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WO2001007401A1 - Composes tricycliques et compositions medicamenteuses les contenant - Google Patents

Composes tricycliques et compositions medicamenteuses les contenant Download PDF

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Publication number
WO2001007401A1
WO2001007401A1 PCT/JP2000/004726 JP0004726W WO0107401A1 WO 2001007401 A1 WO2001007401 A1 WO 2001007401A1 JP 0004726 W JP0004726 W JP 0004726W WO 0107401 A1 WO0107401 A1 WO 0107401A1
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WIPO (PCT)
Prior art keywords
substituent
ring
lower alkyl
rab
optionally
Prior art date
Application number
PCT/JP2000/004726
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English (en)
Japanese (ja)
Inventor
Norihiko Tanimoto
Masanao Inagaki
Original Assignee
Shionogi & Co., Ltd.
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Priority to AU60160/00A priority Critical patent/AU6016000A/en
Publication of WO2001007401A1 publication Critical patent/WO2001007401A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • 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
    • A61K31/075—Ethers or acetals
    • 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
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
    • 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
    • A61K31/13—Amines
    • A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • 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
    • 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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
    • C07C251/58—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • C07D213/77—Hydrazine radicals

Definitions

  • Tricyclic compounds and pharmaceutical compositions art "The present invention containing it new tricyclic compounds, immunosuppressive agent containing the same, and an antiallergic agent Contact and I g E antibody production inhibitor BACKGROUND
  • immunosuppressants such as azathioprine, corticoid, cyclosporin A and evening clolimus have been developed and put into practical use, and are used for the prevention and treatment of rejection to organ or tissue transplantation and graft-versus-host reaction caused by bone marrow transplantation. ing. However, they are not always satisfactory in terms of efficacy and side effects.
  • allergic diseases such as atopic dermatitis, allergic rhinitis, bronchial asthma, and allergic conjunctivitis have been increasing worldwide in recent years and have become a major problem.
  • Conventional antiallergic agents include inhibitors of the release of chemical mediators from mast cells, inhibitors of the receptor for released chemical mediators, and inhibitors of allergic inflammatory reactions, all of which are symptomatic treatments.
  • it is not a cure for fundamental allergic diseases.
  • JP-A-Heisei 1106-1686 JP-A-Heisei 1106-871, JP-A-Heisei 2-83346, JP-A-Heisei 9-148760, and JP-A-Heisei 9-131106 3, WO8Z07992, etc.
  • compounds having insecticidal and acaricidal activity are disclosed in JP-A-8-193607, and compounds having an activity of treating cardiovascular diseases and psychosis are EP0600.
  • An object of the present invention is to provide a compound having an excellent immunosuppressive action and / or antiallergic action, and a pharmaceutical composition containing the same.
  • the present invention is a.
  • ring A, ring B and ring C each independently may have an aromatic carbon ring which may have a substituent or may have a substituent, and may be fused to a benzene ring.
  • W 3 represents a bond.
  • X is —0—, one CH 2 —, —NR 1 — (where R 1 is hydrogen, lower alkyl, lower alkenyl or lower alkyl carbonyl which may have a substituent) or one S (0) p — (Where p is an integer between 0 and 2)
  • X is one 0— or one NH—
  • Y is hydrogen, lower alkyl optionally having substituent (s), lower alkoxy optionally having substituent (s), lower alkenyl optionally having substituent (s), optionally having substituent (s) Lower alkynyl, optionally substituted acyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl
  • a sulfamoyl which may have a substituent, an amino which may have a substituent, a aryl which may have a substituent or a 5- or 6-member which may have a substituent Is a heterocyclic group of
  • Y may be halogen
  • Y may be lower alkylsulfonyl which may have a substituent or arylsulfonyl which may have a substituent.
  • R 2 is hydrogen or lower alkyl
  • one CO— one NH C HR 3 —
  • one CHR 3 NH— R 3 is hydrogen or hydroxy
  • RC and R d are each independently hydrogen, lower alkyl which may have a substituent, lower alkenyl which may have a substituent, lower alkynyl which may have a substituent, Lower alkoxy optionally having, lower alkylthio optionally having a substituent, lower alkenyloxy optionally having a substituent, lower alkynyloxy optionally having a substituent, substitution
  • R e is each independently hydrogen, lower alkyl, lower alkoxy or amino;
  • R f is each independently hydrogen; Lower alkyl , Lower alkoxy or amino
  • n is an integer from 0 to 2
  • r is an integer from 2 to 6.
  • a ring A, B ring and C ring are each independently base may have a substituent Nze down ring or hetero ring optionally having a substituent to the even or 6-membered, V 1 And V 2 are both a single bond and n is 0, the compound according to [1],
  • Ring B has a benzene ring which may have a substituent, a pyridine ring which may have a substituent, a pyrimidine ring which may have a substituent, and a group which has a substituent
  • the ring C is a benzene ring which may have a substituent or may have a substituent, and is a 6-membered hetero ring containing one or two hetero atoms,
  • Y is hydrogen, lower alkyl optionally having substituent (s), lower alkenyl optionally having substituent (s), lower alkynyl optionally having substituent (s), optionally having substituent (s) Cycloalkyl, cycloalkenyl optionally having substituent (s), or amino which may have substituent (s),
  • R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 each independently have hydrogen, halogen, optionally protected hydroxy, and a substituent.
  • a compound represented by [8] The compound according to [7], wherein R 4 and R 5 are each independently hydrogen, halogen, hydroxy or lower alkoxy.
  • R 10 may be a protected hydroxy, an optionally substituted lower alkyl, an optionally substituted lower alkoxy or a substituted A compound according to [7], which is a good lower alkoxycarbonyl;
  • Ring C is a benzene ring which may have a substituent, a pyridine ring which may have a substituent, a pyrimidine ring which may have a substituent, and which has a substituent
  • n 0 or 1
  • X is -0-
  • R c and R d are each independent Hydrogen, alkyl having 1 to 6 carbons, alkenyl having 2 to 6 carbons, alkoxy or phenyl having 1 to 6 carbons, or 5 to 5 carbons together with the carbon atoms bonded together.
  • n 0, X and are -NH-, and Ra and Rb are each independently hydrogen, lower alkyl, lower alkenyl or lower alkoxycarbonyl, or (CR e R f) r— wherein R e is each independently hydrogen, lower alkyl, lower alkoxy or amino; and R f is each independently hydrogen, lower alkyl, lower alkoxy or amino.
  • R is 4 or 5 A compound according to any one of [1], [2] or [7],
  • Ring C is a benzene ring optionally substituted with halogen, lower alkyl or lower alkoxy or a pyridine ring optionally substituted with halogen, lower alkyl or lower alkoxy,
  • X and X ' are each independently 10- or 1NH-,
  • Y is hydrogen, lower alkyl, arylalkyl, lower alkenyl or cycloalkyl
  • R 4 and R 5 are each independently hydrogen or halogen
  • R 6 and R 7 are both hydrogen
  • R 8 is hydrogen or lower alkyl
  • R 9 is hydroxy, lower alkyl or lower alkoxy
  • R 10 is hydroxy, lower alkyl, lower alkoxy or lower alkoxycarbonyl
  • R 11 is hydrogen, hydroxy or lower alkyl
  • R c and R d are each independently hydrogen, lower alkyl, lower alkenyl, lower alkoxy or phenyl, or together with the carbon atom to which they are attached, form a cycloalkylidene having 5 or 6 carbon atoms;
  • R e is each independently hydrogen, lower alkyl, lower alkoxy or amino;
  • R f is each independently hydrogen, lower alkyl, lower alkoxy or amino;
  • the compound according to any one of [1] to [22] Provided is a pharmaceutical composition containing a prodrug, a pharmaceutically acceptable salt thereof, or a solvate thereof, specifically, an immunosuppressant, an anti-allergic agent or an IgE antibody production inhibitor.
  • halogen includes fluorine, chlorine, bromine and iodine. Particularly, fluorine and chlorine are preferred.
  • any commonly used protecting group can be suitably used.
  • “Lower alkyl” means a straight or branched alkyl having 1 to 10 carbon atoms, preferably 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms, and most preferably 1 to 3 carbon atoms. And includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, hexyl, isohexyl, n-heptyl, iso- Butyl, n-octyl, isooctyl, n-nonyl and n-decyl.
  • Examples of the substituent of the “lower alkyl optionally having substituent (s)” include halogen; hydroxy which may be protected; lower alkoxy which may be substituted by lower alkoxy; acyl; acyloxy; carboxy Lower alkoxycarbonyl; mercapto; lower alkylthio; hydroxy, lower alkyl or substituted Amino optionally substituted with an optionally substituted group; hydroxy, lower alkoxy, carboxy lower alkoxy, aryl lower alkoxy or substituted with a 5- or 6-membered heterocyclic group.
  • Hydrazono optionally substituted by carbamoyl or lower alkoxycarbonyl; sorbamoyl optionally substituted by lower alkyl or amino; thiocarbamoyl optionally substituted by lower alkyl A cycloalkyl optionally substituted with lower alkyl or lower alkoxy; a cycloalkenyl optionally substituted with lower alkyl; cyano; one or more substituted with hydroxy, lower alkyl, carboxy, lower alkoxycarbonyl or lower alkoxy; Phenyl; lower al A 5- or 6-membered heterocyclic group which may be substituted with a benzene ring which may be substituted with a benzene ring.One or more arbitrary positions may be substituted with these substituents.
  • a halogen a hydroxy; an acyl; a carboxy; a lower alkoxycarbonyl; a phenyl; a lower alkylphenyl; a lower alkoxyphenyl; or a lower alkyl which may be substituted with pyridyl or the like.
  • a halogen a hydroxy; an acyl; a carboxy; a lower alkoxycarbonyl; a phenyl; a lower alkylphenyl; a lower alkoxyphenyl; or a lower alkyl which may be substituted with pyridyl or the like.
  • Lower alkoxy optionally having substituent (s) "lower alkoxycarbonyl optionally having substituent (s)”, “lower alkyl sulfonyl optionally having substituent (s)” and "substituted
  • the lower alkylthio which may be substituted is halogen; hydroxy which may be protected; lower alkoxy which may be substituted by acyloxy; acyl; which may be substituted by hydroxy or carboxy Good acyloxy; carboxy; lower alkoxycarbonyl; lower Alkylthio; amino optionally substituted with lower alkyl; phenyl optionally substituted with lower alkyl or lower alkoxy; heterocyclic group; heterocyclic carbonyloxy; And it may be substituted by the following substituents. Preferably it is unsubstituted lower alkoxy.
  • “Lower alkenyl” means 2 carbon atoms having one or more double bonds at any position.
  • It includes straight-chain or branched alkenyl having up to 10 carbon atoms, preferably 2 to 8 carbon atoms, and more preferably 3 to 6 carbon atoms.
  • penjenyl hexenyl
  • isohexenyl, hexahexenyl Heptenyl, octenyl, nonenyl, decenyl and the like.
  • lower alkenyl optionally having substituent (s) is the same as the substituent of "lower alkoxy optionally having substituent (s)" described above, and one or more arbitrary positions may be any of these substituents. May be substituted. Particularly, those which are halogen-substituted or unsubstituted are preferred.
  • lower alkenyl part of “lower alkenyloxy”, “lower alkenyloxycarbonyl” and “lower alkenylamino” is the same as the above “lower alkenyl”.
  • lower alkiel includes straight-chain or branched alkynyl having 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms, and more preferably 3 to 6 carbon atoms. Is ethynyl, propynyl (2-propynyl etc.), butynyl (2-petinyl Pentyl, hexynyl, heptynyl, octynyl, nonyl, decynyl and the like. These have a triple bond at one or more arbitrary positions, and may further have a double bond.
  • the substituent of the “lower alkynyl optionally having a substituent” is the same as the substituent of the “lower alkoxy optionally having a substituent” described above. One or more arbitrary positions may be substituted with these substituents.
  • lower alkynyl moiety of "lower alkynyloxy" and the substituent of “lower alkynyloxy optionally having substituent (s)" are the above-mentioned “lower alkynyl” and “lower alkynyl optionally having substituent (s)”. It is the same as "Kishi”.
  • “Aciyl” refers to straight or branched alkylcarbonyl or C3-10, more preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and more preferably 1 to 4 carbon atoms. Or a straight-chain or branched alkenylcarbonyl having 3 to 6 carbon atoms, most preferably a cycloalkylcarbonyl and an arylcarbonyl having 4 to 9 carbon atoms, preferably 4 to 7 carbon atoms. Include.
  • Arroyl means arylcarbonyl and aromatic heterocyclic carbonyl.
  • the aromatic hetero ring includes, for example, a pyrrole ring, an imidazole ring, a pyrazole ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a triazole ring, a triazine ring, an isoxazole ring, and an oxazolone.
  • arylcarbonyl is It may have lower alkyl as a substituent.
  • acyl part of “Asiloxy” is the same as the above “Asil”.
  • substituent of “optionally substituted alkoxy” is the same as the above “optionally substituted acyl”, and one or more arbitrary positions are substituted with these substituents. Is also good.
  • lower alkylcarbonyl includes aliphatic acetyls having 2 to 4 carbon atoms, and includes acetyl, propionyl, butyryl, and isobutyryl. In particular, acetyl is preferred.
  • Cycloalkyl is a carbocyclic group having 3 to 6 carbon atoms, and includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
  • substituents include lower alkyl, halogen, hydroxy which may be protected, carboxy, lower alkoxycarbonyl, lower alkoxy, lower alkylenedioxy. And an amino, aryl or 5- or 6-membered heterocyclic group which may be substituted with lower alkoxy, and one or more arbitrary positions may be substituted. Preferably it is unsubstituted cycloalkyl.
  • Cycloalkenyl includes those having one or more double bonds at any position in the above cycloalkyl ring, and specifically includes cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentenyl, Hexenyl and cyclohexagenyl and the like.
  • the substituent of the “cycloalkenyl optionally having substituent (s)” is the same as the substituent of the above “cycloalkyl”. One or more arbitrary positions may be substituted with these substituents.
  • Cycloalkylidene includes a divalent carbocyclic group having 3 to 6 carbon atoms, and specifically includes cyclopropylidene, cyclobutylidene, cyclopentylidene and cyclohexylidene. "Cycloalkyl optionally having substituent (s) The substituents of “redene” are the same as the substituents of the above “cycloalkyl”, and one or more arbitrary positions may be substituted with these substituents. Preferably it is unsubstituted cycloalkylidene.
  • substituent of “amino which may have a substituent” examples include lower alkyl which may have a substituent [where the substituent means lower alkoxy, cycloalkyl, or a substituent.
  • Optionally substituted amino (substituent is aryloxy which may be substituted by acyloxy lower alkoxy), aryl which may have substituent (substituent is lower alkyl, lower alkoxy, carboxy, lower alkoxy) Lower alkenyl; lower alkynyl; cycloalkyl; lower alkyl, carboxy, acyl, aryl which may be substituted with lower alkoxycarbonyl, which may be substituted with lower alkyl) Sulfamoyl; lower alkoxycarbonyl optionally having substituent (s) (wherein, the substituent is halogen, acylo) Shi, human Dorokishi substituted Ashiruokishi, carboxy-substituted ⁇ shea Ruokishi or heterocyclic
  • substituted amino are lower alkylamino, lower alkenylamino, cycloalkylamino, phenylamino and lower alkoxycarbonylamino. One or more arbitrary positions may be substituted with these substituents.
  • rubamoyl includes sorbamoyl and the like which may be substituted with one or more groups selected from lower alkyl, lower alkenyl, lower alkynyl and the like.
  • the “optionally substituted sulfamoyl” includes sulfamoyl and the like which may be substituted with one or more groups selected from lower alkyl, lower alkenyl, lower alkynyl and the like.
  • the “aromatic carbocycle” is a monocyclic or polycyclic aromatic carbocycle, and includes a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring and the like. Especially Nsen ring is preferred. Further, the “aromatic carbocycle” may be condensed with another carbocycle, and includes an indane ring, an indene ring and a dihydronaphthalene ring.
  • Aryl is a group obtained by removing one hydrogen from a monocyclic or polycyclic aromatic carbocyclic ring, and includes phenyl, naphthyl, anthryl, phenanthryl and the like. Particularly preferred is phenyl. Further, “aryl” may be condensed with another carbocycle, or may have a bond on the condensed carbocycle. Examples include indanyl, indenyl, dihydronaphthyl and the like.
  • substituents of the “optionally substituted aromatic carbocycle”, the “optionally substituted aryl” and the “optionally substituted benzene ring” include: Halogen; optionally protected hydroxy; lower alkyl optionally substituted with halogen or carboxy; lower optionally substituted with halogen, aryl, aromatic heterocyclic group or lower alkoxy.
  • substituents are halogen; hydroxy which may be protected; lower alkyl which may be substituted by halogen; lower alkoxy which may be substituted by aryl or lower alkoxy; lower alkenyl Lower alkenyloxy; Sil; acyloxy; lower alkoxycarbonyl; lower alkylthio; lower alkyl, lower alkenyl, amino optionally substituted with halogen or lower alkylsulfonyl optionally substituted with halogen; nitro; lower alkyl sulfonyl A lower alkylsulfonyloxy optionally substituted with halogen; or arylsulfonyloxy, more preferably halogen, hydroxy, lower alkyl, lower alkoxy, carboxy or lower alkoxycarbonyl.
  • aryl portion of “arylalkyl”, “arylsulfonyl”, “arylsulfonyloxy” and “arylarylcarbonyl” is the same as the above “aryl”, and phenyl is particularly preferred.
  • arylsulfonyl optionally having substituent (s) is the same as the substituent of "aryl which may have substituent (s)", and one or more arbitrary positions may be It may be substituted with a substituent. Particularly, unsubstituted one is preferred.
  • the “5- or 6-membered hetero ring” includes a 5- or 6-membered hetero ring having at least one heteroatom in the ring arbitrarily selected from 0, S and N.
  • a non-aromatic such as piperidines Rajin ring and Moruhori down ring.
  • a 5- or 6-membered hetero ring containing 1 or 2 hetero atoms refers to a “5- or 6-membered hetero ring” in the above “pyrrolyl, imidazole, pyrazol ring, Aromatic heterocycles such as pyridine, pyridazine, pyrimidine, pyrazine, isoxazolyl, oxazolyl, isothiazole, thiazolyl, furan and thiophene rings, dioxane ring, Oxathiolane ring, thiane ring, dihydropyridine ring, lipo lysine ring, lipo lin ring, imidazolidin ring, imidazoline ring, virazolidine ring, pyrazoline ring, pyridyl ring, piperazine And non-aromatic heterocycles such as morpholine rings.
  • a bond is provided at each of the 2- and 5-positions.
  • the “5- or 6-membered heterocyclic group” in Y is preferably 4-pyridyl, 2-furyl, 3-furyl, 2-phenyl, 3-phenyl, 1,2- —Dihydropyridin-1-yl, 2,3—dihydropyridazine-1-6-yl, 1,2—dihydropyrazine-1-5-yl.
  • Examples of "5- or 6-membered hetero ring which may be condensed with a benzene ring” include an indole ring, an isoindole ring, a benzimidazole ring, an indazole ring, a cinnoline ring, Phthalazine ring, quinazoline ring, benzisoxazolyl ring, benzoxazolyl ring, benzoxodiazole ring, benzothiazolyl ring, benzoisothiazolyl ring, benzofuran ring, benzothiophene ring, benzotriazolyl ring Ring, isobenzofuran ring, indolin ring, isoindrin ring and octamen ring. These may have a bond in the fused heterocycle.
  • substituents of “ring” and “5- or 6-membered heterocyclic ring optionally having one or two heteroatoms and containing one or two heteroatoms” are halogen; Lower alkyl optionally substituted with hydroxy or acyloxy; Lower alkoxy, lower alkenyl, lower alkenyl, lower alkynyl, lower alkynyloxy, lower alkynyloxy, lower alkynyloxy, lower alkenyl optionally substituted with a 5-, or 6-membered heterocyclic ring; Lower alkylthio; lower alkenylthio; halogen, lower alkyl which may have a substituent (substituent is cycloalkyl or 5- or 6-membered heterocyclic ring), substituted with halogen.
  • Amino which may be mono- or di-substituted with optionally substituted acyl, lower alkenyl, cycloalkyl or lower alkylsulfonyl; imino which may be substituted with lower alkylsulfonyl; nitro; lower; Alkylsulfonyl; aryl, 5- or 6-membered heterocycle; oxo; And the like may be mentioned, and one or more arbitrary positions may be substituted.
  • Preferable are halogen; hydroxy; lower alkyl; lower alkoxy; carboxy; lower alkoxyl propyl; amino which may be substituted with lower alkyl or lower alkenyl; and particularly preferable are lower alkyl.
  • substituents of the "optionally substituted 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms" are the same as described above, but are preferably substituted with lower alkyl Or unsubstituted.
  • a ring, B ring and / or if the C ring is a hetero ring 5-membered to the optionally having substituent W l, W 2 and / or W 3 represents a bonding means, A When the ring is a 5-membered hetero ring, W 1 represents a bond, and the bonding position of V 1 and X to the A ring is
  • Ra and R b together form one (CR e R f ) r—” means that R a and R b together with the N atom to which they are attached have a substituent May form a nitrogen-containing saturated heterocyclic ring, for example, an aziridine which may have a substituent, an azetidine which may have a substituent, or a substituent which may have a substituent Pyrrolidine, optionally substituted piperidine and optionally substituted perhydrazepine (here, the substituent is lower alkyl, lower alkoxy or amino) are included.
  • a plurality of R e and a plurality of R f may each independently represent hydrogen, lower alkyl, lower alkoxy or amino, and specifically, one (CH 2 ) 2 —,-(CH 2) 3 —, — CH (Me) (CH 2) 3 -, - CH 2 CH (OMe) (CH 2) 3 -, - (CH 2) 3 CH (NH 2) (CH 2) 2 , First and the like.
  • the present invention includes pharmaceutically acceptable salts of the compound (I) of the present invention.
  • salts of mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid and hydrobromic acid; formic acid, acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, etc.
  • Salts of organic bases such as ammonium, trimethylammonium, and triethylammonium
  • salts of alkaline metals such as sodium and calcium
  • salts of alkali metals such as calcium and magnesium Examples thereof include salts of alkaline earth metals.
  • the present invention includes solvates (preferably hydrates) of the compound (I) of the present invention.
  • the solvate includes a solvate with an organic solvent and / or water. When forming a hydrate, it may be coordinated with any number of water molecules.
  • the present invention includes all stereoisomers of the compound (I) (for example, atomers).
  • ring A is an aromatic carbon ring which may have a substituent or a 5- or 6-membered hetero ring which may have a substituent (hereinafter, ring A is A-1 Compound),
  • Ring A is a benzene ring which may have a substituent or a 6-membered hetero ring which may have a substituent (hereinafter, Ring A is A-2);
  • ring A is a benzene ring which may have a substituent
  • Ring A is a benzene ring which may have a substituent (halogen, optionally protected hydroxy, lower alkyl, lower alkoxy, carboxy or lower alkoxycarbonyl)
  • ring A is A-4 Compound, wherein the A ring is a benzene ring which may have a substituent (halogen, hydroxy or lower alkoxy) (hereinafter, the A ring is A-5)
  • ring A is a benzene ring which may be substituted with halogen (hereinafter, ring A is A-6);
  • ring B is an aromatic carbon ring which may have a substituent or a 5- or 6-membered hetero ring which may have a substituent (hereinafter, ring B is B-1 Compound),
  • ring B is a benzene ring which may have a substituent or a 6-membered hetero ring which may have a substituent (hereinafter, ring B is B-2);
  • ring B is a benzene ring which may have a substituent
  • Ring B may have a substituent (halogen, hydroxy which may be protected, lower alkyl which may have a substituent, lower alkoxy which may have a substituent, or Good lower alkoxycarbonyl)
  • a substituent halogen, hydroxy which may be protected, lower alkyl which may have a substituent, lower alkoxy which may have a substituent, or Good lower alkoxycarbonyl
  • ring B is a benzene ring which may have a substituent (hydroxy, lower alkyl, lower alkoxy or lower alkoxycarbonyl) (hereinafter, ring B is B-5);
  • ring C is an aromatic carbon ring which may have a substituent or a 5- or 6-membered hetero ring which may have a substituent (hereinafter, ring C is C-11 Compound),
  • the C ring is a benzene ring which may have a substituent or a 6-membered hetero ring containing 1 or 2 hetero atoms which may have a substituent. 2) compound,
  • Ring C has a benzene ring, which may have a substituent, a pyridine ring, which may have a substituent, a pyrimidine ring, which may have a substituent, An optionally substituted pyridazine ring or an optionally substituted pyrazine ring (hereinafter, referred to as a pyridazine ring).
  • the ring C is C-13) compound,
  • Ring C is a benzene ring, a pyridine ring, a pyrimidine ring, a pyridazine ring or a pyrazine ring (these may be substituted by halogen, lower alkyl or lower alkoxy) (hereinafter, ring C is C-14) Compound),
  • a compound in which the ring C is a benzene ring or a pyridin ring (these may be substituted with halogen, lower alkyl or lower alkoxy) (hereinafter, the C ring is C-15);
  • X is —0—, one CH 2 — or one NR l — (where R 1 is hydrogen or lower alkyl optionally having substituent (s)) (hereinafter, X is XI) Compound,
  • a compound in which X is —0— or one NH— (hereinafter, X is X 3), a compound in which X is one NH— (hereinafter, X is X 4),
  • Y is hydrogen, lower alkyl which may have a substituent, lower alkenyl which may have a substituent or cycloalkyl which may have a substituent (hereinafter, Y is Y 1) compound,
  • Y is hydrogen, lower alkyl, arylalkyl, lower alkenyl, or cycloalkyl (hereinafter, Y is Y 2);
  • Y is Y 3
  • R c and R d are each independently hydrogen, lower alkyl A lower alkenyl, lower alkoxy, aryl or heterocyclic group
  • R e is each independently hydrogen, lower alkyl, lower alkoxy or amino
  • R f is each independently hydrogen, lower alkyl, lower alkyl
  • R a and R b are R ab- 1)
  • r is 4 or 5 (hereinafter, R a and R b are R ab—
  • R a and R b are each independently hydrogen, alkyl having 1 to 3 carbons or alkoxycarbonyl having 1 to 4 carbons, or together form R c R d C;
  • a one is alkyl of one to three carbon atoms of R c and R d, the other is hydrogen, alkyl or lower alkoxy having 1 to 3 carbon atoms, 1 to 3 carbon atoms (hereinafter, the R a Contact and R b R ab— 4) compound,
  • a compound which is a lower alkoxy represented by Formulas 1 to 3 hereinafter, Ra and Rb are each Rab-5),
  • n 0 or 1
  • n 1
  • n 2
  • a compound in which A ring, B ring, C ring, X, Y, R a , R b and n are any one of the following combinations, and both V 1 and V 2 are single bonds.
  • the ring C is an aromatic carbon ring which may have a substituent or a 6-membered hetero ring which may have a substituent (hereinafter, it is assumed that the ring C is C-1 ') ) Compound, A compound wherein the C ring is C-2, a compound wherein the C ring is C-3, a compound wherein the C ring is C-14, a compound wherein the C ring is C-15,
  • R 4 , R 5 , R 6 and R 7 are each independently hydrogen, halogen, optionally protected hydroxy, lower alkyl, lower alkoxy, carboxy or lower alkoxycarbonyl (hereinafter R 4) ⁇ R 7 is R 47-1)
  • R 4, R 5, R 6 and R 7 are each independently hydrogen or halogen (hereinafter, 11 4 to 1 7 is assumed to be 1147- 2) compounds,
  • R 4 and R 5 are hydrogen, the other is halogen, and both R 6 and R 7 are hydrogen
  • R 4 to R 7 are R 47-3
  • R 8 , R 9 , R 10 and R 11 each independently represent hydrogen, halogen, hydroxy which may be protected, lower alkyl which may have a substituent, and substituent A lower alkoxy, a carboxy or a lower alkoxycarbonyl optionally having a substituent (hereinafter, R 8 to R 11 are R 811-1);
  • R 8, R 9, R 10 and R 11 are each independently hydrogen, optionally protected hydroxy, lower alkyl, lower alkoxy or lower alkoxycarbonyl (hereinafter, R 8 to R 11 are R 8 1 1—2) compound,
  • R 8 and R 1 1 are independently each human de port alkoxy, lower alkyl or lower alkoxycarbonyl, human Dorokishi independently R 9 and R 1 0 are each lower alkyl, lower alkoxy or lower alkoxycarbonyl Cal Poni Le (Hereinafter, R 8 to R 11 are R 8 11-3) R 8 is hydrogen or lower alkyl, R 9 is hydroxy, lower alkyl or lower alkoxy, R 10 is hydroxy, lower alkyl, lower alkoxy or lower alkoxycarbonyl, and R 11 is hydrogen A compound which is hydroxy or lower alkyl or lower alkoxycarbonyl (hereinafter, R 8 to R 11 are R 8 11 — 4),
  • RSR 11 is: 811-15
  • C ring, X, Y, R a, is any combination of R b and n have the following, R 4 to R 7 is R 4 7- 3, 11 8 ⁇ 11 1 1 is 13 ⁇ 4 8 1
  • a compound that is 1-4. (C-2, X2, Y2, Rab-3, nl), (C-2, X2, Y2, Rab-3, n2), (C-2, X2, Y2, Rab-4, nl), (C -2, X2, Y2, Rab-4, n2), (C-2, X2, Y3, Rab-3, nl), (C-2, X2, Y3, Rab-3, n2), (C-2 , X2, Y3, Rab-4, nl), (C-2, X2, Y3, Rab-4, nl), (C-2, X2, Y3, Rab-4, n2), (C-2, X2, Y3, Rab-4, n2), (C-2, X3, Y2, Rab-3, nl), (C-2,
  • Tables 1 to 3 show the partial structures represented by the symbols ⁇ 1, ⁇ 2, ⁇ , B1, B2, CC1, C2, ⁇ ⁇ ⁇ Tables 4 to 12 show combinations of the A ring, B ring and C ring represented by the symbols of ABC1,, ABC2,..., And Table 13 shows R a R bl, R a The combination of Ra and Rb represented by each symbol of Rb2, ⁇ 'is shown.
  • cHex represents cyclohexyl
  • cPr represents cyclopropyl.
  • RaRbl3 (ABC2, RaRbl4), (ABC2, RaRbl5) ; (ABC2, RaRbl6), (ABC2, RaRbl7), (ABC2, RaRb l8), (ABC2, RaRbl9), (ABC2, RaRb20), (ABC2, RaRb21) ), (ABC2, RaRb22), (ABC2, RaRb23), (ABC2, RaRb24), (ABC2, RaRb25), (ABC2, RaRb26), (ABC2, RaRb27), (ABC2, RaRb28), (ABC2, RaRb29), (ABC2, RaRb30), (ABC2, RaRb31), (ABC2, RaRb32), (ABC3, RaRb l), (ABC3, RaRb2), (ABC3, RaRb3), (ABC3, RaRb4), (ABC3, RaRb5), (ABC3, RaRb6), (ABC3, RaRb7), (ABC3,
  • AR R (((() RaC7 ⁇ Rb7AB27 ⁇ 9e 4 ⁇ ⁇ 24 Ban! ⁇ aHhA ⁇ E--
  • RabRl3C9AB RaRb22l4 (ABC295, RaRb4), (ABC295, RaRb5), (ABC295, RaRb6), (ABC295, RaRb7), (ABC295, RaRb8), (ABC295, RaRb9), (ABC295, RaRb lO), (ABC295, RaRbl l), (ABC295, RaRbl2), (ABC295, RaRl 3), (ABC295, RaRb l4), (ABC295, RaRb l5), (ABC295, RaRbl6), (ABC295, RaRb l7), (ABC295, RaRbl8) ; (ABC295, RaRbl9), (ABC295, RaRb20), (ABC295, RaRb21), (ABC295, RaRb22) ; (ABC295, RaRb23) '(ABC295, RaRb24), (ABC295, RaRb25), (AB
  • RaRb28 (ABC309, RaRb29), (ABC309, RaRb30), (ABC309, RaRb31), (ABC309, RaRb32), (ABC310, RaRbl), (ABC310, RaRb2), (ABC310, RaRb3), (ABC310, RaRb4) , (ABC310, RaRb5), (ABC310, RaRb6), (ABC310, RaRb7) ; (ABC310, RaRb8), (ABC310, RaRb9), (ABC310, RaRb lO), (ABC310, RaRbl l), (ABC310, RaRbl2) , (ABC310, RaRbl3), (ABC310, RaRbl4), (ABC310, RaRbl5), (ABC310, RaRb l6), (ABC310, Ra bl7), (ABC310, RaRb l8), (ABC310, RaRbl5)

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Abstract

L'invention porte sur ses composés de formule générale (I), leurs précurseurs, sels ou solvates et sur des compositions médicamenteuses les contenant. Dans la formule (I): A, B et C sont chacun un cycle aromatique carbo ou héréro ou analogue, sous réserve que si A est un hétérocycle à 5 éléments facultativement substitué, W1 soit une liaison, la même condition s'appliquant dans le cas de B et W2, et dans le cas de C et W3; X et X' sont chacun -O-, -NH-, ou analogue; Y est alkyle inférieur, alcényle inférieur ou analogue; V1 et V2 sont chacun une liaison simple ou analogue; Ra et Rb sont chacun H, alkyle inférieur, alcényle inférieur ou analogue; ou bien s'unissent pour former RcRdC= ou (CReRf)r-; Re et Rf sont chacun H, alkyle inférieur ou analogue; n est 0 à 2; et r est 2 à 6.
PCT/JP2000/004726 1999-07-23 2000-07-14 Composes tricycliques et compositions medicamenteuses les contenant WO2001007401A1 (fr)

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US7053088B2 (en) 2002-05-22 2006-05-30 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7144888B2 (en) 2002-08-08 2006-12-05 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7301022B2 (en) 2005-02-15 2007-11-27 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7511044B2 (en) 2004-02-11 2009-03-31 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7534798B2 (en) 2004-02-11 2009-05-19 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7994185B2 (en) 2008-05-06 2011-08-09 Glaxo Smith Kline LLC Benzene sulfonamide thiazole and oxazole compounds
EP2583678A2 (fr) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Immunopotentiateurs de petites molécules et dosages pour leur détection
US10391094B2 (en) 2010-11-07 2019-08-27 Impact Biomedicines, Inc. Compositions and methods for treating myelofibrosis

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WO1998004508A1 (fr) * 1996-07-31 1998-02-05 Shionogi & Co., Ltd. NOUVEAUX COMPOSES DE p-TERPHENYL

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JPH01191154A (ja) * 1988-01-27 1989-08-01 Canon Inc 電子写真感光体
WO1998004508A1 (fr) * 1996-07-31 1998-02-05 Shionogi & Co., Ltd. NOUVEAUX COMPOSES DE p-TERPHENYL

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7524874B2 (en) 2002-05-22 2009-04-28 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7053088B2 (en) 2002-05-22 2006-05-30 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7396831B2 (en) 2002-05-22 2008-07-08 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7144888B2 (en) 2002-08-08 2006-12-05 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7148221B2 (en) 2002-08-08 2006-12-12 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7332511B2 (en) 2002-08-08 2008-02-19 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7534798B2 (en) 2004-02-11 2009-05-19 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7511044B2 (en) 2004-02-11 2009-03-31 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US8227469B2 (en) 2004-02-11 2012-07-24 Amgen Inc. Vanilloid receptor ligands and their use in treatments
EP2583678A2 (fr) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Immunopotentiateurs de petites molécules et dosages pour leur détection
US7301022B2 (en) 2005-02-15 2007-11-27 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US7994185B2 (en) 2008-05-06 2011-08-09 Glaxo Smith Kline LLC Benzene sulfonamide thiazole and oxazole compounds
US8415345B2 (en) 2008-05-06 2013-04-09 Glaxo SmithKline LLC Benzene sulfonamide thiazole and oxazole compounds
US8642759B2 (en) 2008-05-06 2014-02-04 Glaxosmithkline Llc Benzene sulfonamide thiazole and oxazole compounds
US9233956B2 (en) 2008-05-06 2016-01-12 Novartis Ag Benzene sulfonamide thiazole and oxazole compounds
US10391094B2 (en) 2010-11-07 2019-08-27 Impact Biomedicines, Inc. Compositions and methods for treating myelofibrosis

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