryl group (preferably phenyl);
  • At least one of R 2d , R 3d , R 4d and R 5d is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted
  • R 6d is an optionally substituted C 6-14 aryl group; and
  • nd is an integer of 1 to 5, Compound (Id).
  • Ring Ad is a pyrrolidine ring, piperidine ring or azepane ring, each optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1d is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
  • At least one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably Methyl);
  • R 6d is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl); and
  • nd is an integer of 1 to 5, Compound (Id).
  • Ring Ad is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
  • R 1d is a C 6-10 aryl group (preferably phenyl);
  • One of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms;
  • R 6d is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl); and
  • n d is an integer of 1 to 3 (preferably 3 ) Compound (Id).
  • Ring Ad is a piperidine ring;
  • R 1d is a C 6-10 aryl group (preferably phenyl);
  • R 2d , R 3d , R 4d and R 5d R 3d or R 4d is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms;
  • R 6d is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl); and
  • nd is an integer of 1 to 3 (preferably 3) , Compound (Id).
  • compound (I) When compound (Ia), compound (Ib), compound (Ic), compound (Id) or compound (I) (hereinafter collectively referred to as compound (I)) is a salt, examples thereof include metal salts, ammonium salts, salts with organic bases, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids, and the like.
  • metal salt include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt, magnesium salt and barium salt; aluminum salt and the like.
  • the salt with organic base include, for example, trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N, N′-dibenzyl.
  • Examples include salts with ethylenediamine and the like.
  • Preferable examples of the salt with inorganic acid include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
  • salt with organic acid examples include, for example, formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzene Examples thereof include salts with sulfonic acid, p-toluenesulfonic acid and the like.
  • salts with basic amino acids include salts with arginine, lysine, ornithine and the like, and preferable examples of salts with acidic amino acids include salts with aspartic acid, glutamic acid and the like. Is mentioned. Of these, pharmaceutically acceptable salts are preferred.
  • inorganic salts such as alkali metal salts (eg, sodium salts, potassium salts, etc.), alkaline earth metal salts (eg, calcium salts, magnesium salts, etc.), ammonium salts
  • a salt with an inorganic acid such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, or acetic acid, phthalic acid, fumaric acid
  • organic acids such as acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.
  • Each raw material compound may form a salt as long as it does not inhibit the reaction.
  • Examples of such a salt include the same salts as the salt of compound (I).
  • a raw material compound can be easily obtained and used commercially, or can be produced according to a method known per se or a method analogous thereto.
  • Compound (I) can be produced according to Reaction Schemes 1-2.
  • P 1 represents a protecting group for a carboxy group, and other symbols are as defined above.
  • Examples of the “carboxy-protecting group” represented by P 1 include a C 1-6 alkyl group (methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.), phenyl group, trityl group, silyl group
  • These protecting groups may have a substituent.
  • substituents examples include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), formyl groups, C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups, etc.
  • the number of substituents is about 1 to 3.
  • a C 1-6 alkyl group is preferred, and methyl and ethyl are particularly preferred.
  • This step is a step of obtaining compound (3) by reacting compound (1) with compound (2) in a solvent in the presence of a condensing agent.
  • the amount of compound (2) to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (1).
  • the condensing agent include dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC ⁇ HCl), and the like.
  • the amount of the condensing agent to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (1). If necessary, the reaction may be carried out in the presence of a condensation accelerator or the like or a base.
  • condensation accelerator examples include 1-hydroxybenzotriazole (HOBt) monohydrate.
  • the amount of the condensation accelerator used is usually 1 to 2 equivalents, preferably 1 to 1.2 equivalents, relative to compound (1).
  • the base examples include organic bases such as triethylamine, N, N-diisopropylethylamine, 4- (dimethylamino) pyridine (DMAP), and pyridine.
  • the amount of the base to be used is generally 0.1-2 equivalents, preferably 0.1-1.2 equivalents, relative to compound (1).
  • the solvent include methylene chloride, N, N-dimethylformamide, chloroform and the like.
  • the reaction temperature is usually 0 to 35 ° C., preferably 15 to 25 ° C., and the reaction time is usually 1 to 24 hours.
  • compound (3) can be produced by converting compound (1) to an acid halide using a halogenating agent and then reacting with compound (2) in a solvent in the presence of a base.
  • the amount of compound (2) to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (1).
  • the halogenating agent include thionyl chloride, oxalyl chloride, phosphorus trichloride, sulfuryl chloride and the like.
  • the amount of the halogenating agent to be used is generally 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to compound (1).
  • the base include organic bases such as triethylamine, N, N-diisopropylethylamine, and pyridine.
  • the amount of the base to be used is generally 1 to 2 equivalents, preferably 1 to 1.2 equivalents, relative to compound (1).
  • the solvent include methylene chloride, chloroform, toluene, tetrahydrofuran and the like.
  • the reaction temperature is usually 0 to 45 ° C., preferably 0 to 25 ° C., and the reaction time is usually 1 to 24 hours.
  • This step is a step of obtaining compound (4) by deprotecting compound (3).
  • Deprotection is performed, for example, by reacting compound (3) with a base in a solvent.
  • the base include sodium hydroxide, potassium hydroxide, lithium hydroxide and the like.
  • the amount of the base to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (3).
  • the solvent include methanol, ethanol, tetrahydrofuran, 1,4-dioxane and the like. These are preferably used by mixing with water at an appropriate ratio.
  • the reaction temperature is usually 0 to 80 ° C., preferably 15 to 25 ° C., and the reaction time is usually 1 to 24 hours.
  • Process 3 This step is a step in which compound (I) is obtained by reacting compound (4) with compound (5). This step is performed by the same method as in step 1 of the manufacturing route (1).
  • P 2 represents an amino-protecting group, and other symbols are as defined above.
  • amino-protecting group represented by P 2 include a formyl group, a C 1-6 alkyl-carbonyl group (acetyl, propionyl, etc.), a phenylcarbonyl group, a C 1-6 alkyl-oxycarbonyl group (methoxycarbonyl, Ethoxycarbonyl, tert-butoxycarbonyl etc.), aryloxycarbonyl group (phenyloxycarbonyl etc.), C 7-10 aralkyl-carbonyl group (benzyloxycarbonyl etc.), benzyl group, benzhydryl group, trityl group, phthaloyl group etc.
  • These protecting groups may have a substituent.
  • substituents include halogen atoms (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups and the like.
  • the number of substituents is about 1 to 3. Preferred are tert-butoxycarbonyl and benzyloxycarbonyl.
  • This step is a step of obtaining the compound (7) by reacting the compound (6) with the compound (5). This step is performed by the same method as in step 1 of the manufacturing route (1).
  • This step is a step of obtaining compound (8) by deprotecting compound (7).
  • Deprotection is performed, for example, by reacting compound (7) with an acid in a solvent when P 2 is tert-butoxycarbonyl or the like.
  • the acid include hydrochloric acid, trifluoroacetic acid (TFA), formic acid and the like.
  • the amount of the acid to be used is generally 2-100 equivalents, preferably 5-10 equivalents, relative to compound (7).
  • the solvent include 1,4-dioxane, tetrahydrofuran, ethyl acetate and the like.
  • the reaction temperature is usually 0 to 35 ° C., preferably 15 to 25 ° C., and the reaction time is usually 1 to 24 hours.
  • Process 3 In this step, compound (8) and compound (2) are reacted to obtain compound (I). This step is performed by the same method as in step 1 of the manufacturing route (1).
  • Compounds (1), (2), (5) and (6) which are raw material compounds can be commercially available or can be produced by a method known per se.
  • the target compound In each reaction of the target compound and raw material synthesis, when the raw material compound has an amino group, a carboxy group, or a hydroxy group as a substituent, these groups are protected with a protecting group that is generally used in peptide chemistry and the like. It may be. In this case, the target compound can be obtained by removing the protecting group as necessary after the reaction.
  • Examples of the protecting group for amino group include formyl group, C 1-6 alkyl-carbonyl group (acetyl, propionyl, etc.), phenylcarbonyl group, C 1-6 alkyl-oxycarbonyl group (methoxycarbonyl, ethoxycarbonyl, tert- Butoxycarbonyl group, etc.), aryloxycarbonyl group (phenyloxycarbonyl etc.), C 7-10 aralkyl-carbonyl group (benzyloxycarbonyl etc.), benzyl group, benzhydryl group, trityl group, phthaloyl group, etc.
  • the group may have a substituent.
  • substituents include halogen atoms (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups and the like.
  • the number of substituents is about 1 to 3.
  • Examples of the protecting group for the carboxy group include a C 1-6 alkyl group (methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.), a phenyl group, a trityl group, a silyl group, and the like. These protecting groups may have a substituent. Examples of these substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), formyl groups, C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups, etc. The number of substituents is about 1 to 3.
  • Examples of the protecting group for the hydroxy group include C 1-6 alkyl groups (methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.), phenyl groups, C 7-10 aralkyl groups (benzyl, etc.) , Formyl group, C 1-6 alkyl-carbonyl group (acetyl, propionyl etc.), aryloxycarbonyl group (phenyloxycarbonyl etc.), C 7-10 aralkyl-carbonyl group (benzyloxycarbonyl etc.), pyranyl group, furanyl group , A silyl group, and the like, and these protective groups may have a substituent.
  • C 1-6 alkyl groups methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.
  • phenyl groups C 7-10 aralkyl groups (benz
  • substituents examples include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), C 1-6 alkyl groups, phenyl groups, C 7-10 aralkyl groups, nitro groups, and the like.
  • the number of substituents is about 1 to 4.
  • inorganic acid hydrogen chloric acid, sulfuric acid, hydrobromic acid, etc.
  • organic acid methanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid
  • Oxalic acid fumaric acid, maleic acid, tartaric acid, etc.
  • inorganic bases alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, aluminum or ammonium
  • organic bases trimethylamine, triethylamine, pyridine, A salt with picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine or N, N′-dibenzylethylenediamine, etc.
  • the compound when the raw material compound can form a salt, the compound may be used as a salt.
  • a salt for example, those exemplified as the salt of compound (I) are used.
  • the compound (I) of the present invention produced by such a method can be isolated and purified by usual separation means such as recrystallization, distillation, chromatography and the like.
  • compound (I) contains optical isomers, stereoisomers, positional isomers, and rotational isomers, these are also included as compound (I), as well as synthetic methods and separation methods known per se (concentration). , Solvent extraction, column chromatography, recrystallization, etc.), each can be obtained as a single product.
  • compound (I) has an optical isomer
  • the optical isomer resolved from the compound is also encompassed in compound (I).
  • the optical isomer can be produced by a method known per se. Specifically, an optical isomer is obtained by using an optically active synthetic intermediate or by optically resolving the final racemate according to a conventional method.
  • Compound (I) may be a crystal, and it is included in compound (I) regardless of whether the crystal form is a single crystal form or a mixture of crystal forms.
  • the crystal can be produced by crystallization by applying a crystallization method known per se.
  • Compound (I) may be a hydrate, a non-hydrate, a solvate, or a non-solvate.
  • the compound of the present invention has low toxicity and is used as it is or mixed with a pharmacologically acceptable carrier to make a pharmaceutical composition, so that a mammal (eg, human, mouse, rat, rabbit, dog, cat, Cattle, horses, pigs, monkeys) can be used as preventive or therapeutic agents for various diseases described below.
  • a mammal eg, human, mouse, rat, rabbit, dog, cat, Cattle, horses, pigs, monkeys
  • the pharmacologically acceptable carrier various organic or inorganic carrier substances commonly used as pharmaceutical materials are used, and excipients, lubricants, binders, disintegrants in solid preparations; solvents in liquid preparations , Solubilizing agents, suspending agents, isotonic agents, buffers, soothing agents and the like. If necessary, preparation additives such as preservatives, antioxidants, colorants, sweeteners and the like can also be used.
  • excipients include lactose, sucrose, D-mannitol, D-sorbitol, starch, pregelatinized starch, dextrin, crystalline cellulose, low-substituted hydroxypropylcellulose, sodium carboxymethylcellulose, gum arabic, pullulan, light
  • excipients include anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminate metasilicate.
  • lubricant examples include magnesium stearate, calcium stearate, talc and colloidal silica.
  • Preferred examples of the binder include pregelatinized starch, sucrose, gelatin, gum arabic, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, sucrose, D-mannitol, trehalose, dextrin, pullulan, hydroxypropylcellulose, hydroxy Examples include propylmethylcellulose and polyvinylpyrrolidone.
  • disintegrant examples include lactose, sucrose, starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, croscarmellose sodium, carboxymethyl starch sodium, light anhydrous silicic acid, and low-substituted hydroxypropyl cellulose.
  • Suitable examples of the solvent include water for injection, physiological saline, Ringer's solution, alcohol, propylene glycol, polyethylene glycol, sesame oil, corn oil, olive oil, and cottonseed oil.
  • solubilizer examples include polyethylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate. Is mentioned.
  • suspending agent examples include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate; polyvinyl alcohol, polyvinylpyrrolidone , Hydrophilic polymers such as sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose; polysorbates, and polyoxyethylene hydrogenated castor oil.
  • surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate
  • polyvinyl alcohol, polyvinylpyrrolidone Hydrophilic polymers such as sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose,
  • Preferable examples of the isotonic agent include sodium chloride, glycerin, D-mannitol, D-sorbitol and glucose.
  • buffer solutions such as phosphate, acetate, carbonate, citrate.
  • a preferred example of the soothing agent is benzyl alcohol.
  • Preferable examples of the preservative include p-hydroxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid and sorbic acid.
  • Preferable examples of the antioxidant include sulfite and ascorbate.
  • the colorant examples include water-soluble edible tar dyes (eg, edible dyes such as edible red Nos. 2 and 3, edible yellows Nos. 4 and 5, edible blue Nos. 1 and 2, etc.), water-insoluble lake dyes (Eg, the aluminum salt of the water-soluble edible tar dye) and natural dyes (eg, ⁇ -carotene, chlorophyll, bengara).
  • water-soluble edible tar dyes eg, edible dyes such as edible red Nos. 2 and 3, edible yellows Nos. 4 and 5, edible blue Nos. 1 and 2, etc.
  • water-insoluble lake dyes Eg, the aluminum salt of the water-soluble edible tar dye
  • natural dyes eg, ⁇ -carotene, chlorophyll, bengara
  • Suitable examples of sweeteners include saccharin sodium, dipotassium glycyrrhizinate, aspartame, and stevia.
  • Examples of the dosage form of the pharmaceutical composition include tablets (including sugar-coated tablets, film-coated tablets, sublingual tablets, orally disintegrating tablets), capsules (including soft capsules and microcapsules), granules, powders, and lozenges.
  • Oral preparations such as syrup, emulsion, suspension, film (eg, orally disintegrating film); and injection (eg, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, Intravenous preparations, external preparations (eg, transdermal preparations, ointments), suppositories (eg, rectal suppositories, vaginal suppositories), pellets, nasal preparations, pulmonary preparations (inhalants), eye drops, etc. Oral preparations are mentioned. These can be safely administered orally or parenterally (eg, topical, rectal, intravenous administration).
  • compositions may be controlled-release preparations (eg, sustained-release microcapsules) such as immediate-release preparations or sustained-release preparations.
  • the pharmaceutical composition can be produced by a method commonly used in the field of pharmaceutical technology, for example, a method described in the Japanese Pharmacopoeia.
  • the content of the compound of the present invention in the pharmaceutical composition varies depending on the dosage form, the dose of the compound of the present invention, etc., but is, for example, about 0.1 to 100% by weight.
  • an oral preparation When manufacturing an oral preparation, it may be coated for the purpose of taste masking, enteric solubility or sustainability, if necessary.
  • coating base used for coating examples include sugar coating base, water-soluble film coating base, enteric film coating base and sustained-release film coating base.
  • sucrose is used, and one or more selected from talc, precipitated calcium carbonate, gelatin, gum arabic, pullulan, carnauba wax and the like may be used in combination.
  • water-soluble film coating base examples include cellulose polymers such as hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and methylhydroxyethylcellulose; polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer E [Eudragit E (trade name) ], Synthetic polymers such as polyvinylpyrrolidone; polysaccharides such as pullulan.
  • enteric film coating bases include cellulose polymers such as hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, and cellulose acetate phthalate; methacrylic acid copolymer L [Eudragit L (trade name) ] Acrylic acid polymers such as methacrylic acid copolymer LD [Eudragit L-30D55 (trade name)], methacrylic acid copolymer S [Eudragit S (trade name)]; natural products such as shellac.
  • cellulose polymers such as hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, and cellulose acetate phthalate
  • methacrylic acid copolymer L (Eudragit L (trade name) ]
  • Acrylic acid polymers such as methacrylic acid copolymer LD [Eudragit L-30D55 (trade name)], methacrylic acid copolymer
  • sustained-release film coating base examples include cellulose polymers such as ethyl cellulose; aminoalkyl methacrylate copolymer RS [Eudragit RS (trade name)], ethyl acrylate-methyl methacrylate copolymer suspension [Eudragit Acrylic polymer such as NE (trade name)].
  • cellulose polymers such as ethyl cellulose; aminoalkyl methacrylate copolymer RS [Eudragit RS (trade name)], ethyl acrylate-methyl methacrylate copolymer suspension [Eudragit Acrylic polymer such as NE (trade name)].
  • the above-mentioned coating bases may be used by mixing two or more of them in an appropriate ratio. Moreover, you may use light-shielding agents, such as a titanium oxide, ferric oxide, etc. in the case of coating.
  • the compound of the present invention has low toxicity (eg, acute toxicity, chronic toxicity, genotoxicity, reproductive toxicity, cardiotoxicity, carcinogenicity), few side effects, and mammals (eg, humans, cows, horses, dogs, cats, Monkeys, mice, rats) can be used as preventive or therapeutic agents for various diseases or as diagnostic agents.
  • toxicity eg, acute toxicity, chronic toxicity, genotoxicity, reproductive toxicity, cardiotoxicity, carcinogenicity
  • mammals eg, humans, cows, horses, dogs, cats, Monkeys, mice, rats
  • the compound of the present invention has excellent V1b receptor antagonism, and central psychiatric disorders (mood disorders, anxiety disorders, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, epilepsy, etc.) It is useful as a preventive or therapeutic agent.
  • the dose of the compound of the present invention varies depending on the administration subject, administration route, target disease, symptom, etc. For example, when administered orally to an adult bone disease patient, it is usually about 0.01 to 100 mg / kg as a single dose.
  • the body weight is preferably 0.05 to 30 mg / kg body weight, more preferably 0.1 to 10 mg / kg body weight, and it is desirable to administer this amount once to three times a day.
  • Example 2 (1) Synthesis of ethyl 1-[(2-nitrophenoxy) acetyl] -3-piperidinecarboxylate
  • Ethyl 3-piperidinecarboxylate (0.753 g) was dissolved in dichloromethane (25 mL), and o-nitrophenoxyacetic acid (1 .13 g), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.11 g) and 4- (dimethylamino) pyridine (60 mg) were added and stirred at room temperature overnight.
  • the reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and concentrated under reduced pressure.
  • Example 34 (1) Synthesis of [1- (t-butoxycarbonyl) piperidin-3 (S) -yl]-[4- (3-methylphenyl) -3-methylpiperazin-1-yl] methanone (S) —N— t-Butoxycarbonylnipecotic acid (159 mg) was dissolved in dichloromethane (3 mL) to give 1-hydroxybenzotriazole monohydrate (97 mg), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (145 mg) and 2-methyl-1- (m-tolyl) piperazine (120 mg) were added and stirred at 25 ° C. overnight.
  • the following compounds were produced using the corresponding raw materials.
  • the corresponding raw material used a commercial item, or manufactured according to a method known per se.
  • the structural formulas and physicochemical data of the compounds are shown in Table 1.
  • Formulation Example 1 (Manufacture of capsules) 1) Compound of Example 2 30 mg 2) Fine powder cellulose 10 mg 3) Lactose 19 mg 4) Magnesium stearate 1 mg 60 mg total 1), 2), 3) and 4) are mixed and filled into gelatin capsules.
  • Formulation Example 2 Manufacture of tablets
  • Test Example 1 Method for Measuring V1b Receptor Antagonism HEK293 cells stably expressing human V1b receptor were cultured in Dulbecco's modified Eagle medium (4500 mg / L glucose, 10% FBS, containing penicillin / streptomycin) and the day before the test. 30000 cells were seeded per well of a 96 well plate (black transparent bottom, half area). One hour before the measurement, the culture solution was removed and replaced with a buffer solution (1 ⁇ HBSS, 20 mM HEPES pH 7.4), a loading dye solution (FLIPR Calcium 5 assay kit) was added, and the mixture was allowed to stand in a 37 ° C. CO 2 incubator.
  • Dulbecco's modified Eagle medium 4500 mg / L glucose, 10% FBS, containing penicillin / streptomycin
  • the compound of the present invention has an arginine-vasopressin 1b receptor antagonistic action, it has central psychiatric disorders (mood disorders, anxiety disorders, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, epilepsy, etc.) It is useful as a preventive or therapeutic agent for various diseases.

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Description

ピぺラジン誘導体およびその用途Piperazine derivatives and uses thereof

　本発明は、アルギニン－バソプレシン１ｂ（以下Ｖ１ｂともいう）受容体拮抗作用を有し、中枢精神疾患領域（気分障害、不安障害、統合失調症、アルツハイマー病、パーキンソン病、ハンチントン舞踏病、摂食障害、てんかん等）の疾患における予防または治療剤として有用な化合物に関する。 The present invention has an arginine-vasopressin 1b (hereinafter also referred to as V1b) receptor antagonistic action, and has a central psychiatric disorder (mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder) And a compound useful as a prophylactic or therapeutic agent in diseases such as epilepsy.

　Ｖ１ｂ受容体は下垂体後葉からのＡＣＴＨ分泌に関与するほか、脳広域において多様な精神調節の機能を担うと考えられている。Ｖ１ｂ受容体は気分障害、不安障害との関連が示唆されており、Ｖ１ｂ受容体拮抗物質の有用性が研究されている。 V1b receptors are involved in ACTH secretion from the posterior lobe of the pituitary gland, and are thought to be responsible for various psychoregulatory functions throughout the brain. The V1b receptor has been suggested to be associated with mood disorders and anxiety disorders, and the usefulness of V1b receptor antagonists has been studied.

　アルギニン－バソプレシン（ＡＶＰ）は９個のアミノ酸よりなるペプチドで主に視床下部で生合成され、下垂体後葉ホルモンとして、血漿浸透圧、血圧および体液量調節に関与している。また、脳内の広い領域においてその存在が確認されており、精神機能の調節メカニズムに関わる事が示唆されている。ＡＶＰ受容体はＶ１ａ、Ｖ１ｂおよびＶ２受容体の３つのサブタイプがクローニングされており、全て７回膜貫通型受容体である。Ｖ１ｂ受容体は、Ｖ１ａ受容体と同様にＧｑ／１１と共役し、ＰＩ応答を促進する。Ｖ１ｂ受容体は、下垂体に最も多く存在し、ＡＶＰによる下垂体後葉からのＡＣＴＨ分泌に関与している。また、下垂体以外にも脳広域に分布し、海馬、扁桃体、嗅内皮質等の辺縁系、大脳皮質、嗅球、セロトニン神経系の起始核である縫線核にも多く存在する。近年、Ｖ１ｂ受容体と気分障害、不安障害との関連が示唆されており、Ｖ１ｂ受容体拮抗物質の有用性が研究されている。また、Ｖ１ｂ受容体拮抗物質の抗不安様作用や、種々の動物モデルにおいて抗うつおよび抗不安作用を示すことが報告されている。 Arginine-vasopressin (AVP) is a 9-amino acid peptide that is biosynthesized mainly in the hypothalamus and is involved in the regulation of plasma osmotic pressure, blood pressure, and body fluid volume as a pituitary posterior lobe hormone. In addition, its presence has been confirmed in a wide area in the brain, suggesting that it is involved in the mechanism of mental function regulation. The AVP receptor has three subtypes of V1a, V1b and V2 receptors, all of which are 7-transmembrane receptors. The V1b receptor, like the V1a receptor, is coupled to Gq / 11 and promotes the PI response. V1b receptors are most abundant in the pituitary gland and are involved in ATH secretion from the posterior pituitary gland by AVP. In addition to the pituitary gland, it is distributed over a wide area of the brain, and is also present in the limbic system such as the hippocampus, amygdala, and olfactory cortex, the cerebral cortex, the olfactory bulb, and the raphe nucleus, which is the origin of the serotonin nervous system. In recent years, it has been suggested that the V1b receptor is associated with mood disorders and anxiety disorders, and the usefulness of V1b receptor antagonists has been studied. In addition, it has been reported that an anxiolytic-like action of a V1b receptor antagonist and an antidepressant and anxiolytic action in various animal models.

　Ｖ１ｂ受容体拮抗作用を有する化合物として、例えば、特許文献１～１１、非特許文献１～５に記載の化合物が知られているが、本願化合物とは構造が全く異なる。 For example, compounds described in Patent Documents 1 to 11 and Non-Patent Documents 1 to 5 are known as compounds having a V1b receptor antagonistic activity, but the structure is completely different from that of the present compound.

　一方、ニペコタミド誘導体としては、以下の化合物が知られている。 On the other hand, the following compounds are known as nipecotamide derivatives.

Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000006

Figure JPOXMLDOC01-appb-C000007
Figure JPOXMLDOC01-appb-C000007

Figure JPOXMLDOC01-appb-C000008
Figure JPOXMLDOC01-appb-C000008

ＷＯ２００６／１０２３０８WO2006 / 102308 ＷＯ２００６／１３３２４２WO2006 / 133242 ＷＯ２００７／１０９０９８WO2007 / 109098 ＷＯ２００８／０２５７３６WO2008 / 025736 ＷＯ２００８／０３３７５７WO2008 / 033757 ＷＯ２００８／０３３７６４WO2008 / 033764 ＷＯ２００８／０７１７７９WO2008 / 071777 ＷＯ２００９／０１７２３６WO2009 / 017236 ＷＯ２００９／１３０２３１WO2009 / 130231 ＷＯ２００９／１３０２３２WO2009 / 130232 ＷＯ２０１１／０９６４６１WO2011 / 096461

Ｂｉｏｏｒｇａｎｉｃ＆Ｍｅｄｉｃｉｎａｌ　Ｃｈｅｍｉｓｔｒｙ　Ｌｅｔｔｅｒｓ，２０１１，２１（１），９２－９６Bioorganic & Medicinal Chemistry Letters, 2011, 21 (1), 92-96. Ｂｉｏｏｒｇａｎｉｃ＆Ｍｅｄｉｃｉｎａｌ　Ｃｈｅｍｉｓｔｒｙ　Ｌｅｔｔｅｒｓ，２０１１，２１（１２），３６０３－７Bioorganic & Medicinal Chemistry Letters, 2011, 21 (12), 3603-7 Ｂｉｏｏｒｇａｎｉｃ＆Ｍｅｄｉｃｉｎａｌ　Ｃｈｅｍｉｓｔｒｙ　Ｌｅｔｔｅｒｓ，２０１１，２１（１２），３８２８－３８３１Bioorganic & Medicinal Chemistry Letters, 2011, 21 (12), 3828-3831. Ｂｉｏｏｒｇａｎｉｃ＆Ｍｅｄｉｃｉｎａｌ　Ｃｈｅｍｉｓｔｒｙ　Ｌｅｔｔｅｒｓ，２０１０，２０（１８），５３９４－５３９７Bioorganic & Medicinal Chemistry Letters, 2010, 20 (18), 5394-5397 Ｂｉｏｏｒｇａｎｉｃ＆Ｍｅｄｉｃｉｎａｌ　Ｃｈｅｍｉｓｔｒｙ　Ｌｅｔｔｅｒｓ，２００９，１９（２１），６０１８－２２Bioorganic & Medicinal Chemistry Letters, 2009, 19 (21), 6018-22

　本発明の目的は、Ｖ１ｂ受容体拮抗作用を有する化合物を提供することである。 An object of the present invention is to provide a compound having a V1b receptor antagonistic action.

　本発明者らは、上記課題を解決すべく鋭意検討した結果、下記の式で示される化合物が、優れたＶ１ｂ受容体拮抗作用を有することを見出し、本発明を完成するに至った。 As a result of intensive studies aimed at solving the above-mentioned problems, the present inventors have found that a compound represented by the following formula has an excellent V1b receptor antagonistic action, and have completed the present invention.

　すなわち、本発明は以下の通りである。
［１］一般式（Ｉ）： That is, the present invention is as follows.
[1] General formula (I):

Figure JPOXMLDOC01-appb-C000009
Figure JPOXMLDOC01-appb-C000009

（式中、
環Ａは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１は、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよい芳香族複素環基を示す。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、置換されていてもよいＣ６－１４アリール基を示す。）で表される基；
(3) －（ＣＨ２）ｎ－Ｒｚ（式中、Ｒｚは、置換されていてもよいＣ６－１４アリール基を示し、ｎは、１ないし５の整数を示す。）で表される基；
(4) 置換されていてもよいＣ６－１４アリール基；または
(5) 置換されていてもよい縮合環基
を示し；
Ｒ２、Ｒ３、Ｒ４およびＲ５は、それぞれ独立して、水素原子または置換基を示し；
Ｒ６は、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基を示す。）
で表される化合物（以下、化合物（Ｉ）ともいう。）またはその塩を含有する、アルギニン－バソプレシン１ｂ受容体拮抗剤。
［１ａ］一般式（Ｉ）： (Where
Ring A represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1 is
(1) —CH═CH—R x (wherein R x represents an optionally substituted C 6-14 aryl group or an optionally substituted aromatic heterocyclic group). Group;
(2) (wherein, R y represents an optionally substituted C 6-14 aryl group.) -CH 2 -O-R y group represented by;
(3) - (CH 2) n -R z ( wherein, R z is substituted indicates which may C 6-14 aryl group, n is 1 to an integer of 5.) Is represented by Group;
(4) an optionally substituted C 6-14 aryl group; or
(5) represents an optionally substituted fused ring group;
R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom or a substituent;
R 6 is optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show. )
An arginine-vasopressin 1b receptor antagonist comprising a compound represented by formula (hereinafter also referred to as compound (I)) or a salt thereof.
[1a] General formula (I):

Figure JPOXMLDOC01-appb-C000010
Figure JPOXMLDOC01-appb-C000010

（式中、
環Ａは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１は、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、置換されていてもよいＣ６－１４アリール基を示す。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、置換されていてもよいＣ６－１４アリール基を示す。）で表される基；または
(3) 置換されていてもよいＣ６－１４アリール基
を示し；
Ｒ２、Ｒ３、Ｒ４およびＲ５は、それぞれ独立して、水素原子または置換基を示し；
Ｒ６は、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基を示す。）
で表される化合物またはその塩を含有する、アルギニン－バソプレシン１ｂ受容体拮抗剤。 (Where
Ring A represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1 is
(1) -CH = CH-R x (. Wherein, R x is the substituted represents an C 6-14 aryl group) represented by group;
(2) (wherein, R y represents an optionally substituted C 6-14 aryl group.) -CH 2 -O-R y group represented by; or
(3) represents an optionally substituted C 6-14 aryl group;
R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom or a substituent;
R 6 is optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show. )
An arginine-vasopressin 1b receptor antagonist comprising a compound represented by the formula:

［２］一般式（Ｉａ）： [2] General formula (Ia):

Figure JPOXMLDOC01-appb-C000011
Figure JPOXMLDOC01-appb-C000011

（式中、
環Ａａは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ａは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよい芳香族複素環基を示し；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つは置換基を示し、かつ残りは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ａは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよいＣ７－１６アラルキル基を示す。）
で表される化合物（以下、化合物（Ｉａ）ともいう。）またはその塩。
［２ａ］一般式（Ｉａ）： (Where
Ring Aa represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1a represents an optionally substituted C 6-14 aryl group, or an optionally substituted aromatic heterocyclic group;
At least one of R 2a , R 3a , R 4a and R 5a represents a substituent, and the rest each independently represents a hydrogen atom or a substituent;
R 6a represents an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group. )
Or a salt thereof (hereinafter also referred to as compound (Ia)).
[2a] General formula (Ia):

Figure JPOXMLDOC01-appb-C000012
Figure JPOXMLDOC01-appb-C000012

（式中、
環Ａａは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ａは、置換されていてもよいＣ６－１４アリール基を示し；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つは置換基を示し、かつ残りは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ａは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよいＣ７－１６アラルキル基を示す。）
で表される化合物またはその塩。
［３］Ｒ１ａが、ニトロ基でそれぞれ置換されていてもよい、Ｃ６－１０アリール基または５または６員の単環式芳香族複素環基である、上記［２］記載の化合物またはその塩。
［３ａ］Ｒ１ａが、ニトロ基で置換されていてもよいＣ６－１０アリール基である、上記［２ａ］記載の化合物またはその塩。
［４］Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの１つがＣ１－６アルキル基であり、かつ残り３つが水素原子である、上記［２］または［２ａ］記載の化合物またはその塩。
［５］Ｒ６ａが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基、またはＣ７－１３アラルキル基である、上記［２］または［２ａ］記載の化合物またはその塩。
［６］環Ａａが、Ｃ１－６アルキル基でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環である、上記［２］または［２ａ］記載の化合物またはその塩。 (Where
Ring Aa represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1a represents an optionally substituted C 6-14 aryl group;
At least one of R 2a , R 3a , R 4a and R 5a represents a substituent, and the rest each independently represents a hydrogen atom or a substituent;
R 6a represents an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group. )
Or a salt thereof.
[3] The compound according to the above [2] or a compound thereof, wherein R 1a is a C 6-10 aryl group or a 5- or 6-membered monocyclic aromatic heterocyclic group, each optionally substituted with a nitro group salt.
[3a] The compound according to the above [2a] or a salt thereof, wherein R 1a is a C 6-10 aryl group optionally substituted with a nitro group.
[4] The compound or a salt thereof according to the above [2] or [2a], wherein one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group, and the remaining three are hydrogen atoms.
[5] The compound according to [2] or [2a] above, wherein R 6a is a C 6-10 aryl group optionally substituted with a C 1-6 alkyl group, or a C 7-13 aralkyl group, or a compound thereof salt.
[6] The compound according to the above [2] or [2a] or a salt thereof, wherein the ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group.

［７］一般式（Ｉｂ）： [7] General formula (Ib):

Figure JPOXMLDOC01-appb-C000013
Figure JPOXMLDOC01-appb-C000013

（式中、
環Ａｂは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ｂは、
(1) ニトロ基およびＣ１－６アルコキシ基で置換されたＣ６－１４アリール基、
(2) 置換されていてもよいベンゾフリル、または
(3) 置換されていてもよいインダニル
を示し；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ｂは、置換されていてもよいＣ６－１４アリール基を示す。）
で表される化合物（以下、化合物（Ｉｂ）ともいう。）またはその塩。
［７ａ］一般式（Ｉｂ）： (Where
Ring Ab represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1b is
(1) a C 6-14 aryl group substituted with a nitro group and a C 1-6 alkoxy group,
(2) optionally substituted benzofuryl, or
(3) represents an optionally substituted indanyl;
R 2b , R 3b , R 4b and R 5b each independently represent a hydrogen atom or a substituent;
R 6b represents an optionally substituted C 6-14 aryl group. )
Or a salt thereof (hereinafter also referred to as compound (Ib)).
[7a] General formula (Ib):

Figure JPOXMLDOC01-appb-C000014
Figure JPOXMLDOC01-appb-C000014

（式中、
環Ａｂは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ｂは、ニトロ基およびＣ１－６アルコキシ基で置換されたＣ６－１４アリール基を示し；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ｂは、置換されていてもよいＣ６－１４アリール基を示す。）
で表される化合物またはその塩。
［８］Ｒ１ｂが、
(1) １個のニトロ基と１または２個のＣ１－６アルコキシ基で置換されたＣ６－１０アリール基、
(2) ベンゾフリル、または
(3) インダニル
である、上記［７］記載の化合物またはその塩。
［８ａ］Ｒ１ｂが、１個のニトロ基と１または２個のＣ１－６アルコキシ基で置換されたＣ６－１０アリール基である、上記［７ａ］記載の化合物またはその塩。
［９］Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つがＣ１－６アルキル基であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基である、上記［７］または［７ａ］記載の化合物またはその塩。
［１０］Ｒ６ｂが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基である、上記［７］または［７ａ］記載の化合物またはその塩。
［１１］環Ａｂが、Ｃ１－６アルキル基で置換されていてもよいピペリジン環である、上記［７］または［７ａ］記載の化合物またはその塩。 (Where
Ring Ab represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1b represents a C 6-14 aryl group substituted with a nitro group and a C 1-6 alkoxy group;
R 2b , R 3b , R 4b and R 5b each independently represent a hydrogen atom or a substituent;
R 6b represents an optionally substituted C 6-14 aryl group. )
Or a salt thereof.
[8] R 1b is
(1) a C 6-10 aryl group substituted with one nitro group and one or two C 1-6 alkoxy groups,
(2) benzofuryl, or
(3) The compound or a salt thereof according to the above [7], which is indanyl.
[8a] The compound or a salt thereof according to the above [7a], wherein R 1b is a C 6-10 aryl group substituted with one nitro group and one or two C 1-6 alkoxy groups.
[9] The above item , wherein at least one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group, and the rest are each independently a hydrogen atom or a C 1-6 alkyl group [ 7] or [7a] or a salt thereof.
[10] The compound or a salt thereof according to the above [7] or [7a], wherein R 6b is a C 6-10 aryl group optionally substituted with a C 1-6 alkyl group.
[11] The compound or a salt thereof according to the above [7] or [7a], wherein the ring Ab is a piperidine ring optionally substituted with a C 1-6 alkyl group.

［１２］一般式（Ｉｃ）： [12] General formula (Ic):

Figure JPOXMLDOC01-appb-C000015
Figure JPOXMLDOC01-appb-C000015

（式中、
環Ａｃは、５ないし７員含窒素飽和複素環を示し；
Ｒ１ｃは、置換されていてもよいＣ６－１４アリール基を示し；
Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ｃは、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基を示す。）
で表される化合物（以下、化合物（Ｉｃ）ともいう。）またはその塩。
［１３］Ｒ１ｃが、ニトロ基で置換されていてもよいＣ６－１０アリール基である、上記［１２］記載の化合物またはその塩。
［１４］Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの少なくとも１つがＣ１－６アルキル基であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基である、上記［１２］記載の化合物またはその塩。
［１５］Ｒ６ｃが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基、Ｃ１－６アルキル基で置換されていてもよいＣ７－１６アラルキル基、またはＣ６－１０アリール－Ｃ２－６アルケニル基である、上記［１２］記載の化合物またはその塩。
［１６］環Ａｃが、ピペリジン環である、上記［１２］記載の化合物またはその塩。 (Where
Ring Ac represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1c represents an optionally substituted C 6-14 aryl group;
R 2c , R 3c , R 4c and R 5c each independently represent a hydrogen atom or a substituent;
R 6c is an optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show. )
Or a salt thereof (hereinafter also referred to as compound (Ic)).
[13] The compound of the above-mentioned [12] or a salt thereof, wherein R 1c is a C 6-10 aryl group optionally substituted with a nitro group.
[14] The above, wherein at least one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group, and the rest are each independently a hydrogen atom or a C 1-6 alkyl group [ 12] The compound or a salt thereof according to [12].
[15] R 6c is, C 1-6 alkyl group optionally substituted C 6-10 aryl group, C 1-6 alkyl optionally substituted C 7-16 aralkyl group, or a group C 6, The compound or a salt thereof according to the above [12], which is a -10 aryl-C 2-6 alkenyl group.
[16] The compound of the above-mentioned [12] or a salt thereof, wherein the ring Ac is a piperidine ring.

［１７］一般式（Ｉｄ）： [17] General formula (Id):

Figure JPOXMLDOC01-appb-C000016
Figure JPOXMLDOC01-appb-C000016

（式中、
環Ａｄは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ｄは、置換されていてもよいＣ６－１４アリール基を示し；
Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの少なくとも１つは置換基を示し、かつ残りは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ｄは、置換されていてもよいＣ６－１４アリール基を示し；
ｎｄは、１ないし５の整数を示す。）
で表される化合物（以下、化合物（Ｉｄ）ともいう。）またはその塩。
［１８］Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの１つがＣ１－６アルキル基であり、かつ残り３つが水素原子である、上記［１７］記載の化合物またはその塩。
［１９］Ｒ６ｄが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基である、上記［１７］記載の化合物またはその塩。
［２０］環Ａｄが、ピペリジン環である、上記［１７］記載の化合物またはその塩。
［２１］ｎｄが、１ないし３の整数である、上記［１７］記載の化合物またはその塩。 (Where
Ring Ad represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1d represents an optionally substituted C 6-14 aryl group;
At least one of R 2d , R 3d , R 4d and R 5d represents a substituent, and the rest each independently represents a hydrogen atom or a substituent;
R 6d represents an optionally substituted C 6-14 aryl group;
n d represents an integer of 1 to 5. )
Or a salt thereof (hereinafter also referred to as compound (Id)).
[18] The compound of the above-mentioned [17] or a salt thereof, wherein one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group, and the remaining three are hydrogen atoms.
[19] The compound of the above-mentioned [17] or a salt thereof, wherein R 6d is a C 6-10 aryl group optionally substituted with a C 1-6 alkyl group.
[20] The compound of the above-mentioned [17] or a salt thereof, wherein the ring Ad is a piperidine ring.
[21] n d is an integer of 1 to 3, the [17] or a salt thereof.

［２２］上記［２］ないし［２１］のいずれかに記載の化合物またはその塩、および医薬上許容される担体を含有する医薬組成物。
［２３］上記［１］ないし［２１］のいずれかに記載の化合物またはその塩を含有する、気分障害、不安障害、統合失調症、アルツハイマー病、パーキンソン病、ハンチントン舞踏病、摂食障害またはてんかんの予防または治療剤。 [22] A pharmaceutical composition comprising the compound according to any one of [2] to [21] above or a salt thereof, and a pharmaceutically acceptable carrier.
[23] Mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder or epilepsy, containing the compound or salt thereof according to any one of [1] to [21] above Preventive or therapeutic agent.

　化合物（Ｉ）は、Ｖ１ｂ受容体拮抗作用を有することより、中枢精神疾患領域（気分障害、不安障害、統合失調症、アルツハイマー病、パーキンソン病、ハンチントン舞踏病、摂食障害、てんかん等）の疾患における予防または治療剤として有用である。 Compound (I) has a V1b receptor antagonism, and thus has a central psychiatric disorder (mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, epilepsy, etc.) It is useful as a preventive or therapeutic agent.

発明の実施の形態BEST MODE FOR CARRYING OUT THE INVENTION

　以下、式中の各記号の定義について詳述する。
　本明細書中の「ハロゲン原子」としては、フッ素原子、塩素原子、臭素原子およびヨウ素原子が挙げられる。
　本明細書中の「置換基」としては、「置換されていてもよい炭化水素基」、「置換されていてもよい複素環基」、「置換されていてもよいヒドロキシ基」、「置換されていてもよいアミノ基」、「置換されていてもよいスルファニル基」、「アシル基」、「ハロゲン原子」、「シアノ基」、「ニトロ基」等が挙げられる。 Hereinafter, the definition of each symbol in the formula will be described in detail.
Examples of the “halogen atom” in the present specification include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
As used herein, “substituent” includes “optionally substituted hydrocarbon group”, “optionally substituted heterocyclic group”, “optionally substituted hydroxy group”, “substituted” And optionally substituted amino group, “optionally substituted sulfanyl group”, “acyl group”, “halogen atom”, “cyano group”, “nitro group” and the like.

　本明細書中の「置換されていてもよい炭化水素基」としては、例えば、「置換されていてもよいＣ１－１０アルキル基」、「置換されていてもよいＣ２－１０アルケニル基」、「置換されていてもよいＣ２－１０アルキニル基」、「置換されていてもよいＣ３－１０シクロアルキル基」、「置換されていてもよいＣ３－１０シクロアルケニル基」、「置換されていてもよいＣ４－１０シクロアルカジエニル基」、「置換されていてもよいＣ６－１４アリール基」、「置換されていてもよいＣ７－１６アラルキル基」、「置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基」等が挙げられる。 Examples of the “optionally substituted hydrocarbon group” in the present specification include “an optionally substituted C 1-10 alkyl group” and “an optionally substituted C 2-10 alkenyl group”. , “Optionally substituted C 2-10 alkynyl group”, “ optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “substituted Optionally substituted C 4-10 cycloalkadienyl group ”,“ optionally substituted C 6-14 aryl group ”,“ optionally substituted C 7-16 aralkyl group ”,“ substituted ” An optionally substituted C 6-10 aryl-C 2-6 alkenyl group ”.

　本明細書中の「Ｃ１－１０アルキル基」としては、例えば、メチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、ｓｅｃ－ブチル、ｔｅｒｔ－ブチル、ペンチル、イソペンチル、ネオペンチル、１－エチルプロピル、ヘキシル、イソヘキシル、１，１－ジメチルブチル、２，２－ジメチルブチル、３，３－ジメチルブチル、２－エチルブチル、ヘプチル、オクチル、ノニル、デシル等が挙げられる。なかでも、Ｃ１－６アルキル基が好ましい。
　本明細書中の「Ｃ１－６アルキル（基）」としては、例えば、メチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、ｓｅｃ－ブチル、ｔｅｒｔ－ブチル、ペンチル、イソペンチル、ネオペンチル、１－エチルプロピル、ヘキシル、イソヘキシル、１，１－ジメチルブチル、２，２－ジメチルブチル、３，３－ジメチルブチル、２－エチルブチル等が挙げられる。 Examples of the “C 1-10 alkyl group” in the present specification include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl and hexyl. , Isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, octyl, nonyl, decyl and the like. Of these, a C 1-6 alkyl group is preferable.
Examples of the “C 1-6 alkyl (group)” in the present specification include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl. Hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl and the like.

　本明細書中の「Ｃ２－１０アルケニル基」としては、例えば、エテニル、１－プロペニル、２－プロペニル、２－メチル－１－プロペニル、１－ブテニル、２－ブテニル、３－ブテニル、３－メチル－２－ブテニル、１－ペンテニル、２－ペンテニル、３－ペンテニル、４－ペンテニル、４－メチル－３－ペンテニル、１－ヘキセニル、３－ヘキセニル、５－ヘキセニル、１－ヘプテニル、１－オクテニル等が挙げられる。なかでも、Ｃ２－６アルケニル基が好ましい。
　本明細書中の「Ｃ２－６アルケニル（基）」としては、例えば、エテニル、１－プロペニル、２－プロペニル、２－メチル－１－プロペニル、１－ブテニル、２－ブテニル、３－ブテニル、３－メチル－２－ブテニル、１－ペンテニル、２－ペンテニル、３－ペンテニル、４－ペンテニル、４－メチル－３－ペンテニル、１－ヘキセニル、３－ヘキセニル、５－ヘキセニル等が挙げられる。 Examples of the “C 2-10 alkenyl group” in the present specification include ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3- Methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, 5-hexenyl, 1-heptenyl, 1-octenyl, etc. Is mentioned. Of these, a C 2-6 alkenyl group is preferable.
Examples of the “C 2-6 alkenyl (group)” in the present specification include ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, Examples include 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, 5-hexenyl and the like.

　本明細書中の「Ｃ２－１０アルキニル基」としては、例えば、エチニル、１－プロピニル、２－プロピニル、１－ブチニル、２－ブチニル、３－ブチニル、１－ペンチニル、２－ペンチニル、３－ペンチニル、４－ペンチニル、１－ヘキシニル、２－ヘキシニル、３－ヘキシニル、４－ヘキシニル、５－ヘキシニル、１－ヘプチニル、１－オクチニル等が挙げられる。なかでも、Ｃ２－６アルキニル基が好ましい。
　本明細書中の「Ｃ２－６アルキニル（基）」としては、例えば、エチニル、１－プロピニル、２－プロピニル、１－ブチニル、２－ブチニル、３－ブチニル、１－ペンチニル、２－ペンチニル、３－ペンチニル、４－ペンチニル、１－ヘキシニル、２－ヘキシニル、３－ヘキシニル、４－ヘキシニル、５－ヘキシニル等が挙げられる。 Examples of the “C 2-10 alkynyl group” in the present specification include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3- Examples include pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-heptynyl, 1-octynyl and the like. Of these, a C 2-6 alkynyl group is preferable.
Examples of the “C 2-6 alkynyl (group)” in the present specification include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, Examples include 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl and the like.

　本明細書中の「Ｃ３－１０シクロアルキル基」としては、例えば、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル、シクロオクチル、シクロノニル、シクロデシル等が挙げられる。なかでも、Ｃ３－６シクロアルキル基が好ましい。
　本明細書中の「Ｃ３－８シクロアルキル（基）」としては、例えば、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル、シクロオクチル等が挙げられる。なかでも、Ｃ３－６シクロアルキル基が好ましい。 Examples of the “C 3-10 cycloalkyl group” in the present specification include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and the like. Of these, a C 3-6 cycloalkyl group is preferable.
Examples of the “C 3-8 cycloalkyl (group)” in the present specification include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. Of these, a C 3-6 cycloalkyl group is preferable.

　本明細書中の「Ｃ３－１０シクロアルケニル基」としては、例えば、２－シクロペンテン－１－イル、３－シクロペンテン－１－イル、２－シクロヘキセン－１－イル、３－シクロヘキセン－１－イル等が挙げられる。なかでも、Ｃ３－６シクロアルケニル基が好ましい。
　本明細書中の「Ｃ３－８シクロアルケニル（基）」としては、例えば、２－シクロペンテン－１－イル、３－シクロペンテン－１－イル、２－シクロヘキセン－１－イル、３－シクロヘキセン－１－イル等が挙げられる。なかでも、Ｃ３－６シクロアルケニル基が好ましい。 Examples of the “C 3-10 cycloalkenyl group” in the present specification include 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl and 3-cyclohexen-1-yl. Etc. Of these, a C 3-6 cycloalkenyl group is preferable.
As used herein, “C 3-8 cycloalkenyl (group)” includes, for example, 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexene-1 -Yl and the like. Of these, a C 3-6 cycloalkenyl group is preferable.

　本明細書中の「Ｃ４－１０シクロアルカジエニル基」としては、例えば、２，４－シクロペンタジエン－１－イル、２，４－シクロヘキサジエン－１－イル、２，５－シクロヘキサジエン－１－イル等が挙げられる。なかでも、Ｃ４－６シクロアルカジエニル基が好ましい。
　本明細書中の「Ｃ４－８シクロアルカジエニル（基）」としては、例えば、２，４－シクロペンタジエン－１－イル、２，４－シクロヘキサジエン－１－イル、２，５－シクロヘキサジエン－１－イル等が挙げられる。なかでも、Ｃ４－６シクロアルカジエニル基が好ましい。 Examples of the “C 4-10 cycloalkadienyl group” in the present specification include 2,4-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadiene- 1-yl and the like can be mentioned. Of these, a C 4-6 cycloalkadienyl group is preferable.
As used herein, “C 4-8 cycloalkadienyl (group)” includes, for example, 2,4-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl, 2,5-cyclo And hexadien-1-yl. Of these, a C 4-6 cycloalkadienyl group is preferable.

　上記の「Ｃ３－１０シクロアルキル基」、「Ｃ３－１０シクロアルケニル基」および「Ｃ４－１０シクロアルカジエニル基」は、それぞれベンゼン環と縮合して縮合環基を形成していてもよく、このような縮合環基としては、例えば、インダニル、ジヒドロナフチル、テトラヒドロナフチル、フルオレニル等が挙げられる。 The above “C 3-10 cycloalkyl group”, “C 3-10 cycloalkenyl group” and “C 4-10 cycloalkadienyl group” are each condensed with a benzene ring to form a condensed ring group. Examples of such a condensed ring group include indanyl, dihydronaphthyl, tetrahydronaphthyl, fluorenyl and the like.

　本明細書中の「Ｃ６－１４アリール（基）」としては、例えば、フェニル、ナフチル、アントリル、フェナントリル、アセナフチレニル、ビフェニリル等が挙げられる。また、「Ｃ６－１４アリール（基）」は他の環と縮合していてもよく、例えば、フルオレニル、ジヒドロナフチル、テトラヒドロナフチル等が挙げられる。なかでも、Ｃ６－１０アリール基が好ましい。 Examples of the “C 6-14 aryl (group)” in the present specification include phenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl, biphenylyl and the like. The “C 6-14 aryl (group)” may be condensed with another ring, and examples thereof include fluorenyl, dihydronaphthyl, tetrahydronaphthyl and the like. Of these, a C 6-10 aryl group is preferable.

　本明細書中の「Ｃ７－１６アラルキル（基）」としては、例えば、ベンジル、フェネチル、ナフチルメチル、ビフェニリルメチル等が挙げられる。なかでも、Ｃ７－１３アラルキル基が好ましい。 Examples of the “C 7-16 aralkyl (group)” in the present specification include benzyl, phenethyl, naphthylmethyl, biphenylylmethyl and the like. Of these, a C 7-13 aralkyl group is preferable.

　本明細書中の「Ｃ６－１０アリール－Ｃ２－６アルケニル基」としては、例えば、スチリル、３－フェニル－２－プロペニル等が挙げられる。なかでも、Ｃ６－１０アリール－Ｃ２－４アルケニル基が好ましい。 Examples of the “C 6-10 aryl-C 2-6 alkenyl group” in the present specification include styryl, 3-phenyl-2-propenyl and the like. Of these, a C 6-10 aryl-C 2-4 alkenyl group is preferable.

　本明細書中の「Ｃ１－６アルコキシ（基）」としては、例えば、メトキシ、エトキシ、プロポキシ、イソプロポキシ、ブトキシ、イソブトキシ、ｓｅｃ－ブトキシ、ｔｅｒｔ－ブトキシ等が挙げられる。 Examples of the “C 1-6 alkoxy (group)” in the present specification include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy and the like.

　本明細書中の「複素環（基）」としては、芳香族複素環基および非芳香族複素環基が挙げられる。
　本明細書中の「芳香族複素環基」としては、例えば、環構成原子として炭素原子以外に酸素原子、硫黄原子および窒素原子から選ばれるヘテロ原子を１ないし４個含有する４ないし７員（好ましくは５または６員）の単環式芳香族複素環基および縮合芳香族複素環基（好ましくは８ないし１２員のもの）が挙げられる。該縮合芳香族複素環基としては、例えば、これら４ないし７員の単環式芳香族複素環基に対応する環と、１または２個の窒素原子を含む５または６員の芳香族複素環（例、ピロール、イミダゾール、ピラゾール、ピラジン、ピリジン、ピリミジン）、１個の硫黄原子を含む５員の芳香族複素環（例、チオフェン）およびベンゼン環から選ばれる１または２個が縮合した環から誘導される基等が挙げられる。 Examples of the “heterocycle (group)” in the present specification include an aromatic heterocyclic group and a non-aromatic heterocyclic group.
Examples of the “aromatic heterocyclic group” in the present specification include 4 to 7-membered (containing 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom in addition to a carbon atom as a ring-constituting atom ( And preferably monocyclic aromatic heterocyclic groups and condensed aromatic heterocyclic groups (preferably those having 8 to 12 members). Examples of the condensed aromatic heterocyclic group include a ring corresponding to the 4- to 7-membered monocyclic aromatic heterocyclic group and a 5- or 6-membered aromatic heterocyclic ring containing 1 or 2 nitrogen atoms. (Eg, pyrrole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine) From a ring in which 1 or 2 selected from a 5-membered aromatic heterocycle containing one sulfur atom (eg, thiophene) and a benzene ring are condensed Examples include groups to be derived.

　芳香族複素環基の好適な例としては、
フリル、チエニル、ピリジル、ピリミジニル、ピリダジニル、ピラジニル、ピロリル、イミダゾリル、ピラゾリル、チアゾリル、イソチアゾリル、オキサゾリル、イソオキサゾリル、オキサジアゾリル、チアジアゾリル、トリアゾリル、テトラゾリル、トリアジニル等の単環式芳香族複素環基；
キノリル、イソキノリル、キナゾリル、キノキサリル、ベンゾフリル、ベンゾチエニル、ベンズオキサゾリル、ベンズイソオキサゾリル、ベンゾチアゾリル、ベンズイミダゾリル、ベンゾトリアゾリル、インドリル、インダゾリル、カルバゾリル、ピロロピラジニル、イミダゾピリジル、チエノピリジニル、イミダゾピラジニル、ピラゾロピリジニル、ピラゾロチエニル、ピラゾロトリアジニル、ピリドピリジル、チエノピリジル等の縮合芳香族複素環基；
等が挙げられる。 As preferable examples of the aromatic heterocyclic group,
Monocyclic aromatic heterocyclic groups such as furyl, thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl;
Quinolyl, isoquinolyl, quinazolyl, quinoxalyl, benzofuryl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzimidazolyl, benzotriazolyl, indolyl, indazolyl, carbazolyl, pyrrolopyrazinyl, imidazopyridyl, thienopyridinyl, imidazopyridinyl Condensed aromatic heterocyclic groups such as ru, pyrazolopyridinyl, pyrazolothienyl, pyrazolotriazinyl, pyridopyridyl, thienopyridyl;
Etc.

　本明細書中の「非芳香族複素環基」としては、例えば、環構成原子として炭素原子以外に酸素原子、硫黄原子および窒素原子から選ばれるヘテロ原子を１ないし４個含有する４ないし７員（好ましくは５または６員）の単環式非芳香族複素環基、および縮合非芳香族複素環基（好ましくは８ないし１２員のもの）が挙げられる。該縮合非芳香族複素環基としては、例えば、これら４ないし７員の単環式非芳香族複素環基に対応する環と、１または２個の窒素原子を含む５または６員の芳香族複素環（例、ピロール、イミダゾール、ピラゾール、ピラジン、ピリジン、ピリミジン）、１個の硫黄原子を含む５員の芳香族複素環（例、チオフェン）およびベンゼン環から選ばれる１または２個の環が縮合した環から誘導される基、ならびに該基の部分飽和により得られる基等が挙げられる。 Examples of the “non-aromatic heterocyclic group” in the present specification include 4 to 7 members containing 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom in addition to a carbon atom as a ring constituent atom. (Preferably 5 or 6 membered) monocyclic non-aromatic heterocyclic group and condensed non-aromatic heterocyclic group (preferably having 8 to 12 members). Examples of the condensed non-aromatic heterocyclic group include a ring corresponding to the 4- to 7-membered monocyclic non-aromatic heterocyclic group, and a 5- or 6-membered aromatic containing 1 or 2 nitrogen atoms. 1 or 2 rings selected from a heterocycle (eg, pyrrole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine), a 5-membered aromatic heterocycle containing one sulfur atom (eg, thiophene) and a benzene ring Examples thereof include a group derived from a condensed ring and a group obtained by partial saturation of the group.

　非芳香族複素環基の好適な例としては、
アゼチジニル、ピロリジニル、ピペリジル、モルホリニル、チオモルホリニル、ピペラジニル、ヘキサメチレンイミニル、オキサゾリジニル、チアゾリジニル、イミダゾリジニル、オキサゾリニル、チアゾリニル、イミダゾリニル、ジオキソリル、ジオキソラニル、ジヒドロオキサジアゾリル、ピラニル、テトラヒドロピラニル、チオピラニル、テトラヒドロチオピラニル、テトラヒドロフリル、ピラゾリジニル、ピラゾリニル、テトラヒドロピリミジニル、ジヒドロトリアゾリル、テトラヒドロトリアゾリル等の単環式非芳香族複素環基；
ジヒドロインドリル、ジヒドロイソインドリル、ジヒドロベンゾフラニル、ジヒドロベンゾジオキシニル、ジヒドロベンゾジオキセピニル、テトラヒドロベンゾフラニル、クロメニル、ジヒドロクロメニル、ジヒドロキノリル、テトラヒドロキノリル、ジヒドロイソキノリル、テトラヒドロイソキノリル、ジヒドロフタラジニル等の縮合非芳香族複素環基；等が挙げられる。 As a suitable example of a non-aromatic heterocyclic group,
Azetidinyl, pyrrolidinyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, hexamethyleneiminyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, oxazolinyl, thiazolinyl, imidazolinyl, dioxolyl, dioxolanyl, dihydrooxadiazolyl, thiol, pyranyl Monocyclic non-aromatic heterocyclic groups such as tetrahydrofuryl, pyrazolidinyl, pyrazolinyl, tetrahydropyrimidinyl, dihydrotriazolyl, tetrahydrotriazolyl;
Dihydroindolyl, dihydroisoindolyl, dihydrobenzofuranyl, dihydrobenzodioxinyl, dihydrobenzodioxepinyl, tetrahydrobenzofuranyl, chromenyl, dihydrochromenyl, dihydroquinolyl, tetrahydroquinolyl, dihydroisoquinolyl , Condensed non-aromatic heterocyclic groups such as tetrahydroisoquinolyl and dihydrophthalazinyl; and the like.

　本明細書中の「縮合環基」としては、例えば、縮合芳香族複素環基（好ましくは８ないし１２員のもの）、縮合非芳香族複素環基（好ましくは８ないし１２員のもの）、縮合Ｃ１０－１４アリール基および縮合非芳香族炭化水素基（好ましくは８ないし１２員のもの）が挙げられる。
　該「縮合芳香族複素環基」および「縮合非芳香族複素環基」としては、上記の「縮合芳香族複素環基」および「縮合非芳香族複素環基」が挙げられる。
　該「縮合Ｃ１０－１４アリール基」としては、例えば、上記の「Ｃ６－１４アリール基」のうち、炭素数が１０～１４個の縮合環から誘導される基が挙げられる。
　該「縮合非芳香族炭化水素基」としては、例えば、上記の「Ｃ３－１０シクロアルキル基」、「Ｃ３－１０シクロアルケニル基」および「Ｃ４－１０シクロアルカジエニル基」のうちベンゼン環と縮合したものが挙げられる。 As the “fused ring group” in the present specification, for example, a condensed aromatic heterocyclic group (preferably 8 to 12-membered), a condensed non-aromatic heterocyclic group (preferably 8 to 12-membered), Examples thereof include a condensed C 10-14 aryl group and a condensed non-aromatic hydrocarbon group (preferably having 8 to 12 members).
Examples of the “fused aromatic heterocyclic group” and “fused non-aromatic heterocyclic group” include the above-mentioned “fused aromatic heterocyclic group” and “fused non-aromatic heterocyclic group”.
Examples of the “fused C 10-14 aryl group” include a group derived from a condensed ring having 10 to 14 carbon atoms in the above “C 6-14 aryl group”.
Examples of the “condensed non-aromatic hydrocarbon group” include the above-mentioned “C 3-10 cycloalkyl group”, “C 3-10 cycloalkenyl group” and “C 4-10 cycloalkadienyl group”. Examples thereof include those condensed with a benzene ring.

　縮合環基の好適な例としては、
キノリル、イソキノリル、キナゾリル、キノキサリル、ベンゾフリル、ベンゾチエニル、ベンズオキサゾリル、ベンズイソオキサゾリル、ベンゾチアゾリル、ベンズイミダゾリル、ベンゾトリアゾリル、インドリル、インダゾリル、カルバゾリル、ピロロピラジニル、イミダゾピリジル、チエノピリジニル、イミダゾピラジニル、ピラゾロピリジル、ピラゾロチエニル、ピラゾロトリアジニル、ピリドピリジニル、チエノピリジル等の縮合芳香族複素環基；
ジヒドロインドリル、ジヒドロイソインドリル、ジヒドロベンゾフラニル、ジヒドロベンゾジオキシニル、ジヒドロベンゾジオキセピニル、テトラヒドロベンゾフラニル、クロメニル、ジヒドロクロメニル、ジヒドロキノリル、テトラヒドロキノリル、ジヒドロイソキノリル、テトラヒドロイソキノリル、ジヒドロフタラジニル等の縮合非芳香族複素環基；
ナフチル、アントリル、フェナントリル、アセナフチレニル等の縮合Ｃ１０－１４アリール基；
インダニル、インデニル、ジヒドロナフチル、テトラヒドロナフチル等の縮合非芳香族炭化水素基；等が挙げられる。 As a suitable example of the fused ring group,
Quinolyl, isoquinolyl, quinazolyl, quinoxalyl, benzofuryl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzimidazolyl, benzotriazolyl, indolyl, indazolyl, carbazolyl, pyrrolopyrazinyl, imidazopyridyl, thienopyridinyl, imidazopyridinyl Condensed aromatic heterocyclic groups such as ru, pyrazolopyridyl, pyrazolothienyl, pyrazolotriazinyl, pyridopyridinyl, thienopyridyl;
Dihydroindolyl, dihydroisoindolyl, dihydrobenzofuranyl, dihydrobenzodioxinyl, dihydrobenzodioxepinyl, tetrahydrobenzofuranyl, chromenyl, dihydrochromenyl, dihydroquinolyl, tetrahydroquinolyl, dihydroisoquinolyl Condensed non-aromatic heterocyclic groups such as tetrahydroisoquinolyl and dihydrophthalazinyl;
Condensed C 10-14 aryl groups such as naphthyl, anthryl, phenanthryl, acenaphthylenyl;
And condensed non-aromatic hydrocarbon groups such as indanyl, indenyl, dihydronaphthyl and tetrahydronaphthyl;

　本明細書中の「５ないし７員含窒素飽和複素環」としては、例えば、環構成原子として炭素原子以外に少なくとも１個の窒素原子を含み、さらに酸素原子、硫黄原子および窒素原子から選ばれるヘテロ原子を１ないし２個含有していてもよい５ないし７員の含窒素飽和複素環が挙げられる。該含窒素飽和複素環の例としては、ピロリジン、イミダゾリジン、ピラゾリジン、オキサゾリジン、チアゾリジン、ピペリジン、ピペラジン、アゼパン、モルホリン、チオモルホリン等が挙げられ、なかでも、ピロリジン、ピペリジンおよびアゼパンが好ましい。 The “5- to 7-membered nitrogen-containing saturated heterocyclic ring” in the present specification includes, for example, at least one nitrogen atom in addition to a carbon atom as a ring constituent atom, and is further selected from an oxygen atom, a sulfur atom and a nitrogen atom. Examples thereof include a 5- to 7-membered nitrogen-containing saturated heterocyclic ring which may contain 1 to 2 heteroatoms. Examples of the nitrogen-containing saturated heterocyclic ring include pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, thiazolidine, piperidine, piperazine, azepane, morpholine, thiomorpholine, and among them, pyrrolidine, piperidine and azepane are preferable.

　本明細書中の「置換されていてもよいＣ１－１０アルキル基」、「置換されていてもよいＣ２－１０アルケニル基」、「置換されていてもよいＣ２－１０アルキニル基」、「置換されていてもよいＣ３－１０シクロアルキル基」、「置換されていてもよいＣ３－１０シクロアルケニル基」、「置換されていてもよいＣ４－１０シクロアルカジエニル基」、「置換されていてもよいＣ６－１４アリール基」、「置換されていてもよいＣ７－１６アラルキル基」、「置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基」、「置換されていてもよい複素環基」、「置換されていてもよい５ないし７員含窒素飽和複素環」、「置換されていてもよい芳香族複素環基」、「置換されていてもよい縮合環基」、「置換されていてもよいベンゾフリル」および「置換されていてもよいインダニル」の置換基としては、以下の置換基Ａが挙げられる。 In the present specification, “optionally substituted C 1-10 alkyl group”, “optionally substituted C 2-10 alkenyl group”, “ optionally substituted C 2-10 alkynyl group”, “Optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “optionally substituted C 4-10 cycloalkadienyl group”, “Optionally substituted C 6-14 aryl group”, “ optionally substituted C 7-16 aralkyl group”, “ optionally substituted C 6-10 aryl-C 2-6 alkenyl group” , “Optionally substituted heterocyclic group”, “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring”, “optionally substituted aromatic heterocyclic group”, “substituted” `` May be a fused ring group '' or `` may be substituted Examples of the substituent of “benzofuryl” and “optionally substituted indanyl” include the following substituent A.

［置換基Ａ］
Ｃ１－６アルキル基、Ｃ２－６アルケニル基、Ｃ２－６アルキニル基、Ｃ３－８シクロアルキル基、Ｃ３－８シクロアルケニル基、Ｃ４－８シクロアルカジエニル基、Ｃ６－１４アリール基、Ｃ７－１６アラルキル基、Ｃ６－１０アリール－Ｃ２－６アルケニル基、複素環基；
ヒドロキシ基、Ｃ１－６アルコキシ基、Ｃ２－６アルケニルオキシ基、Ｃ２－６アルキニルオキシ基、Ｃ３－８シクロアルキルオキシ基、Ｃ３－８シクロアルケニルオキシ基、Ｃ４－８シクロアルカジエニルオキシ基、Ｃ６－１４アリールオキシ基、Ｃ７－１６アラルキルオキシ基、複素環オキシ基；
ホルミル基、Ｃ１－６アルキル－カルボニル基、Ｃ２－６アルケニル－カルボニル基、Ｃ２－６アルキニル－カルボニル基、Ｃ３－８シクロアルキル－カルボニル基、Ｃ３－８シクロアルケニル－カルボニル基、Ｃ４－８シクロアルカジエニル－カルボニル基、Ｃ６－１４アリール－カルボニル基、Ｃ７－１６アラルキル－カルボニル基、複素環カルボニル基；
カルボキシ基、Ｃ１－６アルコキシ－カルボニル基、Ｃ２－６アルケニルオキシ－カルボニル基、Ｃ２－６アルキニルオキシ－カルボニル基、Ｃ３－８シクロアルキルオキシ－カルボニル基、Ｃ３－８シクロアルケニルオキシ－カルボニル基、Ｃ４－８シクロアルカジエニルオキシ－カルボニル基、Ｃ６－１４アリールオキシ－カルボニル基、Ｃ７－１６アラルキルオキシ－カルボニル基、複素環オキシカルボニル基；
Ｃ１－６アルキル－カルボニルオキシ基、Ｃ２－６アルケニル－カルボニルオキシ基、Ｃ２－６アルキニル－カルボニルオキシ基、Ｃ３－８シクロアルキル－カルボニルオキシ基、Ｃ３－８シクロアルケニル－カルボニルオキシ基、Ｃ４－８シクロアルカジエニル－カルボニルオキシ基、Ｃ６－１４アリール－カルボニルオキシ基、Ｃ７－１６アラルキル－カルボニルオキシ基、複素環カルボニルオキシ基；
スルファニル基、Ｃ１－６アルキルスルファニル基、Ｃ２－６アルケニルスルファニル基、Ｃ２－６アルキニルスルファニル基、Ｃ３－８シクロアルキルスルファニル基、Ｃ３－８シクロアルケニルスルファニル基、Ｃ４－８シクロアルカジエニルスルファニル基、Ｃ６－１４アリールスルファニル基、Ｃ７－１６アラルキルスルファニル基、複素環スルファニル基；
スルフィニル基、Ｃ１－６アルキルスルフィニル基、Ｃ２－６アルケニルスルフィニル基、Ｃ２－６アルキニルスルフィニル基、Ｃ３－８シクロアルキルスルフィニル基、Ｃ３－８シクロアルケニルスルフィニル基、Ｃ４－８シクロアルカジエニルスルフィニル基、Ｃ６－１４アリールスルフィニル基、Ｃ７－１６アラルキルスルフィニル基、複素環スルフィニル基；
スルホニル基（スルホ基）、Ｃ１－６アルキルスルホニル基、Ｃ２－６アルケニルスルホニル基、Ｃ２－６アルキニルスルホニル基、Ｃ３－８シクロアルキルスルホニル基、Ｃ３－８シクロアルケニルスルホニル基、Ｃ４－８シクロアルカジエニルスルホニル基、Ｃ６－１４アリールスルホニル基、Ｃ７－１６アラルキルスルホニル基、複素環スルホニル基；
Ｃ１－６アルキルスルホニルオキシ基、Ｃ２－６アルケニルスルホニルオキシ基、Ｃ２－６アルキニルスルホニルオキシ基、Ｃ３－８シクロアルキルスルホニルオキシ基、Ｃ３－８シクロアルケニルスルホニルオキシ基、Ｃ４－８シクロアルカジエニルスルホニルオキシ基、Ｃ６－１４アリールスルホニルオキシ基、Ｃ７－１６アラルキルスルホニルオキシ基、複素環スルホニルオキシ基；
アミノ基、モノまたはジ－Ｃ１－６アルキルアミノ基、モノまたはジ－Ｃ２－６アルケニルアミノ基、モノまたはジ－Ｃ２－６アルキニルアミノ基、モノまたはジ－Ｃ３－８シクロアルキルアミノ基、モノまたはジ－Ｃ３－８シクロアルケニルアミノ基、モノまたはジ－Ｃ４－８シクロアルカジエニルアミノ基、モノまたはジ－Ｃ６－１４アリールアミノ基、モノまたはジ－Ｃ７－１６アラルキルアミノ基、モノまたはジ－複素環アミノ基；
カルバモイル基、モノまたはジ－Ｃ１－６アルキルカルバモイル基、モノまたはジ－Ｃ２－６アルケニルカルバモイル基、モノまたはジ－Ｃ２－６アルキニルカルバモイル基、モノまたはジ－Ｃ３－８シクロアルキルカルバモイル基、モノまたはジ－Ｃ３－８シクロアルケニルカルバモイル基、モノまたはジ－Ｃ４－８シクロアルカジエニルカルバモイル基、モノまたはジ－Ｃ６－１４アリールカルバモイル基、モノまたはジ－Ｃ７－１６アラルキルカルバモイル基、モノまたはジ－複素環カルバモイル基；
チオカルバモイル基、モノまたはジ－Ｃ１－６アルキルチオカルバモイル基、モノまたはジ－Ｃ２－６アルケニルチオカルバモイル基、モノまたはジ－Ｃ２－６アルキニルチオカルバモイル基、モノまたはジ－Ｃ３－８シクロアルキルチオカルバモイル基、モノまたはジ－Ｃ３－８シクロアルケニルチオカルバモイル基、モノまたはジ－Ｃ４－８シクロアルカジエニルチオカルバモイル基、モノまたはジ－Ｃ６－１４アリールチオカルバモイル基、モノまたはジ－Ｃ７－１６アラルキルチオカルバモイル基、モノまたはジ－複素環チオカルバモイル基；
ハロゲン原子；
シアノ基；
ニトロ基；
オキソ基；
チオキソ基；
等が挙げられる。置換基の数は、置換可能な数であれば特に限定されないが、好ましくは１乃至５個、より好ましくは１乃至３個である。複数の置換基が存在する場合、各置換基は、同一でも異なっていてもよい。当該置換基は、置換基Ａでさらに置換されていてもよい。 [Substituent A]
C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 3-8 cycloalkyl group, C 3-8 cycloalkenyl group, C 4-8 cycloalkadienyl group, C 6- A 14 aryl group, a C 7-16 aralkyl group, a C 6-10 aryl-C 2-6 alkenyl group, a heterocyclic group;
Hydroxy group, C 1-6 alkoxy group, C 2-6 alkenyloxy group, C 2-6 alkynyloxy group, C 3-8 cycloalkyloxy group, C 3-8 cycloalkenyloxy group, C 4-8 cycloalkaline Dienyloxy group, C 6-14 aryloxy group, C 7-16 aralkyloxy group, heterocyclic oxy group;
Formyl group, C 1-6 alkyl-carbonyl group, C 2-6 alkenyl-carbonyl group, C 2-6 alkynyl-carbonyl group, C 3-8 cycloalkyl-carbonyl group, C 3-8 cycloalkenyl-carbonyl group, A C 4-8 cycloalkadienyl-carbonyl group, a C 6-14 aryl-carbonyl group, a C 7-16 aralkyl-carbonyl group, a heterocyclic carbonyl group;
Carboxy group, C 1-6 alkoxy-carbonyl group, C 2-6 alkenyloxy-carbonyl group, C 2-6 alkynyloxy-carbonyl group, C 3-8 cycloalkyloxy-carbonyl group, C 3-8 cycloalkenyloxy -Carbonyl group, C 4-8 cycloalkadienyloxy-carbonyl group, C 6-14 aryloxy-carbonyl group, C 7-16 aralkyloxy-carbonyl group, heterocyclic oxycarbonyl group;
C 1-6 alkyl-carbonyloxy group, C 2-6 alkenyl-carbonyloxy group, C 2-6 alkynyl-carbonyloxy group, C 3-8 cycloalkyl-carbonyloxy group, C 3-8 cycloalkenyl-carbonyloxy group A group, a C 4-8 cycloalkadienyl-carbonyloxy group, a C 6-14 aryl-carbonyloxy group, a C 7-16 aralkyl-carbonyloxy group, a heterocyclic carbonyloxy group;
Sulfanyl group, C 1-6 alkylsulfanyl group, C 2-6 alkenylsulfanyl group, C 2-6 alkynylsulfanyl group, C 3-8 cycloalkylsulfanyl group, C 3-8 cycloalkenylsulfanyl group, C 4-8 cyclo Alkadienylsulfanyl group, C 6-14 arylsulfanyl group, C 7-16 aralkylsulfanyl group, heterocyclic sulfanyl group;
Sulfinyl group, C 1-6 alkylsulfinyl group, C 2-6 alkenylsulfinyl group, C 2-6 alkynylsulfinyl group, C 3-8 cycloalkylsulfinyl group, C 3-8 cycloalkenylsulfinyl group, C 4-8 cyclo An alkadienylsulfinyl group, a C 6-14 arylsulfinyl group, a C 7-16 aralkylsulfinyl group, a heterocyclic sulfinyl group;
Sulfonyl group (sulfo group), C 1-6 alkylsulfonyl group, C 2-6 alkenylsulfonyl group, C 2-6 alkynylsulfonyl group, C 3-8 cycloalkylsulfonyl group, C 3-8 cycloalkenylsulfonyl group, C 4-8 cycloalkadienylsulfonyl group, C 6-14 arylsulfonyl group, C 7-16 aralkylsulfonyl group, heterocyclic sulfonyl group;
C 1-6 alkylsulfonyloxy group, C 2-6 alkenylsulfonyloxy group, C 2-6 alkynylsulfonyloxy group, C 3-8 cycloalkylsulfonyloxy group, C 3-8 cycloalkenylsulfonyloxy group, C 4- 8 cycloalkadienylsulfonyloxy group, C 6-14 arylsulfonyloxy group, C 7-16 aralkylsulfonyloxy group, heterocyclic sulfonyloxy group;
Amino group, mono or di-C 1-6 alkylamino group, mono or di-C 2-6 alkenylamino group, mono or di-C 2-6 alkynylamino group, mono or di-C 3-8 cycloalkylamino Group, mono- or di-C 3-8 cycloalkenylamino group, mono- or di-C 4-8 cycloalkadienylamino group, mono- or di-C 6-14 arylamino group, mono- or di-C 7-16 An aralkylamino group, a mono- or di-heterocyclic amino group;
Carbamoyl group, mono or di-C 1-6 alkylcarbamoyl group, mono or di-C 2-6 alkenylcarbamoyl group, mono or di-C 2-6 alkynylcarbamoyl group, mono or di-C 3-8 cycloalkylcarbamoyl Group, mono or di-C 3-8 cycloalkenylcarbamoyl group, mono or di-C 4-8 cycloalkadienylcarbamoyl group, mono or di-C 6-14 arylcarbamoyl group, mono or di-C 7-16 An aralkylcarbamoyl group, a mono- or di-heterocyclic carbamoyl group;
Thiocarbamoyl group, mono or di-C 1-6 alkylthiocarbamoyl group, mono or di-C 2-6 alkenylthiocarbamoyl group, mono or di-C 2-6 alkynylthiocarbamoyl group, mono or di-C 3-8 A cycloalkylthiocarbamoyl group, a mono or di-C 3-8 cycloalkenylthiocarbamoyl group, a mono or di-C 4-8 cycloalkadienylthiocarbamoyl group, a mono or di-C 6-14 arylthiocarbamoyl group, a mono or Di-C 7-16 aralkylthiocarbamoyl group, mono- or di-heterocyclic thiocarbamoyl group;
A halogen atom;
A cyano group;
A nitro group;
An oxo group;
A thioxo group;
Etc. The number of substituents is not particularly limited as long as it can be substituted, but is preferably 1 to 5, more preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different. The substituent may be further substituted with the substituent A.

　本明細書中の「置換されていてもよいヒドロキシ基」としては、例えば、「置換されていてもよいＣ１－１０アルキル基」、「置換されていてもよいＣ２－１０アルケニル基」、「置換されていてもよいＣ３－１０シクロアルキル基」、「置換されていてもよいＣ３－１０シクロアルケニル基」、「置換されていてもよいＣ６－１４アリール基」、「置換されていてもよいＣ７－１６アラルキル基」、「置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基」、「置換されていてもよい複素環基」等から選ばれる置換基で置換されていてもよいヒドロキシ基が挙げられる。 Examples of the “optionally substituted hydroxy group” in the present specification include “an optionally substituted C 1-10 alkyl group”, “an optionally substituted C 2-10 alkenyl group”, “Optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “ optionally substituted C 6-14 aryl group”, “substituted Substituents selected from “ optionally substituted C 7-16 aralkyl group”, “ optionally substituted C 6-10 aryl-C 2-6 alkenyl group”, “optionally substituted heterocyclic group”, etc. And a hydroxy group which may be substituted with.

　本明細書中の「置換されていてもよいスルファニル基」としては、例えば、「置換されていてもよいＣ１－１０アルキル基」、「置換されていてもよいＣ２－１０アルケニル基」、「置換されていてもよいＣ３－１０シクロアルキル基」、「置換されていてもよいＣ３－１０シクロアルケニル基」、「置換されていてもよいＣ６－１４アリール基」、「置換されていてもよいＣ７－１６アラルキル基」、「置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基」、「置換されていてもよい複素環基」等から選ばれる置換基で置換されていてもよいスルファニル基が挙げられる。 Examples of the “optionally substituted sulfanyl group” in the present specification include “an optionally substituted C 1-10 alkyl group”, “an optionally substituted C 2-10 alkenyl group”, “Optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “ optionally substituted C 6-14 aryl group”, “substituted Substituents selected from “ optionally substituted C 7-16 aralkyl group”, “ optionally substituted C 6-10 aryl-C 2-6 alkenyl group”, “optionally substituted heterocyclic group”, etc. And a sulfanyl group which may be substituted with.

　本明細書中の「置換されていてもよいアミノ基」としては、例えば、「置換されていてもよいＣ１－１０アルキル基」、「置換されていてもよいＣ２－１０アルケニル基」、「置換されていてもよいＣ３－１０シクロアルキル基」、「置換されていてもよいＣ３－１０シクロアルケニル基」、「置換されていてもよいＣ６－１４アリール基」、「置換されていてもよいＣ７－１６アラルキル基」、「置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基」、「置換されていてもよい複素環基」、「アシル基」等から選ばれる置換基でモノまたはジ置換されていてもよいアミノ基が挙げられる。 Examples of the “optionally substituted amino group” in the present specification include “an optionally substituted C 1-10 alkyl group”, “an optionally substituted C 2-10 alkenyl group”, “Optionally substituted C 3-10 cycloalkyl group”, “optionally substituted C 3-10 cycloalkenyl group”, “ optionally substituted C 6-14 aryl group”, “substituted Optionally substituted C 7-16 aralkyl group ”,“ optionally substituted C 6-10 aryl-C 2-6 alkenyl group ”,“ optionally substituted heterocyclic group ”,“ acyl group ”, etc. And an amino group which may be mono- or di-substituted with a substituent selected from:

　本明細書中の「アシル基」としては、例えば、式：－ＣＯＲＡ、－ＣＯ－ＯＲＡ、－Ｓ（Ｏ）２ＲＡ、－ＳＯＲＡ、－ＣＯ－ＮＲＡ’ＲＢ’、－ＣＳ－ＮＲＡ’ＲＢ’、－Ｓ（Ｏ）２ＮＲＡ’ＲＢ’［式中、ＲＡは、水素原子、置換されていてもよい炭化水素基、または置換されていてもよい複素環基を示す。ＲＡ’およびＲＢ’は、同一または異なって、水素原子、置換されていてもよい炭化水素基、または置換されていてもよい複素環基を示すか、ＲＡ’およびＲＢ’は、隣接する窒素原子とともに、置換されていてもよい含窒素複素環を形成していてもよい］で表される基等が挙げられる。 As the "acyl group" in the present specification, for example, the formula: -COR A, -CO-OR A , -S (O) 2 R A, -SOR A, -CO-NR A 'R B', - CS-NR A 'R B ', -S (O) 2 NR A 'R B ' [wherein, R A represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted complex. A ring group is shown. R A ′ and R B ′ are the same or different and each represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group, or R A ′ and R B ′ are A nitrogen-containing heterocyclic ring which may be substituted with an adjacent nitrogen atom may be formed], and the like.

　ＲＡ’およびＲＢ’が隣接する窒素原子とともに形成する「置換されていてもよい含窒素複素環」における「含窒素複素環」としては、例えば、環構成原子として炭素原子以外に少なくとも１個の窒素原子を含み、さらに酸素原子、硫黄原子および窒素原子から選ばれるヘテロ原子を１ないし２個含有していてもよい５ないし７員の含窒素複素環が挙げられる。該含窒素複素環の好適な例としては、ピロリジン、イミダゾリジン、ピラゾリジン、ピペリジン、ピペラジン、アゼパン、モルホリン、チオモルホリン等が挙げられる。 The “nitrogen-containing heterocycle” in the “optionally substituted nitrogen-containing heterocycle” formed by R A ′ and R B ′ together with the adjacent nitrogen atom includes, for example, at least one ring-constituting atom other than a carbon atom And a 5- to 7-membered nitrogen-containing heterocyclic ring which may contain 1 to 2 heteroatoms selected from oxygen, sulfur and nitrogen atoms. Preferable examples of the nitrogen-containing heterocycle include pyrrolidine, imidazolidine, pyrazolidine, piperidine, piperazine, azepane, morpholine, thiomorpholine and the like.

　該含窒素複素環は、置換可能な位置に１ないし５個（好ましくは１または２個）の置換基を有していてもよい。このような置換基としては、前記の置換基Ａが挙げられる。置換基が２個以上である場合、各置換基は同一でも異なっていてもよい。 The nitrogen-containing heterocycle may have 1 to 5 (preferably 1 or 2) substituents at substitutable positions. Examples of such a substituent include the above-described substituent A. When there are two or more substituents, each substituent may be the same or different.

　以下、式（Ｉ）について説明する。 Hereinafter, the formula (I) will be described.

　式（Ｉ）中、式； In formula (I), formula;

Figure JPOXMLDOC01-appb-C000017
Figure JPOXMLDOC01-appb-C000017

で表される部分構造は、式； The partial structure represented by the formula:

Figure JPOXMLDOC01-appb-C000018
Figure JPOXMLDOC01-appb-C000018

で表される構造が好ましい。 The structure represented by these is preferable.

　環Ａは、置換されていてもよい５ないし７員含窒素飽和複素環を示す。
　環Ａで示される「置換されていてもよい５ないし７員含窒素飽和複素環」の「５ないし７員含窒素飽和複素環」は、好ましくは、ピロリジン環、ピペリジン環またはアゼパン環であり、特に好ましくは、ピペリジン環である。
　環Ａは、
好ましくは、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり、
特に好ましくは、ピペリジン環である。 Ring A represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring which may be substituted.
The “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring A is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
Ring A is
Preferably, each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted,
More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl),
More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is a piperidine ring.

　Ｒ１は、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよい芳香族複素環基を示す。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、置換されていてもよいＣ６－１４アリール基を示す。）で表される基；
(3) －（ＣＨ２）ｎ－Ｒｚ（式中、Ｒｚは、置換されていてもよいＣ６－１４アリール基を示し、ｎは、１ないし５の整数を示す。）で表される基；
(4) 置換されていてもよいＣ６－１４アリール基；または
(5) 置換されていてもよい縮合環基
を示す。 R 1 is
(1) —CH═CH—R x (wherein R x represents an optionally substituted C 6-14 aryl group or an optionally substituted aromatic heterocyclic group). Group;
(2) (wherein, R y represents an optionally substituted C 6-14 aryl group.) -CH 2 -O-R y group represented by;
(3) - (CH 2) n -R z ( wherein, R z is substituted indicates which may C 6-14 aryl group, n is 1 to an integer of 5.) Is represented by Group;
(4) an optionally substituted C 6-14 aryl group; or
(5) An optionally substituted condensed ring group.

　Ｒ１は、好ましくは、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、または置換されていてもよい５または６員の単環式芳香族複素環基（好ましくはピリジル）である。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である。）で表される基；
(3) －（ＣＨ２）ｎ－Ｒｚ（式中、Ｒｚは、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり、ｎは、１ないし５の整数である。）で表される基；
(4) 置換されていてもよいＣ６－１０アリール基（好ましくはフェニル、ナフチル）；
(5) 置換されていてもよい８ないし１２員の縮合芳香族複素環基（好ましくはベンゾフリル）；または
(6) 置換されていてもよい８ないし１２員の縮合非芳香族炭化水素基（好ましくはインダニル）
であり、
より好ましくは、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、ニトロ基でそれぞれ置換されていてもよい、Ｃ６－１０アリール基（好ましくはフェニル）または５または６員の単環式芳香族複素環基（好ましくはピリジル）である。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である。）で表される基； 
(3) －（ＣＨ２）ｎ－Ｒｚ（式中、Ｒｚは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり、ｎは、１ないし５の整数（好ましくは３）である。）で表される基；
(4) ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル、ナフチル）；
(5) ８ないし１２員の縮合芳香族複素環基（好ましくはベンゾフリル）；または
(6) ８ないし１２員の縮合非芳香族炭化水素基（好ましくはインダニル）であり、
さらに好ましくは、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、または５または６員の単環式芳香族複素環基（好ましくはピリジル）である。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である。）で表される基；
(3) －（ＣＨ２）ｎ－Ｒｚ（式中、Ｒｚは、Ｃ６－１０アリール基（好ましくはフェニル）であり、ｎは、１ないし３の整数（好ましくは３）である。）で表される基；
(4) ニトロ基とＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）；
(5) ベンゾフリル；または
(6) インダニル
であり、
特に好ましくは、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である。）で表される基；
(3) －（ＣＨ２）ｎ－Ｒｚ（式中、Ｒｚは、Ｃ６－１０アリール基（好ましくはフェニル）であり、ｎは、１ないし３の整数（好ましくは３）である。）で表される基；
(4) １個のニトロ基と１または２個のＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）；または
(5) インダニル
である。 R 1 is preferably
(1) —CH═CH—R x (wherein R x is an optionally substituted C 6-10 aryl group (preferably phenyl), or an optionally substituted 5- or 6-membered monocycle) A group represented by the formula aromatic heterocyclic group (preferably pyridyl);
(2) a group represented by —CH 2 —O—R y (wherein R y is an optionally substituted C 6-10 aryl group (preferably phenyl));
(3) — (CH 2 ) n —R z (wherein R z is an optionally substituted C 6-10 aryl group (preferably phenyl), and n is an integer of 1 to 5) A group represented by:
(4) an optionally substituted C 6-10 aryl group (preferably phenyl, naphthyl);
(5) an optionally substituted 8- to 12-membered fused aromatic heterocyclic group (preferably benzofuryl); or
(6) An optionally substituted 8- to 12-membered condensed non-aromatic hydrocarbon group (preferably indanyl)
And
More preferably,
(1) —CH═CH—R x , wherein R x is a C 6-10 aryl group (preferably phenyl), each optionally substituted with a nitro group, or a 5- or 6-membered monocyclic aromatic Group heterocyclic group (preferably pyridyl));
(2) a group represented by —CH 2 —O—R y (wherein R y is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group);
(3) — (CH 2 ) n —R z , wherein R z is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group, and n is 1 to 5 A group represented by an integer (preferably 3);
(4) a C 6-10 aryl group (preferably phenyl, naphthyl) optionally substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
(5) 8- to 12-membered fused aromatic heterocyclic group (preferably benzofuryl); or
(6) an 8- to 12-membered condensed non-aromatic hydrocarbon group (preferably indanyl),
More preferably,
(1) —CH═CH—R x (wherein R x is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group), or a 5- or 6-membered monocyclic aromatic group A group represented by a heterocyclic group (preferably pyridyl);
(2) a group represented by —CH 2 —O—R y (wherein R y is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group);
(3) — (CH 2 ) n —R z (wherein R z is a C 6-10 aryl group (preferably phenyl), and n is an integer of 1 to 3 (preferably 3). A group represented by
(4) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
(5) benzofuryl; or
(6) Indanyl,
Particularly preferably,
(1) a group represented by —CH═CH—R x (wherein R x is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group);
(2) a group represented by —CH 2 —O—R y (wherein R y is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group);
(3) — (CH 2 ) n —R z (wherein R z is a C 6-10 aryl group (preferably phenyl), and n is an integer of 1 to 3 (preferably 3). A group represented by
(4) a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two C 1-6 alkoxy groups (preferably methoxy, ethoxy); or
(5) Indanyl.

　Ｒ２、Ｒ３、Ｒ４およびＲ５は、それぞれ独立して、水素原子または置換基を示す。
　好ましくは、Ｒ２、Ｒ３、Ｒ４およびＲ５は、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　別の実施態様として、好ましくは、Ｒ２、Ｒ３、Ｒ４およびＲ５の少なくとも１つが置換基であり、かつ残りが、それぞれ独立して、水素原子または置換基である。
　より好ましくは、Ｒ２、Ｒ３、Ｒ４およびＲ５の少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　さらに好ましくは、Ｒ２、Ｒ３、Ｒ４およびＲ５の少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）である。
　さらにより好ましくは、Ｒ２、Ｒ３、Ｒ４およびＲ５の１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。
　特に好ましくは、Ｒ２、Ｒ３、Ｒ４およびＲ５のうち、Ｒ３またはＲ４がＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。 R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom or a substituent.
Preferably, R 2 , R 3 , R 4 and R 5 are each independently a hydrogen atom or an optionally substituted C 1-6 alkyl group (preferably methyl).
In another embodiment, preferably, at least one of R 2 , R 3 , R 4 and R 5 is a substituent, and the rest are each independently a hydrogen atom or a substituent.
More preferably, at least one of R 2 , R 3 , R 4 and R 5 is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom. Alternatively, it is an optionally substituted C 1-6 alkyl group (preferably methyl).
More preferably, at least one of R 2 , R 3 , R 4 and R 5 is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
Even more preferably, one of R 2 , R 3 , R 4 and R 5 is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms.
Particularly preferably, among R 2 , R 3 , R 4 and R 5 , R 3 or R 4 is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.

　Ｒ６は、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基を示す。
　Ｒ６は、
好ましくは、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、Ｃ６－１４アリール基（好ましくはフェニル）、Ｃ７－１６アラルキル基（好ましくはベンジル）またはＣ６－１０アリール－Ｃ２－６アルケニル基（好ましくは３－フェニル－２－プロペニル）であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ７－１６アラルキル基（好ましくはベンジル）、またはＣ６－１０アリール－Ｃ２－６アルケニル基（好ましくは３－フェニル－２－プロペニル）であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり、
特に好ましくは、１個のＣ１－６アルキル基（好ましくはメチル）でメタ位が置換されたフェニルである。 R 6 is optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show.
R 6 is
Preferably, a C 6-14 aryl group (preferably phenyl), a C 7-16 aralkyl group (preferably benzyl) or C 6-, each optionally substituted with a C 1-6 alkyl group (preferably methyl). 10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl);
More preferably, C 1-6 alkyl group (preferably methyl) optionally C 6-10 aryl group optionally substituted by (preferably phenyl), C 1-6 alkyl group (preferably methyl) substituted with Or a C 7-16 aralkyl group (preferably benzyl) or a C 6-10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl);
More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).

　以下、式（Ｉａ）について説明する。
　環Ａａは、置換されていてもよい５ないし７員含窒素飽和複素環を示す。
　環Ａａで示される「置換されていてもよい５ないし７員含窒素飽和複素環」の「５ないし７員含窒素飽和複素環」は、好ましくは、ピロリジン環、ピペリジン環またはアゼパン環であり、特に好ましくは、ピペリジン環である。
　環Ａａは、
好ましくは、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり、
特に好ましくは、ピペリジン環である。 Hereinafter, Formula (Ia) will be described.
Ring Aa represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring.
The “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring Aa is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
Ring Aa is
Preferably, each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted,
More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl),
More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is a piperidine ring.

　Ｒ１ａは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよい芳香族複素環基を示す。
　Ｒ１ａは、
好ましくは、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、または置換されていてもよい５または６員の単環式芳香族複素環基（好ましくはピリジル）であり、
より好ましくは、ニトロ基でそれぞれ置換されていてもよい、Ｃ６－１０アリール基（好ましくはフェニル）または５または６員の単環式芳香族複素環基（好ましくはピリジル）であり、
さらに好ましくは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、または５または６員の単環式芳香族複素環基（好ましくはピリジル）であり、
特に好ましくは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である。 R 1a represents an optionally substituted C 6-14 aryl group or an optionally substituted aromatic heterocyclic group.
R 1a is
Preferably, it is an optionally substituted C 6-10 aryl group (preferably phenyl), or an optionally substituted 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl).
More preferably, a C 6-10 aryl group (preferably phenyl) or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl), each of which may be substituted with a nitro group,
More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group, or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl),
Particularly preferred is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group.

　Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つは置換基を示し、かつ残りは、それぞれ独立して、水素原子または置換基を示す。
　好ましくは、Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　より好ましくは、Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）である。
　さらに好ましくは、Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。
　特に好ましくは、Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａのうち、Ｒ３ａまたはＲ４ａがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。 At least one of R 2a , R 3a , R 4a and R 5a represents a substituent, and the rest each independently represents a hydrogen atom or a substituent.
Preferably, at least one of R 2a , R 3a , R 4a and R 5a is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or An optionally substituted C 1-6 alkyl group (preferably methyl).
More preferably, at least one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
More preferably, one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
Particularly preferably, among R 2a , R 3a , R 4a and R 5a , R 3a or R 4a is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.

　Ｒ６ａは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよいＣ７－１６アラルキル基を示す。
　Ｒ６ａは、
好ましくは、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、Ｃ６－１４アリール基（好ましくはフェニル）またはＣ７－１６アラルキル基（好ましくはベンジル）であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、またはＣ７－１３アラルキル基（好ましくはベンジル）であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり、
特に好ましくは、１個のＣ１－６アルキル基（好ましくはメチル）でメタ位が置換されたフェニルである。 R 6a represents an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group.
R 6a is
Preferably, it is a C 6-14 aryl group (preferably phenyl) or a C 7-16 aralkyl group (preferably benzyl), each optionally substituted with a C 1-6 alkyl group (preferably methyl).
More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl), or a C 7-13 aralkyl group (preferably benzyl).
More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).

　なお、式（Ｉａ）において、Ｒ１ａの結合は、カルボニルに対して、（Ｅ）および（Ｚ）のいずれでもよいが、好ましくは（Ｅ）である。 In formula (Ia), the bond of R 1a may be any of (E) and (Z) with respect to carbonyl, but is preferably (E).

　以下、式（Ｉｂ）について説明する。
　環Ａｂは、置換されていてもよい５ないし７員含窒素飽和複素環を示す。
　環Ａｂで示される「置換されていてもよい５ないし７員含窒素飽和複素環」の「５ないし７員含窒素飽和複素環」は、好ましくは、ピロリジン環、ピペリジン環またはアゼパン環であり、特に好ましくは、ピペリジン環である。
　環Ａｂは、
好ましくは、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり、
特に好ましくは、ピペリジン環である。 Hereinafter, the formula (Ib) will be described.
Ring Ab represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring which may be substituted.
The “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring Ab is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
Ring Ab is
Preferably, each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted,
More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl),
More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is a piperidine ring.

　Ｒ１ｂは、
(1) ニトロ基およびＣ１－６アルコキシ基で置換されたＣ６－１４アリール基、
(2) 置換されていてもよいベンゾフリル、または
(3) 置換されていてもよいインダニル
を示す。
　Ｒ１ｂは、
好ましくは、
(1) ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）、
(2) 置換されていてもよいベンゾフリル、または
(3) 置換されていてもよいインダニル
であり、
より好ましくは、
(1) ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）、
(2) ベンゾフリル、または
(3) インダニル
であり、
さらに好ましくは、
(1) １個のニトロ基と１または２個（好ましくは１個）のＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）、
(2) ベンゾフリル、または
(3) インダニル
であり、
特に好ましくは、
(1) １個のニトロ基と１または２個（好ましくは１個）のＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）、または
(2) インダニル
である。 R 1b is
(1) a C 6-14 aryl group substituted with a nitro group and a C 1-6 alkoxy group,
(2) optionally substituted benzofuryl, or
(3) Indanyl which may be substituted.
R 1b is
Preferably,
(1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy),
(2) optionally substituted benzofuryl, or
(3) optionally substituted indanyl,
More preferably,
(1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy),
(2) benzofuryl, or
(3) Indanyl,
More preferably,
(1) a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two (preferably one) C 1-6 alkoxy groups (preferably methoxy, ethoxy),
(2) benzofuryl, or
(3) Indanyl,
Particularly preferably,
(1) a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two (preferably one) C 1-6 alkoxy groups (preferably methoxy, ethoxy), or
(2) Indanyl.

　Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂは、それぞれ独立して、水素原子または置換基を示す。
　好ましくは、Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂは、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　別の実施態様として、好ましくは、Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つが置換基であり、かつ残りが、それぞれ独立して、水素原子または置換基である。
　より好ましくは、Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　さらに好ましくは、Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）である。
　さらにより好ましくは、Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。
　特に好ましくは、Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂのうち、Ｒ３ｂまたはＲ４ｂがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。 R 2b , R 3b , R 4b and R 5b each independently represent a hydrogen atom or a substituent.
Preferably, R 2b , R 3b , R 4b and R 5b are each independently a hydrogen atom or an optionally substituted C 1-6 alkyl group (preferably methyl).
In another embodiment, preferably, at least one of R 2b , R 3b , R 4b and R 5b is a substituent, and the rest are each independently a hydrogen atom or a substituent.
More preferably, at least one of R 2b , R 3b , R 4b and R 5b is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom. Alternatively, it is an optionally substituted C 1-6 alkyl group (preferably methyl).
More preferably, at least one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
Even more preferably, one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms.
Particularly preferably, among R 2b , R 3b , R 4b and R 5b , R 3b or R 4b is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.

　Ｒ６ｂは、置換されていてもよいＣ６－１４アリール基を示す。
　Ｒ６ｂは、
好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１４アリール基（好ましくはフェニル）であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり、
特に好ましくは、１個のＣ１－６アルキル基（好ましくはメチル）でメタ位が置換されたフェニルである。 R 6b represents an optionally substituted C 6-14 aryl group.
R 6b is
Preferably, it is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).

　以下、式（Ｉｃ）について説明する。
　環Ａｃは、５ないし７員含窒素飽和複素環を示す。
　環Ａｃは、好ましくは、ピロリジン環、ピペリジン環またはアゼパン環であり、より好ましくは、ピペリジン環である。 Hereinafter, the formula (Ic) will be described.
Ring Ac represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring.
Ring Ac is preferably a pyrrolidine ring, piperidine ring or azepane ring, more preferably a piperidine ring.

　Ｒ１ｃは、置換されていてもよいＣ６－１４アリール基を示す。
　Ｒ１ｃは、
好ましくは、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり、
より好ましくは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である。 R 1c represents an optionally substituted C 6-14 aryl group.
R 1c is
Preferably, it is an optionally substituted C 6-10 aryl group (preferably phenyl),
More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group.

　Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃは、それぞれ独立して、水素原子または置換基を示す。
　好ましくは、Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃは、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　別の実施態様として、好ましくは、Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの少なくとも１つが置換基であり、かつ残りが、それぞれ独立して、水素原子または置換基である。
　より好ましくは、Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　さらに好ましくは、Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）である。
　さらにより好ましくは、Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。
　特に好ましくは、Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃのうち、Ｒ３ｃまたはＲ４ｃがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。 R 2c , R 3c , R 4c and R 5c each independently represent a hydrogen atom or a substituent.
Preferably, R 2c , R 3c , R 4c and R 5c are each independently a hydrogen atom or an optionally substituted C 1-6 alkyl group (preferably methyl).
In another embodiment, preferably, at least one of R 2c , R 3c , R 4c and R 5c is a substituent, and the rest are each independently a hydrogen atom or a substituent.
More preferably, at least one of R 2c , R 3c , R 4c and R 5c is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom Alternatively, it is an optionally substituted C 1-6 alkyl group (preferably methyl).
More preferably, at least one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
Even more preferably, one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms.
Particularly preferably, among R 2c , R 3c , R 4c and R 5c , R 3c or R 4c is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.

　Ｒ６ｃは、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基を示す。
　Ｒ６ｃは、
好ましくは、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、Ｃ６－１４アリール基（好ましくはフェニル）、Ｃ７－１６アラルキル基（好ましくはベンジル）またはＣ６－１０アリール－Ｃ２－６アルケニル基（好ましくは３－フェニル－２－プロペニル）であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ７－１６アラルキル基（好ましくはベンジル）、またはＣ６－１０アリール－Ｃ２－６アルケニル基（好ましくは３－フェニル－２－プロペニル）であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり、
特に好ましくは、１個のＣ１－６アルキル基（好ましくはメチル）でメタ位が置換されたフェニルである。 R 6c is an optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show.
R 6c is
Preferably, a C 6-14 aryl group (preferably phenyl), a C 7-16 aralkyl group (preferably benzyl) or C 6-, each optionally substituted with a C 1-6 alkyl group (preferably methyl). 10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl);
More preferably, C 1-6 alkyl group (preferably methyl) optionally C 6-10 aryl group optionally substituted by (preferably phenyl), C 1-6 alkyl group (preferably methyl) substituted with Or a C 7-16 aralkyl group (preferably benzyl) or a C 6-10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl);
More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).

　以下、式（Ｉｄ）について説明する。
　環Ａｄは、置換されていてもよい５ないし７員含窒素飽和複素環を示す。
　環Ａｄで示される「置換されていてもよい５ないし７員含窒素飽和複素環」の「５ないし７員含窒素飽和複素環」は、好ましくは、ピロリジン環、ピペリジン環またはアゼパン環であり、特に好ましくは、ピペリジン環である。
　環Ａｄは、
好ましくは、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり、
特に好ましくは、ピペリジン環である。 Hereinafter, the formula (Id) will be described.
Ring Ad represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring.
The “5- to 7-membered nitrogen-containing saturated heterocycle” of the “optionally substituted 5- to 7-membered nitrogen-containing saturated heterocycle” represented by ring Ad is preferably a pyrrolidine ring, a piperidine ring or an azepane ring, Particularly preferred is a piperidine ring.
Ring Ad is
Preferably, each is a pyrrolidine ring, piperidine ring or azepane ring, each of which may be substituted,
More preferably, a pyrrolidine ring, a piperidine ring or an azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl),
More preferably, it is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is a piperidine ring.

　Ｒ１ｄは、置換されていてもよいＣ６－１４アリール基を示す。
　Ｒ１ｄは、
好ましくは、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり、
より好ましくは、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり、
特に好ましくは、Ｃ６－１０アリール基（好ましくはフェニル）である。 R 1d represents an optionally substituted C 6-14 aryl group.
R 1d is
Preferably, it is an optionally substituted C 6-10 aryl group (preferably phenyl),
More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group,
Particularly preferred is a C 6-10 aryl group (preferably phenyl).

　Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの少なくとも１つは置換基を示し、かつ残りは、それぞれ独立して、水素原子または置換基を示す。
　好ましくは、Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）である。
　より好ましくは、Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）である。
　さらに好ましくは、Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。
　特に好ましくは、Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄのうち、Ｒ３ｄまたはＲ４ｄがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子である。 At least one of R 2d , R 3d , R 4d and R 5d represents a substituent, and the rest each independently represents a hydrogen atom or a substituent.
Preferably, at least one of R 2d , R 3d , R 4d and R 5d is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or An optionally substituted C 1-6 alkyl group (preferably methyl).
More preferably, at least one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or C 1-6 alkyl A group (preferably methyl).
More preferably, one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.
Particularly preferably, among R 2d , R 3d , R 4d and R 5d , R 3d or R 4d is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms.

　Ｒ６ｄは、置換されていてもよいＣ６－１４アリール基を示す。
　Ｒ６ｄは、
好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１４アリール基（好ましくはフェニル）であり、
より好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり、
さらに好ましくは、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり、
特に好ましくは、１個のＣ１－６アルキル基（好ましくはメチル）でメタ位が置換されたフェニルである。 R 6d represents an optionally substituted C 6-14 aryl group.
R 6d is
Preferably, it is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
More preferably, it is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
More preferably, it is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl),
Particularly preferred is phenyl substituted at the meta position with one C 1-6 alkyl group (preferably methyl).

　ｎｄは、１ないし５の整数を示す。
　ｎｄは、好ましくは、１ないし３の整数であり、より好ましくは、３である。 n d represents an integer of 1 to 5.
n d is preferably an integer of 1 to 3, and more preferably 3.

　化合物（Ｉ）のうち、化合物（Ｉａ）、化合物（Ｉｂ）、化合物（Ｉｃ）および化合物（Ｉｄ）は新規化合物である。
　以下に、好適な化合物、化合物（Ｉａ）、化合物（Ｉｂ）、化合物（Ｉｃ）および化合物（Ｉｄ）を示す。 Of compound (I), compound (Ia), compound (Ib), compound (Ic) and compound (Id) are novel compounds.
In the following, preferred compounds, compound (Ia), compound (Ib), compound (Ic) and compound (Id) are shown.

［化合物Ａ１］
環Ａａが、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ａが、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ａが、置換されていてもよいＣ６－１４アリール基、または置換されていてもよいＣ７－１６アラルキル基である、
化合物（Ｉａ）。 [Compound A1]
Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
R 1a is an optionally substituted C 6-10 aryl group (preferably phenyl);
At least one of R 2a , R 3a , R 4a and R 5a is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted An optionally substituted C 1-6 alkyl group (preferably methyl); and R 6a is an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group. ,
Compound (Ia).

［化合物Ａ１’］
環Ａａが、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ａが、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、または置換されていてもよい５または６員の単環式芳香族複素環基（好ましくはピリジル）であり；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ａが、置換されていてもよいＣ６－１４アリール基、または置換されていてもよいＣ７－１６アラルキル基である、
化合物（Ｉａ）。 [Compound A1 ′]
Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
R 1a is an optionally substituted C 6-10 aryl group (preferably phenyl), or an optionally substituted 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl);
At least one of R 2a , R 3a , R 4a and R 5a is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted An optionally substituted C 1-6 alkyl group (preferably methyl); and R 6a is an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group. ,
Compound (Ia).

［化合物Ａ２］
環Ａａが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ａが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ａが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、Ｃ６－１４アリール基（好ましくはフェニル）またはＣ７－１６アラルキル基（好ましくはベンジル）である、
化合物（Ｉａ）。 [Compound A2]
Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
At least one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And a C 6-14 aryl group (preferably phenyl) or a C 7-16 aralkyl group (preferably R 6a ), each optionally substituted with a C 1-6 alkyl group (preferably methyl). Is benzyl),
Compound (Ia).

［化合物Ａ２’］
環Ａａが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ａが、ニトロ基でそれぞれ置換されていてもよい、Ｃ６－１０アリール基（好ましくはフェニル）または５または６員の単環式芳香族複素環基（好ましくはピリジル）であり；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ａが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、Ｃ６－１４アリール基（好ましくはフェニル）またはＣ７－１６アラルキル基（好ましくはベンジル）である、
化合物（Ｉａ）。 [Compound A2 ′]
Ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1a is a C 6-10 aryl group (preferably phenyl) or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl), each optionally substituted with a nitro group;
At least one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And a C 6-14 aryl group (preferably phenyl) or a C 7-16 aralkyl group (preferably R 6a ), each optionally substituted with a C 1-6 alkyl group (preferably methyl). Is benzyl),
Compound (Ia).

［化合物Ａ３］
環Ａａが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり；
Ｒ１ａが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ａが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、またはＣ７－１３アラルキル基（好ましくはベンジル）である、
化合物（Ｉａ）。 [Compound A3]
Ring Aa is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
One of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and R 6a is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), or a C 7-13 aralkyl group (preferably benzyl).
Compound (Ia).

［化合物Ａ３’］
環Ａａが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり；
Ｒ１ａが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、または５または６員の単環式芳香族複素環基（好ましくはピリジル）であり；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ａが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、またはＣ７－１３アラルキル基（好ましくはベンジル）である、
化合物（Ｉａ）。 [Compound A3 ′]
Ring Aa is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group, or a 5- or 6-membered monocyclic aromatic heterocyclic group (preferably pyridyl);
One of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and R 6a is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), or a C 7-13 aralkyl group (preferably benzyl).
Compound (Ia).

［化合物Ａ４］
環Ａａが、ピペリジン環であり；
Ｒ１ａが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａのうち、Ｒ３ａまたはＲ４ａがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ａが、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）である、
化合物（Ｉａ）。 [Compound A4]
Ring Aa is a piperidine ring;
R 1a is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
Of R 2a , R 3a , R 4a and R 5a , R 3a or R 4a is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms; and R 6a is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl),
Compound (Ia).

［化合物Ｂ１］
環Ａｂが、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｂが、ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１４アリール基（好ましくはフェニル）であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ｂが、置換されていてもよいＣ６－１４アリール基である、
化合物（Ｉｂ）。
［化合物Ｂ１’］
環Ａｂが、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｂが、
(1) ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）、
(2) 置換されていてもよいベンゾフリル、または
(3) 置換されていてもよいインダニル
であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ｂが、置換されていてもよいＣ６－１４アリール基である、
化合物（Ｉｂ）。 [Compound B1]
Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
R 1b is a C 6-14 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
At least one of R 2b , R 3b , R 4b and R 5b is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted An optionally substituted C 1-6 alkyl group (preferably methyl); and R 6b is an optionally substituted C 6-14 aryl group,
Compound (Ib).
[Compound B1 ′]
Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
R 1b is
(1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy),
(2) optionally substituted benzofuryl, or
(3) optionally substituted indanyl;
At least one of R 2b , R 3b , R 4b and R 5b is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted An optionally substituted C 1-6 alkyl group (preferably methyl); and R 6b is an optionally substituted C 6-14 aryl group,
Compound (Ib).

［化合物Ｂ２］
環Ａｂが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｂが、ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１４アリール基（好ましくはフェニル）である、
化合物（Ｉｂ）。 [Compound B2]
Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1b is a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
At least one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And R 6b is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
Compound (Ib).

［化合物Ｂ２’］
環Ａｂが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｂが、
(1) ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）、
(2) 置換されていてもよいベンゾフリル、または
(3) 置換されていてもよいインダニル
であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１４アリール基（好ましくはフェニル）である、
化合物（Ｉｂ）。 [Compound B2 ′]
Ring Ab is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1b is
(1) a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy),
(2) optionally substituted benzofuryl, or
(3) optionally substituted indanyl;
At least one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And R 6b is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl).
Compound (Ib).

［化合物Ｂ３］
環Ａｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり；
Ｒ１ｂが、ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である、
化合物（Ｉｂ）。 [Compound B3]
Ring Ab is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1b is a C 6-10 aryl group (preferably phenyl) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy);
One of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and R 6b is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl),
Compound (Ib).

［化合物Ｂ３’］
環Ａｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり；
Ｒ１ｂが、
(1) ニトロ基およびＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）（好ましくは１個のニトロ基と１または２個（好ましくは１個）のＣ１－６アルコキシ基）で置換されたＣ６－１０アリール基（好ましくはフェニル）、
(2) ベンゾフリル、または
(3) インダニル
であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）である、
化合物（Ｉｂ）。 [Compound B3 ′]
Ring Ab is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1b is
(1) substituted with a nitro group and a C 1-6 alkoxy group (preferably methoxy, ethoxy) (preferably one nitro group and one or two (preferably one) C 1-6 alkoxy groups) A C 6-10 aryl group (preferably phenyl),
(2) benzofuryl, or
(3) indanyl;
One of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and R 6b is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl),
Compound (Ib).

［化合物Ｂ４］
環Ａｂが、ピペリジン環であり；
Ｒ１ｂが、１個のニトロ基と１または２個（好ましくは１個）のＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂのうち、Ｒ３ｂまたはＲ４ｂがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）である、
化合物（Ｉｂ）。 [Compound B4]
Ring Ab is a piperidine ring;
R 1b is a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two (preferably one) C 1-6 alkoxy groups (preferably methoxy, ethoxy). Yes;
Of R 2b , R 3b , R 4b and R 5b , R 3b or R 4b is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms; and R 6b is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl),
Compound (Ib).

［化合物Ｂ４’］
環Ａｂが、ピペリジン環であり；
Ｒ１ｂが、
(1) １個のニトロ基と１または２個（好ましくは１個）のＣ１－６アルコキシ基（好ましくはメトキシ、エトキシ）で置換されたＣ６－１０アリール基（好ましくはフェニル）、または
(2) インダニル
であり；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂのうち、Ｒ３ｂまたはＲ４ｂがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ｂが、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）である、
化合物（Ｉｂ）。 [Compound B4 ′]
Ring Ab is a piperidine ring;
R 1b is
(1) a C 6-10 aryl group (preferably phenyl) substituted with one nitro group and one or two (preferably one) C 1-6 alkoxy groups (preferably methoxy, ethoxy), or
(2) indanyl;
Of R 2b , R 3b , R 4b and R 5b , R 3b or R 4b is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms; and R 6b is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl),
Compound (Ib).

［化合物Ｃ１］
環Ａｃが、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｃが、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ｃが、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基である、
化合物（Ｉｃ）。 [Compound C1]
Ring Ac is a pyrrolidine ring, piperidine ring or azepane ring;
R 1c is an optionally substituted C 6-10 aryl group (preferably phenyl);
At least one of R 2c , R 3c , R 4c and R 5c is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted be a C 1-6 alkyl group be a (preferably methyl); and R 6c is an optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group or a substituted, An optionally substituted C 6-10 aryl-C 2-6 alkenyl group,
Compound (Ic).

［化合物Ｃ２］
環Ａｃが、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｃが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）であり；かつ
Ｒ６ｃが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、Ｃ６－１４アリール基（好ましくはフェニル）、Ｃ７－１６アラルキル基（好ましくはベンジル）またはＣ６－１０アリール－Ｃ２－６アルケニル基（好ましくは３－フェニル－２－プロペニル）である、
化合物（Ｉｃ）。 [Compound C2]
Ring Ac is a pyrrolidine ring, piperidine ring or azepane ring;
R 1c is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
At least one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably And a C 6-14 aryl group (preferably phenyl), a C 7-16 aralkyl group (preferably phenyl), and R 6c each optionally substituted with a C 1-6 alkyl group (preferably methyl). Is benzyl) or a C 6-10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl),
Compound (Ic).

［化合物Ｃ３］
環Ａｃが、ピペリジン環であり；
Ｒ１ｃが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ｃが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ７－１６アラルキル基（好ましくはベンジル）、またはＣ６－１０アリール－Ｃ２－６アルケニル基（好ましくは３－フェニル－２－プロペニル）である、
化合物（Ｉｃ）。 [Compound C3]
Ring Ac is a piperidine ring;
R 1c is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
One of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms; and R 6c is a C 1-6 alkyl group (preferably Is a C 6-10 aryl group (preferably phenyl) optionally substituted with methyl), a C 7-16 aralkyl group (preferably benzyl) optionally substituted with a C 1-6 alkyl group (preferably methyl) Or a C 6-10 aryl-C 2-6 alkenyl group (preferably 3-phenyl-2-propenyl),
Compound (Ic).

［化合物Ｃ４］
環Ａｃが、ピペリジン環であり；
Ｒ１ｃが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃのうち、Ｒ３ｃまたはＲ４ｃがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；かつ
Ｒ６ｃが、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）である、
化合物（Ｉｃ）。 [Compound C4]
Ring Ac is a piperidine ring;
R 1c is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
Of R 2c , R 3c , R 4c and R 5c , R 3c or R 4c is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms; and R 6c is C 1 A C 6-10 aryl group (preferably phenyl) substituted with a -6 alkyl group (preferably methyl),
Compound (Ic).

［化合物Ｄ１］
環Ａｄが、それぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｄが、置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの少なくとも１つが置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子または置換されていてもよいＣ１－６アルキル基（好ましくはメチル）であり；
Ｒ６ｄが、置換されていてもよいＣ６－１４アリール基であり；かつ
ｎｄが、１ないし５の整数である、
化合物（Ｉｄ）。 [Compound D1]
Ring Ad is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted;
R 1d is an optionally substituted C 6-10 aryl group (preferably phenyl);
At least one of R 2d , R 3d , R 4d and R 5d is an optionally substituted C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a substituted An optionally substituted C 1-6 alkyl group (preferably methyl);
R 6d is an optionally substituted C 6-14 aryl group; and nd is an integer of 1 to 5,
Compound (Id).

［化合物Ｄ２］
環Ａｄが、Ｃ１－６アルキル基（好ましくはメチル）でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環であり；
Ｒ１ｄが、ニトロ基で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの少なくとも１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基（好ましくはメチル）であり；
Ｒ６ｄが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１４アリール基（好ましくはフェニル）であり；かつ
ｎｄが、１ないし５の整数である、
化合物（Ｉｄ）。 [Compound D2]
Ring Ad is a pyrrolidine ring, piperidine ring or azepane ring, each optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1d is a C 6-10 aryl group (preferably phenyl) optionally substituted with a nitro group;
At least one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl), and the rest are each independently a hydrogen atom or a C 1-6 alkyl group (preferably Methyl);
R 6d is a C 6-14 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl); and nd is an integer of 1 to 5,
Compound (Id).

［化合物Ｄ３］
環Ａｄが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいピペリジン環であり；
Ｒ１ｄが、Ｃ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの１つがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；
Ｒ６ｄが、Ｃ１－６アルキル基（好ましくはメチル）で置換されていてもよいＣ６－１０アリール基（好ましくはフェニル）であり；かつ
ｎｄが、１ないし３の整数（好ましくは３）である、
化合物（Ｉｄ）。 [Compound D3]
Ring Ad is a piperidine ring optionally substituted with a C 1-6 alkyl group (preferably methyl);
R 1d is a C 6-10 aryl group (preferably phenyl);
One of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group (preferably methyl) and the remaining three are hydrogen atoms;
R 6d is a C 6-10 aryl group (preferably phenyl) optionally substituted with a C 1-6 alkyl group (preferably methyl); and n d is an integer of 1 to 3 (preferably 3 )
Compound (Id).

［化合物Ｄ４］
環Ａｄが、ピペリジン環であり；
Ｒ１ｄが、Ｃ６－１０アリール基（好ましくはフェニル）であり；
Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄのうち、Ｒ３ｄまたはＲ４ｄがＣ１－６アルキル基（好ましくはメチル）であり、かつ残り３つが水素原子であり；
Ｒ６ｄが、Ｃ１－６アルキル基（好ましくはメチル）で置換されたＣ６－１０アリール基（好ましくはフェニル）であり；かつ
ｎｄが、１ないし３の整数（好ましくは３）である、
化合物（Ｉｄ）。 [Compound D4]
Ring Ad is a piperidine ring;
R 1d is a C 6-10 aryl group (preferably phenyl);
Of R 2d , R 3d , R 4d and R 5d , R 3d or R 4d is a C 1-6 alkyl group (preferably methyl), and the remaining three are hydrogen atoms;
R 6d is a C 6-10 aryl group (preferably phenyl) substituted with a C 1-6 alkyl group (preferably methyl); and nd is an integer of 1 to 3 (preferably 3) ,
Compound (Id).

［化合物Ｅ］ [Compound E]

実施例１の化合物 Compound of Example 1

Figure JPOXMLDOC01-appb-C000019
Figure JPOXMLDOC01-appb-C000019

実施例２の化合物 Compound of Example 2

Figure JPOXMLDOC01-appb-C000020
Figure JPOXMLDOC01-appb-C000020

実施例３の化合物 Compound of Example 3

Figure JPOXMLDOC01-appb-C000021
Figure JPOXMLDOC01-appb-C000021

実施例５の化合物 Compound of Example 5

Figure JPOXMLDOC01-appb-C000022
Figure JPOXMLDOC01-appb-C000022

実施例２３の化合物 Compound of Example 23

Figure JPOXMLDOC01-appb-C000023
Figure JPOXMLDOC01-appb-C000023

実施例２５の化合物 Compound of Example 25

Figure JPOXMLDOC01-appb-C000024
Figure JPOXMLDOC01-appb-C000024

実施例３４の化合物 Compound of Example 34

Figure JPOXMLDOC01-appb-C000025
Figure JPOXMLDOC01-appb-C000025

実施例８３の化合物 Example 83 Compound

Figure JPOXMLDOC01-appb-C000026
Figure JPOXMLDOC01-appb-C000026

実施例８６の化合物 Example 86 Compound

Figure JPOXMLDOC01-appb-C000027
Figure JPOXMLDOC01-appb-C000027

　化合物（Ｉａ）、化合物（Ｉｂ）、化合物（Ｉｃ）、化合物（Ｉｄ）または化合物（Ｉ）（以下、これらをまとめて化合物（Ｉ）ともいう）が塩である場合、そのような塩としては、例えば、金属塩、アンモニウム塩、有機塩基との塩、無機酸との塩、有機酸との塩、塩基性または酸性アミノ酸との塩等が挙げられる。金属塩の好適な例としては、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩；カルシウム塩、マグネシウム塩、バリウム塩等のアルカリ土類金属塩；アルミニウム塩等が挙げられる。有機塩基との塩の好適な例としては、例えば、トリメチルアミン、トリエチルアミン、ピリジン、ピコリン、２，６－ルチジン、エタノールアミン、ジエタノールアミン、トリエタノールアミン、シクロヘキシルアミン、ジシクロヘキシルアミン、Ｎ，Ｎ'－ジベンジルエチレンジアミン等との塩が挙げられる。無機酸との塩の好適な例としては、例えば、塩酸、臭化水素酸、硝酸、硫酸、リン酸等との塩が挙げられる。有機酸との塩の好適な例としては、例えば、ギ酸、酢酸、トリフルオロ酢酸、フタル酸、フマル酸、シュウ酸、酒石酸、マレイン酸、クエン酸、コハク酸、リンゴ酸、メタンスルホン酸、ベンゼンスルホン酸、ｐ－トルエンスルホン酸等との塩が挙げられる。塩基性アミノ酸との塩の好適な例としては、例えば、アルギニン、リジン、オルニチン等との塩が挙げられ、酸性アミノ酸との塩の好適な例としては、例えば、アスパラギン酸、グルタミン酸等との塩が挙げられる。
　このうち、薬学的に許容し得る塩が好ましい。例えば、化合物内に酸性官能基を有する場合には、アルカリ金属塩（例、ナトリウム塩、カリウム塩等）、アルカリ土類金属塩（例、カルシウム塩、マグネシウム塩等）等の無機塩、アンモニウム塩等、また、化合物内に塩基性官能基を有する場合には、例えば、塩酸、臭化水素酸、硝酸、硫酸、リン酸等の無機酸との塩、または酢酸、フタル酸、フマル酸、シュウ酸、酒石酸、マレイン酸、クエン酸、コハク酸、メタンスルホン酸、ベンゼンスルホン酸、ｐ－トルエンスルホン酸等の有機酸との塩が挙げられる。 When compound (Ia), compound (Ib), compound (Ic), compound (Id) or compound (I) (hereinafter collectively referred to as compound (I)) is a salt, Examples thereof include metal salts, ammonium salts, salts with organic bases, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids, and the like. Preferable examples of the metal salt include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt, magnesium salt and barium salt; aluminum salt and the like. Preferable examples of the salt with organic base include, for example, trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N, N′-dibenzyl. Examples include salts with ethylenediamine and the like. Preferable examples of the salt with inorganic acid include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like. Preferable examples of the salt with organic acid include, for example, formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzene Examples thereof include salts with sulfonic acid, p-toluenesulfonic acid and the like. Preferable examples of salts with basic amino acids include salts with arginine, lysine, ornithine and the like, and preferable examples of salts with acidic amino acids include salts with aspartic acid, glutamic acid and the like. Is mentioned.
Of these, pharmaceutically acceptable salts are preferred. For example, when the compound has an acidic functional group, inorganic salts such as alkali metal salts (eg, sodium salts, potassium salts, etc.), alkaline earth metal salts (eg, calcium salts, magnesium salts, etc.), ammonium salts In addition, when the compound has a basic functional group, for example, a salt with an inorganic acid such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, or acetic acid, phthalic acid, fumaric acid, And salts with organic acids such as acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

　以下、本発明化合物の製造法について説明する。
　化合物（Ｉ）の製造法の例として、代表的な製造法を以下に述べるが、製造法はこれらに限定されない。
　化合物（Ｉ）は下記の製造ルート（１）または（２）で示される方法またはそれに準じた方法等により製造することもできる。化合物（Ｉａ）、化合物（Ｉｂ）、化合物（Ｉｃ）および化合物（Ｉｄ）は、化合物（Ｉ）と同様の方法により製造できる。 Hereafter, the manufacturing method of this invention compound is demonstrated.
As examples of the production method of compound (I), typical production methods are described below, but the production methods are not limited to these.
Compound (I) can also be produced by the method shown in the following production route (1) or (2) or a method analogous thereto. Compound (Ia), compound (Ib), compound (Ic) and compound (Id) can be produced by the same method as for compound (I).

　各原料化合物は反応を阻害しないのであれば、塩を形成していてもよく、かかる塩としては、化合物（Ｉ）の塩と同様のものが挙げられる。
　原料化合物は具体的製法を述べない場合、市販されているものを容易に入手して用いることができるか、または自体公知の方法、またはそれに準ずる方法に従って製造することもできる。 Each raw material compound may form a salt as long as it does not inhibit the reaction. Examples of such a salt include the same salts as the salt of compound (I).
In the case where a specific production method is not described, a raw material compound can be easily obtained and used commercially, or can be produced according to a method known per se or a method analogous thereto.

　化合物（Ｉ）は反応式１～２により製造することができる。 Compound (I) can be produced according to Reaction Schemes 1-2.

Figure JPOXMLDOC01-appb-C000028
Figure JPOXMLDOC01-appb-C000028

（式中、Ｐ１は、カルボキシ基の保護基を示し、その他の記号は前記と同義である。）
　Ｐ１で示される「カルボキシ基の保護基」としては、Ｃ１－６アルキル基（メチル、エチル、ｎ－プロピル、イソプロピル、ｎ－ブチル、ｔｅｒｔ－ブチルなど）、フェニル基、トリチル基、シリル基などが挙げられ、これらの保護基は置換基を有していてもよい。これらの置換基としては、例えば、ハロゲン原子（フッ素原子、塩素原子、臭素原子、ヨウ素原子など）、ホルミル基、Ｃ１－６アルキル－カルボニル基（アセチル、プロピオニル、ブチルカルボニルなど）、ニトロ基などが挙げられ、置換基の数は１～３個程度である。好ましくは、Ｃ１－６アルキル基であり、特に好ましくは、メチル、エチルである。 (Wherein P 1 represents a protecting group for a carboxy group, and other symbols are as defined above.)
Examples of the “carboxy-protecting group” represented by P 1 include a C 1-6 alkyl group (methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.), phenyl group, trityl group, silyl group These protecting groups may have a substituent. Examples of these substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), formyl groups, C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups, etc. The number of substituents is about 1 to 3. A C 1-6 alkyl group is preferred, and methyl and ethyl are particularly preferred.

工程１
　この工程は、化合物（１）を、縮合剤の存在下、化合物（２）と溶媒中で反応させることにより、化合物（３）を得る工程である。
　化合物（２）の使用量は、化合物（１）に対して、通常１～２当量、好ましくは１～１．２当量である。
　縮合剤としては、ジシクロヘキシルカルボジイミド（ＤＣＣ）、１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（ＥＤＣ・ＨＣｌ）等が挙げられる。縮合剤の使用量は、化合物（１）に対して、通常１～２当量、好ましくは１～１．２当量である。
　必要に応じて、縮合促進剤等や塩基の存在下に反応を行ってもよい。
　縮合促進剤としては、１－ヒドロキシベンゾトリアゾール（ＨＯＢｔ）一水和物等が挙げられる。縮合促進剤の使用量は、化合物（１）に対して、通常１～２当量、好ましくは１～１．２当量である。
　塩基としては、トリエチルアミン、Ｎ，Ｎ－ジイソプロピルエチルアミン、４－（ジメチルアミノ）ピリジン（ＤＭＡＰ）、ピリジン等の有機塩基が挙げられる。塩基の使用量は、化合物（１）に対して、通常０．１～２当量、好ましくは０．１～１．２当量である。
　溶媒としては、塩化メチレン、Ｎ，Ｎ－ジメチルホルムアミド、クロロホルム等が挙げられる。
　反応温度は、通常０～３５℃、好ましくは１５～２５℃であり、反応時間は通常１～２４時間である。 Process 1
This step is a step of obtaining compound (3) by reacting compound (1) with compound (2) in a solvent in the presence of a condensing agent.
The amount of compound (2) to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (1).
Examples of the condensing agent include dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC · HCl), and the like. The amount of the condensing agent to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (1).
If necessary, the reaction may be carried out in the presence of a condensation accelerator or the like or a base.
Examples of the condensation accelerator include 1-hydroxybenzotriazole (HOBt) monohydrate. The amount of the condensation accelerator used is usually 1 to 2 equivalents, preferably 1 to 1.2 equivalents, relative to compound (1).
Examples of the base include organic bases such as triethylamine, N, N-diisopropylethylamine, 4- (dimethylamino) pyridine (DMAP), and pyridine. The amount of the base to be used is generally 0.1-2 equivalents, preferably 0.1-1.2 equivalents, relative to compound (1).
Examples of the solvent include methylene chloride, N, N-dimethylformamide, chloroform and the like.
The reaction temperature is usually 0 to 35 ° C., preferably 15 to 25 ° C., and the reaction time is usually 1 to 24 hours.

　あるいは、化合物（１）を、ハロゲン化剤を用いて酸ハロゲン化物に変換した後、塩基の存在下、化合物（２）と溶媒中で反応させることにより、化合物（３）を製造することもできる。
　化合物（２）の使用量は、化合物（１）に対して、通常１～２当量、好ましくは１～１．２当量である。
　ハロゲン化剤としては、塩化チオニル、塩化オキザリル、三塩化リン、塩化スルフリル等が挙げられる。ハロゲン化剤の使用量は、化合物（１）に対して、通常１～５当量、好ましくは１～２当量である。
　塩基としては、トリエチルアミン、Ｎ，Ｎ－ジイソプロピルエチルアミン、ピリジン等の有機塩基が挙げられる。塩基の使用量は、化合物（１）に対して、通常１～２当量、好ましくは１～１．２当量である。
　溶媒としては、塩化メチレン、クロロホルム、トルエン、テトラヒドロフラン等が挙げられる。
　反応温度は、通常０～４５℃、好ましくは０～２５℃であり、反応時間は通常１～２４時間である。 Alternatively, compound (3) can be produced by converting compound (1) to an acid halide using a halogenating agent and then reacting with compound (2) in a solvent in the presence of a base. .
The amount of compound (2) to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (1).
Examples of the halogenating agent include thionyl chloride, oxalyl chloride, phosphorus trichloride, sulfuryl chloride and the like. The amount of the halogenating agent to be used is generally 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to compound (1).
Examples of the base include organic bases such as triethylamine, N, N-diisopropylethylamine, and pyridine. The amount of the base to be used is generally 1 to 2 equivalents, preferably 1 to 1.2 equivalents, relative to compound (1).
Examples of the solvent include methylene chloride, chloroform, toluene, tetrahydrofuran and the like.
The reaction temperature is usually 0 to 45 ° C., preferably 0 to 25 ° C., and the reaction time is usually 1 to 24 hours.

工程２
　この工程は、化合物（３）を脱保護して、化合物（４）を得る工程である。脱保護は、例えば、化合物（３）を塩基と溶媒中で反応させることによって行われる。
　塩基としては、水酸化ナトリウム、水酸化カリウム、水酸化リチウム等が挙げられる。塩基の使用量は、化合物（３）に対して、通常１～２当量、好ましくは１～１．２当量である。
　溶媒としては、例えば、メタノール、エタノール、テトラヒドロフラン、１，４－ジオキサン等が挙げられる。これらは、水と適宜の割合で混合して用いるのが好ましい。
　反応温度は、通常０～８０℃、好ましくは１５～２５℃であり、反応時間は通常１～２４時間である。 Process 2
This step is a step of obtaining compound (4) by deprotecting compound (3). Deprotection is performed, for example, by reacting compound (3) with a base in a solvent.
Examples of the base include sodium hydroxide, potassium hydroxide, lithium hydroxide and the like. The amount of the base to be used is generally 1-2 equivalents, preferably 1-1.2 equivalents, relative to compound (3).
Examples of the solvent include methanol, ethanol, tetrahydrofuran, 1,4-dioxane and the like. These are preferably used by mixing with water at an appropriate ratio.
The reaction temperature is usually 0 to 80 ° C., preferably 15 to 25 ° C., and the reaction time is usually 1 to 24 hours.

工程３
　この工程は、化合物（４）と化合物（５）を反応させて、化合物（Ｉ）を得る工程である。
　当該工程は、製造ルート（１）の工程１と同様の方法により行われる。 Process 3
This step is a step in which compound (I) is obtained by reacting compound (4) with compound (5).
This step is performed by the same method as in step 1 of the manufacturing route (1).

（式中、Ｐ２は、アミノ基の保護基を示し、その他の記号は前記と同義である。）
　Ｐ２で示される「アミノ基の保護基」としては、ホルミル基、Ｃ１－６アルキル－カルボニル基（アセチル、プロピオニルなど）、フェニルカルボニル基、Ｃ１－６アルキル－オキシカルボニル基（メトキシカルボニル、エトキシカルボニル、ｔｅｒｔ－ブトキシカルボニルなど）、アリールオキシカルボニル基（フェニルオキシカルボニルなど）、Ｃ７－１０アラルキル－カルボニル基（ベンジルオキシカルボニルなど）、ベンジル基、ベンズヒドリル基、トリチル基、フタロイル基などが挙げられ、これらの保護基は置換基を有していてもよい。これらの置換基としては、例えば、ハロゲン原子（フッ素原子、塩素原子、臭素原子、ヨウ素原子など）、Ｃ１－６アルキル－カルボニル基（アセチル、プロピオニル、ブチルカルボニルなど）、ニトロ基などが挙げられ、置換基の数は１～３個程度である。好ましくは、ｔｅｒｔ－ブトキシカルボニル、ベンジルオキシカルボニルである。 (Wherein P 2 represents an amino-protecting group, and other symbols are as defined above.)
Examples of the “amino-protecting group” represented by P 2 include a formyl group, a C 1-6 alkyl-carbonyl group (acetyl, propionyl, etc.), a phenylcarbonyl group, a C 1-6 alkyl-oxycarbonyl group (methoxycarbonyl, Ethoxycarbonyl, tert-butoxycarbonyl etc.), aryloxycarbonyl group (phenyloxycarbonyl etc.), C 7-10 aralkyl-carbonyl group (benzyloxycarbonyl etc.), benzyl group, benzhydryl group, trityl group, phthaloyl group etc. These protecting groups may have a substituent. Examples of these substituents include halogen atoms (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups and the like. The number of substituents is about 1 to 3. Preferred are tert-butoxycarbonyl and benzyloxycarbonyl.

工程１
　この工程は、化合物（６）と化合物（５）を反応させて、化合物（７）を得る工程である。
　当該工程は、製造ルート（１）の工程１と同様の方法により行われる。 Process 1
This step is a step of obtaining the compound (7) by reacting the compound (6) with the compound (5).
This step is performed by the same method as in step 1 of the manufacturing route (1).

工程２
　この工程は、化合物（７）を脱保護して、化合物（８）を得る工程である。脱保護は、例えば、Ｐ２がｔｅｒｔ－ブトキシカルボニル等の場合、化合物（７）を酸と溶媒中で反応させることによって行われる。
　酸としては、塩酸、トリフルオロ酢酸（ＴＦＡ）、ギ酸等が挙げられる。酸の使用量は、化合物（７）に対して、通常２～１００当量、好ましくは５～１０当量である。
　溶媒としては、例えば、１，４－ジオキサン、テトラヒドロフラン、酢酸エチル等が挙げられる。
　反応温度は、通常０～３５℃、好ましくは１５～２５℃であり、反応時間は通常１～２４時間である。
　また、Ｐ２がｔｅｒｔ－ブトキシカルボニル等以外の場合、脱保護は、公知、またはWiley-Interscience社１９９９年刊「Protective Groups in Organic Synthesis, 3rd Ed.」（Theodora W. Greene, Peter G. M. Wuts著）などに記載されている方法、あるいはそれに準じる方法により行われる。 Process 2
This step is a step of obtaining compound (8) by deprotecting compound (7). Deprotection is performed, for example, by reacting compound (7) with an acid in a solvent when P 2 is tert-butoxycarbonyl or the like.
Examples of the acid include hydrochloric acid, trifluoroacetic acid (TFA), formic acid and the like. The amount of the acid to be used is generally 2-100 equivalents, preferably 5-10 equivalents, relative to compound (7).
Examples of the solvent include 1,4-dioxane, tetrahydrofuran, ethyl acetate and the like.
The reaction temperature is usually 0 to 35 ° C., preferably 15 to 25 ° C., and the reaction time is usually 1 to 24 hours.
Further, when P 2 is other than such tert- butoxycarbonyl, deprotection, known or described in Wiley-Interscience, 1999, "Protective Groups in Organic Synthesis, 3 rd Ed. " (Theodora W. Greene, Peter GM Wuts Author) It is performed by the method described in the above, or the method according to it.

工程３
　この工程は、化合物（８）と化合物（２）を反応させて、化合物（Ｉ）を得る工程である。
　当該工程は、製造ルート（１）の工程１と同様の方法により行われる。 Process 3
In this step, compound (8) and compound (2) are reacted to obtain compound (I).
This step is performed by the same method as in step 1 of the manufacturing route (1).

　原料化合物である化合物（１）、（２）、（５）および（６）は市販品を用いるか、あるいは自体公知の方法により製造することができる。 Compounds (1), (2), (5) and (6) which are raw material compounds can be commercially available or can be produced by a method known per se.

　目的化合物および原料合成の各反応において、原料化合物が置換基としてアミノ基、カルボキシ基、ヒドロキシ基を有する場合、これらの基は、ペプチド化学などで一般的に使用されるような保護基で保護されていてもよい。この場合、反応後に、必要に応じて、保護基を除去することにより目的化合物を得ることができる。 In each reaction of the target compound and raw material synthesis, when the raw material compound has an amino group, a carboxy group, or a hydroxy group as a substituent, these groups are protected with a protecting group that is generally used in peptide chemistry and the like. It may be. In this case, the target compound can be obtained by removing the protecting group as necessary after the reaction.

　このような保護基としては、例えば、Wiley-Interscience社１９９９年刊「ProtectiveGroups in Organic Synthesis, 3rd Ed.」（Theodora W. Greene, Peter G. M. Wuts著）に記載されているものが挙げられる。 Examples of such protecting groups, e.g., Wiley-Interscience, Inc. 1999 annual "ProtectiveGroups in Organic Synthesis, 3 rd Ed . " (Theodora W. Greene, Peter G. M. Wuts Author) include those described in.

　アミノ基の保護基としては、例えば、ホルミル基、Ｃ１－６アルキル－カルボニル基（アセチル、プロピオニルなど）、フェニルカルボニル基、Ｃ１－６アルキル－オキシカルボニル基（メトキシカルボニル、エトキシカルボニル、tert-ブトキシカルボニルなど）、アリールオキシカルボニル基（フェニルオキシカルボニルなど）、Ｃ７－１０アラルキル－カルボニル基（ベンジルオキシカルボニルなど）、ベンジル基、ベンズヒドリル基、トリチル基、フタロイル基などが挙げられ、これらの保護基は置換基を有していてもよい。これらの置換基としては、例えば、ハロゲン原子（フッ素原子、塩素原子、臭素原子、ヨウ素原子など）、Ｃ１－６アルキル－カルボニル基（アセチル、プロピオニル、ブチルカルボニルなど）、ニトロ基などが挙げられ、置換基の数は１～３個程度である。 Examples of the protecting group for amino group include formyl group, C 1-6 alkyl-carbonyl group (acetyl, propionyl, etc.), phenylcarbonyl group, C 1-6 alkyl-oxycarbonyl group (methoxycarbonyl, ethoxycarbonyl, tert- Butoxycarbonyl group, etc.), aryloxycarbonyl group (phenyloxycarbonyl etc.), C 7-10 aralkyl-carbonyl group (benzyloxycarbonyl etc.), benzyl group, benzhydryl group, trityl group, phthaloyl group, etc. The group may have a substituent. Examples of these substituents include halogen atoms (fluorine atom, chlorine atom, bromine atom, iodine atom, etc.), C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups and the like. The number of substituents is about 1 to 3.

　カルボキシ基の保護基としては、例えば、Ｃ１－６アルキル基（メチル、エチル、ｎ－プロピル、イソプロピル、ｎ－ブチル、ｔｅｒｔ－ブチルなど）、フェニル基、トリチル基、シリル基などが挙げられ、これらの保護基は置換基を有していてもよい。これらの置換基としては、例えば、ハロゲン原子（フッ素原子、塩素原子、臭素原子、ヨウ素原子など）、ホルミル基、Ｃ１－６アルキル－カルボニル基（アセチル、プロピオニル、ブチルカルボニルなど）、ニトロ基などが挙げられ、置換基の数は１～３個程度である。 Examples of the protecting group for the carboxy group include a C 1-6 alkyl group (methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.), a phenyl group, a trityl group, a silyl group, and the like. These protecting groups may have a substituent. Examples of these substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), formyl groups, C 1-6 alkyl-carbonyl groups (acetyl, propionyl, butylcarbonyl, etc.), nitro groups, etc. The number of substituents is about 1 to 3.

　ヒドロキシ基の保護基としては、例えば、Ｃ１－６アルキル基（メチル、エチル、ｎ－プロピル、イソプロピル、ｎ－ブチル、ｔｅｒｔ－ブチルなど）、フェニル基、Ｃ７－１０アラルキル基（ベンジルなど）、ホルミル基、Ｃ１－６アルキル－カルボニル基（アセチル、プロピオニルなど）、アリールオキシカルボニル基（フェニルオキシカルボニルなど）、Ｃ７－１０アラルキル－カルボニル基（ベンジルオキシカルボニルなど）、ピラニル基、フラニル基、シリル基などが挙げられ、これらの保護基は置換基を有していてもよい。これらの置換基としては、例えば、ハロゲン原子（フッ素原子、塩素原子、臭素原子、ヨウ素原子など）、Ｃ１－６アルキル基、フェニル基、Ｃ７－１０アラルキル基、ニトロ基などが挙げられ、置換基の数は１～４個程度である。 Examples of the protecting group for the hydroxy group include C 1-6 alkyl groups (methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.), phenyl groups, C 7-10 aralkyl groups (benzyl, etc.) , Formyl group, C 1-6 alkyl-carbonyl group (acetyl, propionyl etc.), aryloxycarbonyl group (phenyloxycarbonyl etc.), C 7-10 aralkyl-carbonyl group (benzyloxycarbonyl etc.), pyranyl group, furanyl group , A silyl group, and the like, and these protective groups may have a substituent. Examples of these substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), C 1-6 alkyl groups, phenyl groups, C 7-10 aralkyl groups, nitro groups, and the like. The number of substituents is about 1 to 4.

　保護基の除去は、公知またはWiley-Interscience社１９９９年刊「Protective Groups in Organic Synthesis, 3rd Ed.」（Theodora W. Greene, Peter G. M. Wuts著）などに記載されている方法、あるいはそれに準じる方法により行うことができる。例えば、酸、塩基、還元、紫外光、ヒドラジン、フェニルヒドラジン、Ｎ－メチルジチオカルバミン酸ナトリウム、テトラブチルアンモニウムフルオリド、酢酸パラジウムなどで処理する方法が利用できる。 Removal of the protecting groups, known or Wiley-Interscience, 1999, "Protective Groups in Organic Synthesis, 3 rd Ed. " (Theodora W. Greene, Peter GM Wuts Author) methods are described in, for example, or by methods analogous thereto It can be carried out. For example, a method of treating with acid, base, reduction, ultraviolet light, hydrazine, phenylhydrazine, sodium N-methyldithiocarbamate, tetrabutylammonium fluoride, palladium acetate or the like can be used.

　上記の方法において化合物（Ｉ）が遊離化合物として得られる場合、常法に従って、例えば、無機酸（塩酸、硫酸、臭化水素酸など）、有機酸（メタンスルホン酸、ベンゼンスルホン酸、トルエンスルホン酸、シュウ酸、フマル酸、マレイン酸、酒石酸など）、無機塩基（ナトリウム、カリウムなどのアルカリ金属、カルシウム、マグネシウムなどのアルカリ土類金属、アルミニウムまたはアンモニウムなど）または有機塩基（トリメチルアミン、トリエチルアミン、ピリジン、ピコリン、エタノールアミン、ジエタノールアミン、トリエタノールアミン、ジシクロヘキシルアミンまたはＮ，Ｎ’－ジベンジルエチレンジアミンなど）などとの塩を生成させることもでき、化合物（Ｉ）が塩の形態で得られる場合は、常法に従って、遊離の化合物または他の塩に変換することもできる。 When compound (I) is obtained as a free compound in the above method, according to a conventional method, for example, inorganic acid (hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acid (methanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid) , Oxalic acid, fumaric acid, maleic acid, tartaric acid, etc.), inorganic bases (alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, aluminum or ammonium) or organic bases (trimethylamine, triethylamine, pyridine, A salt with picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine or N, N′-dibenzylethylenediamine, etc.) can be formed. When compound (I) is obtained in the form of a salt, According to the law, free It can also be converted to compounds or other salts.

　また、前記の各反応において、原料化合物が塩を形成し得る場合、該化合物を塩として用いてもよい。このような塩としては、例えば化合物（Ｉ）の塩として例示したものが使用される。 In each of the reactions described above, when the raw material compound can form a salt, the compound may be used as a salt. As such a salt, for example, those exemplified as the salt of compound (I) are used.

　このような方法により生成した本発明の化合物（Ｉ）は、例えば、再結晶、蒸留、クロマトグラフィーなどの通常の分離手段により単離、精製することができる。 The compound (I) of the present invention produced by such a method can be isolated and purified by usual separation means such as recrystallization, distillation, chromatography and the like.

　化合物（Ｉ）が、光学異性体、立体異性体、位置異性体、回転異性体を含有する場合には、これらも化合物（Ｉ）として含有されるとともに、自体公知の合成手法、分離手法（濃縮、溶媒抽出、カラムクロマトグラフィー、再結晶など）によりそれぞれを単品として得ることができる。例えば、化合物（Ｉ）に光学異性体が存在する場合には、該化合物から分割された光学異性体も化合物（Ｉ）に包含される。 When compound (I) contains optical isomers, stereoisomers, positional isomers, and rotational isomers, these are also included as compound (I), as well as synthetic methods and separation methods known per se (concentration). , Solvent extraction, column chromatography, recrystallization, etc.), each can be obtained as a single product. For example, when compound (I) has an optical isomer, the optical isomer resolved from the compound is also encompassed in compound (I).

　光学異性体は自体公知の方法により製造することができる。具体的には、光学活性な合成中間体を用いる、または、最終物のラセミ体を常法に従って光学分割することにより光学異性体を得る。 The optical isomer can be produced by a method known per se. Specifically, an optical isomer is obtained by using an optically active synthetic intermediate or by optically resolving the final racemate according to a conventional method.

　化合物（Ｉ）は結晶であってもよく、結晶形が単一であっても結晶形混合物であっても化合物（Ｉ）に包含される。結晶は、自体公知の結晶化法を適用して、結晶化することによって製造することができる。
　化合物（Ｉ）は、水和物、非水和物、溶媒和物、無溶媒和物のいずれであってもよい。 Compound (I) may be a crystal, and it is included in compound (I) regardless of whether the crystal form is a single crystal form or a mixture of crystal forms. The crystal can be produced by crystallization by applying a crystallization method known per se.
Compound (I) may be a hydrate, a non-hydrate, a solvate, or a non-solvate.

　本発明化合物は、毒性が低く、そのまま、または薬理学的に許容し得る担体等と混合して医薬組成物とすることにより、哺乳動物（例、ヒト、マウス、ラット、ウサギ、イヌ、ネコ、ウシ、ウマ、ブタ、サル）に対して、後述する各種疾患の予防または治療剤として用いることができる。 The compound of the present invention has low toxicity and is used as it is or mixed with a pharmacologically acceptable carrier to make a pharmaceutical composition, so that a mammal (eg, human, mouse, rat, rabbit, dog, cat, Cattle, horses, pigs, monkeys) can be used as preventive or therapeutic agents for various diseases described below.

　ここにおいて、薬理学的に許容し得る担体としては、製剤素材として慣用の各種有機あるいは無機担体物質が用いられ、固形製剤における賦形剤、滑沢剤、結合剤、崩壊剤；液状製剤における溶剤、溶解補助剤、懸濁化剤、等張化剤、緩衝剤、無痛化剤等として配合される。また必要に応じて、防腐剤、抗酸化剤、着色剤、甘味剤等の製剤添加物を用いることもできる。 Here, as the pharmacologically acceptable carrier, various organic or inorganic carrier substances commonly used as pharmaceutical materials are used, and excipients, lubricants, binders, disintegrants in solid preparations; solvents in liquid preparations , Solubilizing agents, suspending agents, isotonic agents, buffers, soothing agents and the like. If necessary, preparation additives such as preservatives, antioxidants, colorants, sweeteners and the like can also be used.

　賦形剤の好適な例としては、乳糖、白糖、Ｄ－マンニトール、Ｄ－ソルビトール、デンプン、α化デンプン、デキストリン、結晶セルロース、低置換度ヒドロキシプロピルセルロース、カルボキシメチルセルロースナトリウム、アラビアゴム、プルラン、軽質無水ケイ酸、合成ケイ酸アルミニウム、メタケイ酸アルミン酸マグネシウムが挙げられる。 Preferable examples of excipients include lactose, sucrose, D-mannitol, D-sorbitol, starch, pregelatinized starch, dextrin, crystalline cellulose, low-substituted hydroxypropylcellulose, sodium carboxymethylcellulose, gum arabic, pullulan, light Examples thereof include anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminate metasilicate.

　滑沢剤の好適な例としては、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク、コロイドシリカが挙げられる。 Preferable examples of the lubricant include magnesium stearate, calcium stearate, talc and colloidal silica.

　結合剤の好適な例としては、α化デンプン、ショ糖、ゼラチン、アラビアゴム、メチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、結晶セルロース、白糖、Ｄ－マンニトール、トレハロース、デキストリン、プルラン、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルピロリドンが挙げられる。 Preferred examples of the binder include pregelatinized starch, sucrose, gelatin, gum arabic, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, sucrose, D-mannitol, trehalose, dextrin, pullulan, hydroxypropylcellulose, hydroxy Examples include propylmethylcellulose and polyvinylpyrrolidone.

　崩壊剤の好適な例としては、乳糖、白糖、デンプン、カルボキシメチルセルロース、カルボキシメチルセルロースカルシウム、クロスカルメロースナトリウム、カルボキシメチルスターチナトリウム、軽質無水ケイ酸、低置換度ヒドロキシプロピルセルロースが挙げられる。 Preferable examples of the disintegrant include lactose, sucrose, starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, croscarmellose sodium, carboxymethyl starch sodium, light anhydrous silicic acid, and low-substituted hydroxypropyl cellulose.

　溶剤の好適な例としては、注射用水、生理的食塩水、リンゲル液、アルコール、プロピレングリコール、ポリエチレングリコール、ゴマ油、トウモロコシ油、オリーブ油、綿実油が挙げられる。 Suitable examples of the solvent include water for injection, physiological saline, Ringer's solution, alcohol, propylene glycol, polyethylene glycol, sesame oil, corn oil, olive oil, and cottonseed oil.

　溶解補助剤の好適な例としては、ポリエチレングリコール、プロピレングリコール、Ｄ－マンニトール、トレハロース、安息香酸ベンジル、エタノール、トリスアミノメタン、コレステロール、トリエタノールアミン、炭酸ナトリウム、クエン酸ナトリウム、サリチル酸ナトリウム、酢酸ナトリウムが挙げられる。 Preferable examples of the solubilizer include polyethylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate. Is mentioned.

　懸濁化剤の好適な例としては、ステアリルトリエタノールアミン、ラウリル硫酸ナトリウム、ラウリルアミノプロピオン酸、レシチン、塩化ベンザルコニウム、塩化ベンゼトニウム、モノステアリン酸グリセリン等の界面活性剤；ポリビニルアルコール、ポリビニルピロリドン、カルボキシメチルセルロースナトリウム、メチルセルロース、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース等の親水性高分子；ポリソルベート類、ポリオキシエチレン硬化ヒマシ油が挙げられる。 Suitable examples of the suspending agent include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate; polyvinyl alcohol, polyvinylpyrrolidone , Hydrophilic polymers such as sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose; polysorbates, and polyoxyethylene hydrogenated castor oil.

　等張化剤の好適な例としては、塩化ナトリウム、グリセリン、Ｄ－マンニトール、Ｄ－ソルビトール、ブドウ糖が挙げられる。 Preferable examples of the isotonic agent include sodium chloride, glycerin, D-mannitol, D-sorbitol and glucose.

　緩衝剤の好適な例としては、リン酸塩、酢酸塩、炭酸塩、クエン酸塩等の緩衝液が挙げられる。
　無痛化剤の好適な例としては、ベンジルアルコールが挙げられる。 Preferable examples of the buffer include buffer solutions such as phosphate, acetate, carbonate, citrate.
A preferred example of the soothing agent is benzyl alcohol.

　防腐剤の好適な例としては、パラオキシ安息香酸エステル類、クロロブタノール、ベンジルアルコール、フェネチルアルコール、デヒドロ酢酸、ソルビン酸が挙げられる。
　抗酸化剤の好適な例としては、亜硫酸塩、アスコルビン酸塩等が挙げられる。 Preferable examples of the preservative include p-hydroxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid and sorbic acid.
Preferable examples of the antioxidant include sulfite and ascorbate.

　着色剤の好適な例としては、水溶性食用タール色素（例、食用赤色２号および３号、食用黄色４号および５号、食用青色１号および２号等の食用色素）、水不溶性レーキ色素（例、前記水溶性食用タール色素のアルミニウム塩）、天然色素（例、β－カロチン、クロロフィル、ベンガラ）が挙げられる。 Preferred examples of the colorant include water-soluble edible tar dyes (eg, edible dyes such as edible red Nos. 2 and 3, edible yellows Nos. 4 and 5, edible blue Nos. 1 and 2, etc.), water-insoluble lake dyes (Eg, the aluminum salt of the water-soluble edible tar dye) and natural dyes (eg, β-carotene, chlorophyll, bengara).

　甘味剤の好適な例としては、サッカリンナトリウム、グリチルリチン酸二カリウム、アスパルテーム、ステビアが挙げられる。 Suitable examples of sweeteners include saccharin sodium, dipotassium glycyrrhizinate, aspartame, and stevia.

　前記医薬組成物の剤形としては、例えば、錠剤（糖衣錠、フィルムコーティング錠、舌下錠、口腔内崩壊錠を含む）、カプセル剤（ソフトカプセル、マイクロカプセルを含む）、顆粒剤、散剤、トローチ剤、シロップ剤、乳剤、懸濁剤、フィルム剤（例、口腔内崩壊フィルム）等の経口剤；および注射剤（例、皮下注射剤、静脈内注射剤、筋肉内注射剤、腹腔内注射剤、点滴剤）、外用剤（例、経皮製剤、軟膏剤）、坐剤（例、直腸坐剤、膣坐剤）、ペレット、経鼻剤、経肺剤（吸入剤）、点眼剤等の非経口剤が挙げられる。
　これらはそれぞれ経口的あるいは非経口的（例、局所、直腸、静脈投与）に安全に投与できる。 Examples of the dosage form of the pharmaceutical composition include tablets (including sugar-coated tablets, film-coated tablets, sublingual tablets, orally disintegrating tablets), capsules (including soft capsules and microcapsules), granules, powders, and lozenges. Oral preparations such as syrup, emulsion, suspension, film (eg, orally disintegrating film); and injection (eg, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, Intravenous preparations, external preparations (eg, transdermal preparations, ointments), suppositories (eg, rectal suppositories, vaginal suppositories), pellets, nasal preparations, pulmonary preparations (inhalants), eye drops, etc. Oral preparations are mentioned.
These can be safely administered orally or parenterally (eg, topical, rectal, intravenous administration).

　これらの製剤は、速放性製剤または徐放性製剤等の放出制御製剤（例、徐放性マイクロカプセル）であってもよい。 These preparations may be controlled-release preparations (eg, sustained-release microcapsules) such as immediate-release preparations or sustained-release preparations.

　医薬組成物は、製剤技術分野において慣用の方法、例えば、日本薬局方に記載の方法等により製造することができる。 The pharmaceutical composition can be produced by a method commonly used in the field of pharmaceutical technology, for example, a method described in the Japanese Pharmacopoeia.

　なお、医薬組成物中の本発明化合物の含量は、剤形、本発明化合物の投与量等により異なるが、例えば、約０．１～１００重量％である。 The content of the compound of the present invention in the pharmaceutical composition varies depending on the dosage form, the dose of the compound of the present invention, etc., but is, for example, about 0.1 to 100% by weight.

　経口剤を製造する際には、必要により、味のマスキング、腸溶性あるいは持続性を目的として、コーティングを行ってもよい。 When manufacturing an oral preparation, it may be coated for the purpose of taste masking, enteric solubility or sustainability, if necessary.

　コーティングに用いられるコーティング基剤としては、例えば、糖衣基剤、水溶性フィルムコーティング基剤、腸溶性フィルムコーティング基剤、徐放性フィルムコーティング基剤が挙げられる。 Examples of the coating base used for coating include sugar coating base, water-soluble film coating base, enteric film coating base and sustained-release film coating base.

　糖衣基剤としては、白糖が用いられ、さらに、タルク、沈降炭酸カルシウム、ゼラチン、アラビアゴム、プルラン、カルナバロウ等から選ばれる１種または２種以上を併用してもよい。 As the sugar coating base, sucrose is used, and one or more selected from talc, precipitated calcium carbonate, gelatin, gum arabic, pullulan, carnauba wax and the like may be used in combination.

　水溶性フィルムコーティング基剤としては、例えば、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、メチルヒドロキシエチルセルロース等のセルロース系高分子；ポリビニルアセタールジエチルアミノアセテート、アミノアルキルメタアクリレートコポリマーＥ〔オイドラギットＥ（商品名）〕、ポリビニルピロリドン等の合成高分子；プルラン等の多糖類が挙げられる。 Examples of the water-soluble film coating base include cellulose polymers such as hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and methylhydroxyethylcellulose; polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer E [Eudragit E (trade name) ], Synthetic polymers such as polyvinylpyrrolidone; polysaccharides such as pullulan.

　腸溶性フィルムコーティング基剤としては、例えば、ヒドロキシプロピルメチルセルロース　フタレート、ヒドロキシプロピルメチルセルロース　アセテートサクシネート、カルボキシメチルエチルセルロース、酢酸フタル酸セルロース等のセルロース系高分子；メタアクリル酸コポリマーＬ〔オイドラギットＬ（商品名）〕、メタアクリル酸コポリマーＬＤ〔オイドラギットＬ－３０Ｄ５５（商品名）〕、メタアクリル酸コポリマーＳ〔オイドラギットＳ（商品名）〕等のアクリル酸系高分子；セラック等の天然物が挙げられる。 Examples of enteric film coating bases include cellulose polymers such as hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, and cellulose acetate phthalate; methacrylic acid copolymer L [Eudragit L (trade name) ] Acrylic acid polymers such as methacrylic acid copolymer LD [Eudragit L-30D55 (trade name)], methacrylic acid copolymer S [Eudragit S (trade name)]; natural products such as shellac.

　徐放性フィルムコーティング基剤としては、例えば、エチルセルロース等のセルロース系高分子；アミノアルキルメタアクリレートコポリマーＲＳ〔オイドラギットＲＳ（商品名）〕、アクリル酸エチル－メタクリル酸メチル共重合体懸濁液〔オイドラギットＮＥ（商品名）〕等のアクリル酸系高分子が挙げられる。 Examples of the sustained-release film coating base include cellulose polymers such as ethyl cellulose; aminoalkyl methacrylate copolymer RS [Eudragit RS (trade name)], ethyl acrylate-methyl methacrylate copolymer suspension [Eudragit Acrylic polymer such as NE (trade name)].

　上記したコーティング基剤は、その２種以上を適宜の割合で混合して用いてもよい。また、コーティングの際に、例えば、酸化チタン、三二酸化鉄等のような遮光剤を用いてもよい。 The above-mentioned coating bases may be used by mixing two or more of them in an appropriate ratio. Moreover, you may use light-shielding agents, such as a titanium oxide, ferric oxide, etc. in the case of coating.

　本発明化合物は、毒性（例、急性毒性、慢性毒性、遺伝毒性、生殖毒性、心毒性、癌原性）が低く、副作用も少なく、哺乳動物（例えば、ヒト、ウシ、ウマ、イヌ、ネコ、サル、マウス、ラット）に対し、各種疾患の予防または治療剤、または診断薬として用いることができる。 The compound of the present invention has low toxicity (eg, acute toxicity, chronic toxicity, genotoxicity, reproductive toxicity, cardiotoxicity, carcinogenicity), few side effects, and mammals (eg, humans, cows, horses, dogs, cats, Monkeys, mice, rats) can be used as preventive or therapeutic agents for various diseases or as diagnostic agents.

　本発明化合物は、優れたＶ１ｂ受容体拮抗作用を有しており、中枢精神疾患領域（気分障害、不安障害、統合失調症、アルツハイマー病、パーキンソン病、ハンチントン舞踏病、摂食障害、てんかん等）の予防または治療剤として有用である。 The compound of the present invention has excellent V1b receptor antagonism, and central psychiatric disorders (mood disorders, anxiety disorders, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, epilepsy, etc.) It is useful as a preventive or therapeutic agent.

　本発明化合物の投与量は、投与対象、投与ルート、対象疾患、症状等によっても異なるが、例えば、成人の骨疾患患者に経口投与する場合、通常１回量として約０．０１～１００ｍｇ／ｋｇ体重、好ましくは０．０５～３０ｍｇ／ｋｇ体重、さらに好ましくは０．１～１０ｍｇ／ｋｇ体重であり、この量を１日１回～３回投与するのが望ましい。 The dose of the compound of the present invention varies depending on the administration subject, administration route, target disease, symptom, etc. For example, when administered orally to an adult bone disease patient, it is usually about 0.01 to 100 mg / kg as a single dose. The body weight is preferably 0.05 to 30 mg / kg body weight, more preferably 0.1 to 10 mg / kg body weight, and it is desirable to administer this amount once to three times a day.

　以下に、参考例、実施例、製剤例および試験例に基づいて本発明をより詳細に説明するが、本発明は実施例により限定されるものではなく、また本発明の範囲を逸脱しない範囲で変化させてもよい。 Hereinafter, the present invention will be described in more detail based on Reference Examples, Examples, Formulation Examples, and Test Examples, but the present invention is not limited to the Examples and is within a range not departing from the scope of the present invention. It may be changed.

実施例２
（１）１－［（２－ニトロフェノキシ）アセチル］－３－ピペリジンカルボン酸エチルの合成
　３－ピペリジンカルボン酸エチル（０．７５３ｇ）をジクロロメタン（２５ｍＬ）に溶解し、ｏ－ニトロフェノキシ酢酸（１．１３ｇ）、１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（１．１１ｇ）および４－（ジメチルアミノ）ピリジン（６０ｍｇ）を添加し、室温にて終夜撹拌した。反応液を飽和重曹水、水、飽和食塩水で順次洗浄し、減圧濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝６７：３３～５０：５０）にて精製することにより、表題化合物（１．４８ｇ）を得た。
MS (ESI) m/z：337.21 [MH+], C16H20N2O6 requires 336.13 Example 2
(1) Synthesis of ethyl 1-[(2-nitrophenoxy) acetyl] -3-piperidinecarboxylate Ethyl 3-piperidinecarboxylate (0.753 g) was dissolved in dichloromethane (25 mL), and o-nitrophenoxyacetic acid (1 .13 g), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.11 g) and 4- (dimethylamino) pyridine (60 mg) were added and stirred at room temperature overnight. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 67: 33-50: 50) to give the title compound (1.48 g).
MS (ESI) m / z: 337.21 [MH + ], C 16 H 20 N 2 O 6 requires 336.13

（２）１－［（２－ニトロフェノキシ）アセチル］－３－ピペリジンカルボン酸の合成
　上記工程（１）で得られた化合物(０．７４３ｇ)をエタノール(５ｍＬ)に溶解し、水(１ｍＬ)および２Ｍ水酸化ナトリウム水溶液(１．２１ｍＬ)を添加し、室温で終夜撹拌した。反応液に１Ｍ塩酸(２．６５ｍＬ)を加えて減圧濃縮した。濃縮物に水を加えて不溶解物をろ取し、これを水で洗浄後、減圧乾燥することにより、表題化合物(０．５６９ｇ)を得た。
MS (ESI) m/z：309.11 [MH+], C14H16N2O6 requires 308.10 (2) Synthesis of 1-[(2-nitrophenoxy) acetyl] -3-piperidinecarboxylic acid The compound (0.743 g) obtained in the above step (1) was dissolved in ethanol (5 mL), and water (1 mL) was added. And 2M aqueous sodium hydroxide (1.21 mL) were added and stirred at room temperature overnight. 1M hydrochloric acid (2.65 mL) was added to the reaction mixture, and the mixture was concentrated under reduced pressure. Water was added to the concentrate, and the insoluble material was collected by filtration. This was washed with water and then dried under reduced pressure to obtain the title compound (0.569 g).
MS (ESI) m / z: 309.11 [MH + ], C 14 H 16 N 2 O 6 requires 308.10

（３）[１－((２－ニトロフェノキシ)アセチル)ピペリジン－３－イル]－[４－(３－メチルフェニル)－３－メチルピペラジン－１－イル]メタノン（実施例化合物２）の合成
　上記工程（２）で得られた化合物（３８ｍｇ）にジクロロメタン（２ｍＬ）を加え、１－ヒドロキシベンゾトリアゾール・一水和物（２３ｍｇ）、１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（２８ｍｇ）および２－メチル－１－（ｍ－トリル）ピペラジン（２８ｍｇ）を加えて２５℃で終夜撹拌した。反応液を飽和重曹水、水、飽和食塩水で順次洗浄し、減圧濃縮した。得られた残渣を逆相分取クロマトグラフィー（アセトニトリル（０．０５％ＴＦＡ）：水（０．０５％ＴＦＡ）＝１：９～９：１）にて精製した。主分画を集め、減圧濃縮することにより、表題化合物（４５ｍｇ）を得た。
1H-NMR(400MHz, MeOH-d4) δ： 7.96-7.75(m, 1H), 7.67-7.54(m, 1H), 7.46-7.03(m, 6H), 5.16-4.78(m, 2H), 4.61-4.10(m, 2H), 4.10-3.76(m, 3H), 3.76-3.35(m, 5H), 3.16-2.83(m, 2H), 2.45-2.32(m, 3H), 2.12-1.48(m, 4H), 1.12-0.89(m, 3H), MS (ESI) m/z：481.13[MH+], C26H32N4O5 requires 480.24 (3) Synthesis of [1-((2-nitrophenoxy) acetyl) piperidin-3-yl]-[4- (3-methylphenyl) -3-methylpiperazin-1-yl] methanone (Example Compound 2) Dichloromethane (2 mL) was added to the compound (38 mg) obtained in the above step (2), 1-hydroxybenzotriazole monohydrate (23 mg), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride Salt (28 mg) and 2-methyl-1- (m-tolyl) piperazine (28 mg) were added, and the mixture was stirred at 25 ° C. overnight. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and concentrated under reduced pressure. The obtained residue was purified by reverse phase preparative chromatography (acetonitrile (0.05% TFA): water (0.05% TFA) = 1: 9 to 9: 1). The main fraction was collected and concentrated under reduced pressure to obtain the title compound (45 mg).
1 H-NMR (400 MHz, MeOH-d 4 ) δ: 7.96-7.75 (m, 1H), 7.67-7.54 (m, 1H), 7.46-7.03 (m, 6H), 5.16-4.78 (m, 2H), 4.61-4.10 (m, 2H), 4.10-3.76 (m, 3H), 3.76-3.35 (m, 5H), 3.16-2.83 (m, 2H), 2.45-2.32 (m, 3H), 2.12-1.48 (m , 4H), 1.12-0.89 (m, 3H), MS (ESI) m / z: 481.13 [MH + ], C 26 H 32 N 4 O 5 requires 480.24

実施例３４
（１）［１－（ｔ－ブトキシカルボニル）ピペリジン－３（Ｓ）－イル］－［４－（３－メチルフェニル）－３－メチルピペラジン－１－イル］メタノンの合成
　（Ｓ）－Ｎ－ｔ－ブトキシカルボニルニペコチン酸（１５９ｍｇ）をジクロロメタン（３ｍＬ）に溶解し、１－ヒドロキシベンゾトリアゾール・一水和物（９７ｍｇ）、１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（１４５ｍｇ）および２－メチル－１－（ｍ－トリル）ピペラジン（１２０ｍｇ）を添加し、２５℃にて終夜撹拌した。反応液を飽和重曹水、水、飽和食塩水で順次洗浄し、減圧濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝７０：３０～３３：６７）にて精製することにより、表題化合物（２５６ｍｇ）を得た。
MS (ESI) m/z：402.24 [MH+], C23H35N3O3 requires 401.27 Example 34
(1) Synthesis of [1- (t-butoxycarbonyl) piperidin-3 (S) -yl]-[4- (3-methylphenyl) -3-methylpiperazin-1-yl] methanone (S) —N— t-Butoxycarbonylnipecotic acid (159 mg) was dissolved in dichloromethane (3 mL) to give 1-hydroxybenzotriazole monohydrate (97 mg), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (145 mg) and 2-methyl-1- (m-tolyl) piperazine (120 mg) were added and stirred at 25 ° C. overnight. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 70: 30-33: 67) to give the title compound (256 mg).
MS (ESI) m / z: 402.24 [MH + ], C 23 H 35 N 3 O 3 requires 401.27

（２）（ピペリジン－３（Ｓ）－イル）－［４－（３－メチルフェニル）－３－メチルピペラジン－１－イル］メタノン　塩酸塩の合成
　上記工程（１）で得られた化合物（２５６ｍｇ）に４Ｍ塩酸－１，４－ジオキサン溶液（２ｍＬ）を添加し、室温で１時間撹拌した。反応液を濃縮した後、ジイソプロピルエーテルを加え、固体をろ取した。これを減圧乾燥することにより、表題化合物を塩酸塩（２１２ｍｇ）として得た。
MS (ESI) m/z：302.30 [MH+], C18H27N3O requires 301.22 (2) (Piperidin-3 (S) -yl)-[4- (3-methylphenyl) -3-methylpiperazin-1-yl] methanone Synthesis of hydrochloride Compound (256 mg) obtained in the above step (1) ) Was added 4M hydrochloric acid-1,4-dioxane solution (2 mL) and stirred at room temperature for 1 hour. The reaction mixture was concentrated, diisopropyl ether was added, and the solid was collected by filtration. This was dried under reduced pressure to give the title compound as hydrochloride (212 mg).
MS (ESI) m / z: 302.30 [MH + ], C 18 H 27 N 3 O requires 301.22

（３）［１－（（Ｅ）－３－フェニルアクロイル）ピペリジン－３（Ｓ）－イル］－［４－（３－メチルフェニル）－３－メチルピペラジン－１－イル］メタノン（実施例化合物３４）の合成
　上記工程（２）で得られた化合物（４０ｍｇ）にジクロロメタン（２ｍＬ）を加え、トランス－３－フェニルアクリル酸（２４ｍｇ）、４－（ジメチルアミノ）ピリジン（２ｍｇ）、トリエチルアミン(５６μＬ)および１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（３１ｍｇ）を加えて２５℃で終夜撹拌した。反応液を飽和重曹水、水、飽和食塩水で順次洗浄し、減圧濃縮した。得られた残渣を逆相分取クロマトグラフィー（アセトニトリル（０．０５％ＴＦＡ）：水（０．０５％ＴＦＡ）＝１：９～９：１）にて精製した。主分画を集め、減圧濃縮することにより、表題化合物（実施例化合物３４）（４３ｍｇ）を得た。
1H-NMR(400MHz, MeOH-d4) δ：7.69-7.50(m, 3H), 7.50-7.30(m, 6H), 7.30-7.08(m, 2H), 4.66-4.02(m, 4H), 4.02-3.18(m, 6H), 3.18-2.83(m, 2H), 2.47-2.34(br, 3H), 2.20-1.54(m, 4H), 1.19-0.95(br, 3H), MS (ESI) m/z：432.18 [MH+], C27H33N3O2requires 431.26 (3) [1-((E) -3-Phenylacryloyl) piperidin-3 (S) -yl]-[4- (3-methylphenyl) -3-methylpiperazin-1-yl] methanone (Examples) Synthesis of Compound 34) Dichloromethane (2 mL) was added to the compound (40 mg) obtained in the above step (2), and trans-3-phenylacrylic acid (24 mg), 4- (dimethylamino) pyridine (2 mg), triethylamine ( 56 μL) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (31 mg) were added and stirred at 25 ° C. overnight. The reaction mixture was washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and concentrated under reduced pressure. The obtained residue was purified by reverse phase preparative chromatography (acetonitrile (0.05% TFA): water (0.05% TFA) = 1: 9 to 9: 1). The main fraction was collected and concentrated under reduced pressure to obtain the title compound (Example compound 34) (43 mg).
1 H-NMR (400 MHz, MeOH-d 4 ) δ: 7.69-7.50 (m, 3H), 7.50-7.30 (m, 6H), 7.30-7.08 (m, 2H), 4.66-4.02 (m, 4H), 4.02-3.18 (m, 6H), 3.18-2.83 (m, 2H), 2.47-2.34 (br, 3H), 2.20-1.54 (m, 4H), 1.19-0.95 (br, 3H), MS (ESI) m / z: 432.18 [MH + ], C 27 H 33 N 3 O 2 requires 431.26

　製造ルート（１）または（２）に準じて、それぞれ対応する原料を使用して、以下の化合物を製造した。なお、対応する原料は市販品を使用するか、あるいは自体公知の方法に準じて製造した。化合物の構造式および物理化学的データを表１に示す。 According to the production route (1) or (2), the following compounds were produced using the corresponding raw materials. In addition, the corresponding raw material used a commercial item, or manufactured according to a method known per se. The structural formulas and physicochemical data of the compounds are shown in Table 1.

Figure JPOXMLDOC01-appb-T000030
Figure JPOXMLDOC01-appb-T000030

Figure JPOXMLDOC01-appb-T000031
Figure JPOXMLDOC01-appb-T000031

Figure JPOXMLDOC01-appb-T000032
Figure JPOXMLDOC01-appb-T000032

Figure JPOXMLDOC01-appb-T000033
Figure JPOXMLDOC01-appb-T000033

Figure JPOXMLDOC01-appb-T000034
Figure JPOXMLDOC01-appb-T000034

Figure JPOXMLDOC01-appb-T000035
Figure JPOXMLDOC01-appb-T000035

Figure JPOXMLDOC01-appb-T000036
Figure JPOXMLDOC01-appb-T000036

Figure JPOXMLDOC01-appb-T000037
Figure JPOXMLDOC01-appb-T000037

Figure JPOXMLDOC01-appb-T000038
Figure JPOXMLDOC01-appb-T000038

Figure JPOXMLDOC01-appb-T000039
Figure JPOXMLDOC01-appb-T000039

Figure JPOXMLDOC01-appb-T000040
Figure JPOXMLDOC01-appb-T000040

Figure JPOXMLDOC01-appb-T000041
Figure JPOXMLDOC01-appb-T000041

Figure JPOXMLDOC01-appb-T000042
Figure JPOXMLDOC01-appb-T000042

Figure JPOXMLDOC01-appb-T000043
Figure JPOXMLDOC01-appb-T000043

Figure JPOXMLDOC01-appb-T000044
Figure JPOXMLDOC01-appb-T000044

Figure JPOXMLDOC01-appb-T000045
Figure JPOXMLDOC01-appb-T000045

製剤例１（カプセルの製造）
　１）実施例２の化合物　　　　　　　　　　　　　　　　　　３０　ｍｇ
　２）微粉末セルロース　　　　　　　　　　　　　　　　　　１０　ｍｇ
　３）乳糖　　　　　　　　　　　　　　　　　　　　　　　　１９　ｍｇ
　４）ステアリン酸マグネシウム　　　　　　　　　　　　　　　１　ｍｇ
　　　　　　　　　　　　　　　　　　　　　　　　　　　計　６０　ｍｇ
　１）、２）、３）および４）を混合して、ゼラチンカプセルに充填する。 Formulation Example 1 (Manufacture of capsules)
1) Compound of Example 2 30 mg
2) Fine powder cellulose 10 mg
3) Lactose 19 mg
4) Magnesium stearate 1 mg
60 mg total
1), 2), 3) and 4) are mixed and filled into gelatin capsules.

製剤例２（錠剤の製造）
　１）実施例３４の化合物　　　　　　　　　　　　　　　　　３０　ｇ
　２）乳糖　　　　　　　　　　　　　　　　　　　　　　　　５０　ｇ
　３）トウモロコシデンプン　　　　　　　　　　　　　　　　１５　ｇ
　４）カルボキシメチルセルロースカルシウム　　　　　　　　４４　ｇ
　５）ステアリン酸マグネシウム　　　　　　　　　　　　　　　１　ｇ
　　　　　　　　　　　　　　　　　　　１０００錠　　計　１４０　ｇ
　１）、２）、３）の全量および３０ｇの４）を水で練合し、真空乾燥後、整粒を行う。この整粒末に１４ｇの４）および１ｇの５）を混合し、打錠機により打錠する。このようにして、１錠あたり実施例３４の化合物３０ｍｇを含有する錠剤１０００錠を得る。 Formulation Example 2 (Manufacture of tablets)
1) Compound of Example 34 30 g
2) Lactose 50 g
3) Corn starch 15 g
4) Carboxymethylcellulose calcium 44 g
5) Magnesium stearate 1 g
1000 tablets total 140 g
The total amount of 1), 2) and 3) and 30 g of 4) are kneaded with water, and after vacuum drying, the particles are sized. 14 g of 4) and 1 g of 5) are mixed with the sized powder, and tableted with a tableting machine. In this way, 1000 tablets containing 30 mg of the compound of Example 34 per tablet are obtained.

試験例１：V1b受容体拮抗作用の測定方法
　ヒトV1b受容体安定発現HEK293細胞は、ダルベッコ変法イーグル培地(4500mg/L glucose、10%FBS、ペニシリン／ストレプトマイシン含む)にて培養し、試験の前日に96ウェルプレート（黒色透明底、ハーフエリア）のウェル毎に30000細胞を播種した。測定１時間前に培養液を除いて緩衝液（1xHBSS、20mM HEPES pH7.4）に置き換え、ローディング色素溶液（FLIPR Calcium5 assay kit）を添加して37℃のCO２インキュベータ内で静置した。測定１０分前に各被検化合物を含む溶液を添加し、１０分間37℃で静置した後、測定機器FlexStation（モレキュラーデバイス社）を用いてAVP（0.1nM）の刺激による細胞内カルシウム濃度の反応を測定した。蛍光強度の検出により計測値の経時変化データを取得し、刺激前の定常状態の値と反応ピークの値の差分を反応強度とした。化合物を添加しない条件でのAVP刺激による反応を100%として、各被検化合物による50%阻害濃度（IC50）を算出した。本発明化合物のV1b受容体拮抗作用における代表的な化合物のIC50値を表２に示す。 Test Example 1: Method for Measuring V1b Receptor Antagonism HEK293 cells stably expressing human V1b receptor were cultured in Dulbecco's modified Eagle medium (4500 mg / L glucose, 10% FBS, containing penicillin / streptomycin) and the day before the test. 30000 cells were seeded per well of a 96 well plate (black transparent bottom, half area). One hour before the measurement, the culture solution was removed and replaced with a buffer solution (1 × HBSS, 20 mM HEPES pH 7.4), a loading dye solution (FLIPR Calcium 5 assay kit) was added, and the mixture was allowed to stand in a 37 ° C. CO 2 incubator. 10 minutes before the measurement, a solution containing each test compound was added and allowed to stand at 37 ° C. for 10 minutes, and then the intracellular calcium concentration by stimulation of AVP (0.1 nM) was measured using the measuring instrument FlexStation (Molecular Device). The reaction was measured. The time-dependent change data of the measured value was acquired by detecting the fluorescence intensity, and the difference between the steady state value before stimulation and the reaction peak value was defined as the reaction intensity. The 50% inhibitory concentration (IC 50 ) of each test compound was calculated with the reaction due to AVP stimulation under the condition where no compound was added as 100%. Table 2 shows IC 50 values of typical compounds in the V1b receptor antagonism of the compounds of the present invention.

Figure JPOXMLDOC01-appb-T000046
Figure JPOXMLDOC01-appb-T000046

　本発明化合物は、アルギニン－バソプレシン１ｂ受容体拮抗作用を有することより、中枢精神疾患領域（気分障害、不安障害、統合失調症、アルツハイマー病、パーキンソン病、ハンチントン舞踏病、摂食障害、てんかん等）の疾患における予防または治療剤として有用である。 Since the compound of the present invention has an arginine-vasopressin 1b receptor antagonistic action, it has central psychiatric disorders (mood disorders, anxiety disorders, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, epilepsy, etc.) It is useful as a preventive or therapeutic agent for various diseases.

　本出願は、日本国で２０１２年８月９日に出願された特願２０１２－１７７５７２を基礎としており、その内容は本明細書にすべて包含されるものである。 This application is based on Japanese Patent Application No. 2012-177572 filed on August 9, 2012 in Japan, the contents of which are incorporated in full herein.

Claims (23)

　一般式（Ｉ）：
Figure JPOXMLDOC01-appb-C000001
 （式中、
環Ａは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１は、
(1) －ＣＨ＝ＣＨ－Ｒｘ（式中、Ｒｘは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよい芳香族複素環基を示す。）で表される基；
(2) －ＣＨ２－Ｏ－Ｒｙ（式中、Ｒｙは、置換されていてもよいＣ６－１４アリール基を示す。）で表される基；
(3) －（ＣＨ２）ｎ－Ｒｚ（式中、Ｒｚは、置換されていてもよいＣ６－１４アリール基を示し、ｎは、１ないし５の整数を示す。）で表される基；
(4) 置換されていてもよいＣ６－１４アリール基；または
(5) 置換されていてもよい縮合環基
を示し；
Ｒ２、Ｒ３、Ｒ４およびＲ５は、それぞれ独立して、水素原子または置換基を示し；
Ｒ６は、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基を示す。）
で表される化合物またはその塩を含有する、アルギニン－バソプレシン１ｂ受容体拮抗剤。 Formula (I):
Figure JPOXMLDOC01-appb-C000001
 (Where
Ring A represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1 is
(1) —CH═CH—R x (wherein R x represents an optionally substituted C 6-14 aryl group or an optionally substituted aromatic heterocyclic group). Group;
(2) (wherein, R y represents an optionally substituted C 6-14 aryl group.) -CH 2 -O-R y group represented by;
(3) - (CH 2) n -R z ( wherein, R z is substituted indicates which may C 6-14 aryl group, n is 1 to an integer of 5.) Is represented by Group;
(4) an optionally substituted C 6-14 aryl group; or
(5) represents an optionally substituted fused ring group;
R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom or a substituent;
R 6 is optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show. )
An arginine-vasopressin 1b receptor antagonist comprising a compound represented by the formula: 　一般式（Ｉａ）：
Figure JPOXMLDOC01-appb-C000002
 （式中、
環Ａａは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ａは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよい芳香族複素環基を示し；
Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの少なくとも１つは置換基を示し、かつ残りは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ａは、置換されていてもよいＣ６－１４アリール基、または置換されていてもよいＣ７－１６アラルキル基を示す。）
で表される化合物またはその塩。 Formula (Ia):
Figure JPOXMLDOC01-appb-C000002
 (Where
Ring Aa represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1a represents an optionally substituted C 6-14 aryl group, or an optionally substituted aromatic heterocyclic group;
At least one of R 2a , R 3a , R 4a and R 5a represents a substituent, and the rest each independently represents a hydrogen atom or a substituent;
R 6a represents an optionally substituted C 6-14 aryl group or an optionally substituted C 7-16 aralkyl group. )
Or a salt thereof. 　Ｒ１ａが、ニトロ基でそれぞれ置換されていてもよい、Ｃ６－１０アリール基または５または６員の単環式芳香族複素環基である、請求項２記載の化合物またはその塩。 The compound or a salt thereof according to claim 2, wherein R 1a is a C 6-10 aryl group or a 5- or 6-membered monocyclic aromatic heterocyclic group, each optionally substituted with a nitro group. 　Ｒ２ａ、Ｒ３ａ、Ｒ４ａおよびＲ５ａの１つがＣ１－６アルキル基であり、かつ残り３つが水素原子である、請求項２記載の化合物またはその塩。 The compound or a salt thereof according to claim 2, wherein one of R 2a , R 3a , R 4a and R 5a is a C 1-6 alkyl group, and the remaining three are hydrogen atoms. 　Ｒ６ａが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基、またはＣ７－１３アラルキル基である、請求項２記載の化合物またはその塩。 The compound or a salt thereof according to claim 2, wherein R 6a is a C 6-10 aryl group optionally substituted with a C 1-6 alkyl group, or a C 7-13 aralkyl group. 　環Ａａが、Ｃ１－６アルキル基でそれぞれ置換されていてもよい、ピロリジン環、ピペリジン環またはアゼパン環である、請求項２記載の化合物またはその塩。 The compound or a salt thereof according to claim 2, wherein ring Aa is a pyrrolidine ring, piperidine ring or azepane ring each optionally substituted with a C 1-6 alkyl group. 　一般式（Ｉｂ）：
Figure JPOXMLDOC01-appb-C000003
 （式中、
環Ａｂは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ｂは、
(1) ニトロ基およびＣ１－６アルコキシ基で置換されたＣ６－１４アリール基、
(2) 置換されていてもよいベンゾフリル、または
(3) 置換されていてもよいインダニル
を示し；
Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ｂは、置換されていてもよいＣ６－１４アリール基を示す。）
で表される化合物またはその塩。 Formula (Ib):
Figure JPOXMLDOC01-appb-C000003
 (Where
Ring Ab represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1b is
(1) a C 6-14 aryl group substituted with a nitro group and a C 1-6 alkoxy group,
(2) optionally substituted benzofuryl, or
(3) represents an optionally substituted indanyl;
R 2b , R 3b , R 4b and R 5b each independently represent a hydrogen atom or a substituent;
R 6b represents an optionally substituted C 6-14 aryl group. )
Or a salt thereof. 　Ｒ１ｂが、
(1) １個のニトロ基と１または２個のＣ１－６アルコキシ基で置換されたＣ６－１０アリール基、
(2) ベンゾフリル、または
(3) インダニル
である、請求項７記載の化合物またはその塩。 R 1b is
(1) a C 6-10 aryl group substituted with one nitro group and one or two C 1-6 alkoxy groups,
(2) benzofuryl, or
(3) The compound or salt thereof according to claim 7, which is indanyl. 　Ｒ２ｂ、Ｒ３ｂ、Ｒ４ｂおよびＲ５ｂの少なくとも１つがＣ１－６アルキル基であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基である、請求項７記載の化合物またはその塩。 8. At least one of R 2b , R 3b , R 4b and R 5b is a C 1-6 alkyl group, and the rest are each independently a hydrogen atom or a C 1-6 alkyl group. Compound or salt thereof. 　Ｒ６ｂが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基である、請求項７記載の化合物またはその塩。 The compound or a salt thereof according to claim 7, wherein R 6b is a C 6-10 aryl group optionally substituted with a C 1-6 alkyl group. 　環Ａｂが、Ｃ１－６アルキル基で置換されていてもよいピペリジン環である、請求項７記載の化合物またはその塩。 The compound or a salt thereof according to claim 7, wherein Ring Ab is a piperidine ring optionally substituted with a C 1-6 alkyl group. 　一般式（Ｉｃ）：
Figure JPOXMLDOC01-appb-C000004
 （式中、
環Ａｃは、５ないし７員含窒素飽和複素環を示し；
Ｒ１ｃは、置換されていてもよいＣ６－１４アリール基を示し；
Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ｃは、置換されていてもよいＣ６－１４アリール基、置換されていてもよいＣ７－１６アラルキル基、または置換されていてもよいＣ６－１０アリール－Ｃ２－６アルケニル基を示す。）
で表される化合物またはその塩。 Formula (Ic):
Figure JPOXMLDOC01-appb-C000004
 (Where
Ring Ac represents a 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1c represents an optionally substituted C 6-14 aryl group;
R 2c , R 3c , R 4c and R 5c each independently represent a hydrogen atom or a substituent;
R 6c is an optionally substituted C 6-14 aryl group, an optionally substituted C 7-16 aralkyl group optionally or optionally substituted C 6-10 aryl -C 2-6 alkenyl group, Show. )
Or a salt thereof. 　Ｒ１ｃが、ニトロ基で置換されていてもよいＣ６－１０アリール基である、請求項１２記載の化合物またはその塩。 The compound or a salt thereof according to claim 12, wherein R 1c is a C 6-10 aryl group which may be substituted with a nitro group. 　Ｒ２ｃ、Ｒ３ｃ、Ｒ４ｃおよびＲ５ｃの少なくとも１つがＣ１－６アルキル基であり、かつ残りが、それぞれ独立して、水素原子またはＣ１－６アルキル基である、請求項１２記載の化合物またはその塩。 13. At least one of R 2c , R 3c , R 4c and R 5c is a C 1-6 alkyl group, and the rest are each independently a hydrogen atom or a C 1-6 alkyl group. Compound or salt thereof. 　Ｒ６ｃが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基、Ｃ１－６アルキル基で置換されていてもよいＣ７－１６アラルキル基、またはＣ６－１０アリール－Ｃ２－６アルケニル基である、請求項１２記載の化合物またはその塩。 R 6c is, C 1-6 alkyl optionally substituted with C 6-10 aryl group, C 1-6 alkyl an optionally substituted C 7-16 aralkyl group or a group C 6-10 aryl, 13. The compound or a salt thereof according to claim 12, which is a —C 2-6 alkenyl group. 　環Ａｃが、ピペリジン環である、請求項１２記載の化合物またはその塩。 The compound or a salt thereof according to claim 12, wherein Ring Ac is a piperidine ring. 　一般式（Ｉｄ）：
Figure JPOXMLDOC01-appb-C000005
 （式中、
環Ａｄは、置換されていてもよい５ないし７員含窒素飽和複素環を示し；
Ｒ１ｄは、置換されていてもよいＣ６－１４アリール基を示し；
Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの少なくとも１つは置換基を示し、かつ残りは、それぞれ独立して、水素原子または置換基を示し；
Ｒ６ｄは、置換されていてもよいＣ６－１４アリール基を示し；
ｎｄは、１ないし５の整数を示す。）
で表される化合物またはその塩。 Formula (Id):
Figure JPOXMLDOC01-appb-C000005
 (Where
Ring Ad represents an optionally substituted 5- to 7-membered nitrogen-containing saturated heterocyclic ring;
R 1d represents an optionally substituted C 6-14 aryl group;
At least one of R 2d , R 3d , R 4d and R 5d represents a substituent, and the rest each independently represents a hydrogen atom or a substituent;
R 6d represents an optionally substituted C 6-14 aryl group;
n d represents an integer of 1 to 5. )
Or a salt thereof. 　Ｒ２ｄ、Ｒ３ｄ、Ｒ４ｄおよびＲ５ｄの１つがＣ１－６アルキル基であり、かつ残り３つが水素原子である、請求項１７記載の化合物またはその塩。 The compound or a salt thereof according to claim 17, wherein one of R 2d , R 3d , R 4d and R 5d is a C 1-6 alkyl group, and the remaining three are hydrogen atoms. 　Ｒ６ｄが、Ｃ１－６アルキル基で置換されていてもよいＣ６－１０アリール基である、請求項１７記載の化合物またはその塩。 The compound or a salt thereof according to claim 17, wherein R 6d is a C 6-10 aryl group which may be substituted with a C 1-6 alkyl group. 　環Ａｄが、ピペリジン環である、請求項１７記載の化合物またはその塩。 The compound or a salt thereof according to claim 17, wherein Ring Ad is a piperidine ring. 　ｎｄが、１ないし３の整数である、請求項１７記載の化合物またはその塩。 The compound or a salt thereof according to claim 17, wherein n d is an integer of 1 to 3. 　請求項２ないし２１のいずれかに記載の化合物またはその塩、および医薬上許容される担体を含有する医薬組成物。 A pharmaceutical composition comprising the compound according to any one of claims 2 to 21 or a salt thereof, and a pharmaceutically acceptable carrier. 　請求項１ないし２１のいずれかに記載の化合物またはその塩を含有する、気分障害、不安障害、統合失調症、アルツハイマー病、パーキンソン病、ハンチントン舞踏病、摂食障害またはてんかんの予防または治療剤。 A preventive or therapeutic agent for mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder or epilepsy, comprising the compound according to any one of claims 1 to 21 or a salt thereof.
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