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    Substituted sulfonylaminoarylmethyl cyclopropanecarboxamide as VR1 receptor antagonists
    7.
    发明授权
    Substituted sulfonylaminoarylmethyl cyclopropanecarboxamide as VR1 receptor antagonists 失效

    公开(公告)号：US07915448B2

    公开(公告)日：2011-03-29

    申请号：US12578061

    申请日：2009-10-13

    申请人： Takeshi Hanazawa ,  Misato Hirano ,  Tadashi Inoue ,  Satoshi Nagayama ,  Kazunari Nakao ,  Yuji Shishido ,  Hirotaka Tanaka

    发明人： Takeshi Hanazawa ,  Misato Hirano ,  Tadashi Inoue ,  Satoshi Nagayama ,  Kazunari Nakao ,  Yuji Shishido ,  Hirotaka Tanaka

    IPC分类号： C07C311/03 ,  A61K31/18

    CPC分类号： C07C61/28 ,  C07C61/40 ,  C07C311/08 ,  C07C317/44 ,  C07C323/62 ,  C07C2601/02 ,  C07D213/26 ,  C07D213/56 ,  C07D213/74 ,  C07D213/76

    摘要： This invention provides a compound of the formula (I): wherein A and B are independently CR12 or N; D and E are each independently CR9 or N; R1 represents (C1-C6)alkyl; R2 represents hydrogen, halogen, hydroxy, (C1-C6) alkyl, halo(C1-C6) alkyl, hydroxy(C1-C6) alkyl, (C1-C6)alkoxy or (C1-C6)alkoxy-(C1-C6)alkyl; R3, R4, R5, R6, R10 and R11 each independently represent hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl or (C1-C6)alkoxy-(C1-C6)alkyl; or R3 and R4 are taken together with the carbon atom to which they are attached to form a 3- to 7-membered carbocyclic ring or heterocyclic ring in which one or two non-adjacent carbon atoms are optionally replaced by an oxygen atom, a sulfur atom or NH; R7 and R9 each independently represent hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkoxy, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, NH2, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2N—(C1-C6)alkoxy, (C1-C6)alkyl-NH—(C1-C6)alkoxy, [(C1-C6)alkyl]2N(C1-C6)alkoxy; H2N—(C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkyl-NH—(C1-C6)alkoxy-(C1-C6)alkyl, [(C1-C6)alkyl]2N(C1-C6)alkoxy-(C1-C6)alkyl or 5- or 6- membered heterocyclic ring containing at least one nitrogen atom; R8 represents halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkoxy, halo(C1-C6)alkylsulfonyl, halo(C1-C6)alkylsulfinyl, halo(C1-C6)alkoxy, halo(C1-C6)alkylthio, [(C1-C6)alkyl]NH— or [(C1-C6)alkyl]2N—; or R7 and R8, when E is CR9, are taken together with the carbon atoms to which they are attached form a 5-8 membered carbocyclic or heterocyclic ring, in which one or two non-adjacent carbon atoms are optionally replaced by oxygen, sulfur, N or NH groups, wherein the carbocyclic ring or the heterocyclic ring is unsubstituted or substituted with one or more substituents each independently selected from the group consisting of hydroxy, (C1-C6)alkyl, (C1-C6)alkoxy and hydroxy(C1-C6)alkyl; and R12 represents hydrogen, halogen, (C1-C6)alkyl or hydroxy(C1-C6)alkyl; or a pharmaceutically acceptable salt or solvate thereof.

    Substituted N-sulfonylaminophenylethyl-2-phenoxyacetamide compounds as VR1 receptor antagonists
    9.
    发明申请
    Substituted N-sulfonylaminophenylethyl-2-phenoxyacetamide compounds as VR1 receptor antagonists 失效

    公开(公告)号：US20060205980A1

    公开(公告)日：2006-09-14

    申请号：US11372706

    申请日：2006-03-10

    申请人： Takeshi Hanazawa ,  Misato Hirano ,  Tadashi Inoue ,  Satoshi Nagayama ,  Kazunari Nakao ,  Yuji Shishido ,  Hirotaka Tanaka

    发明人： Takeshi Hanazawa ,  Misato Hirano ,  Tadashi Inoue ,  Satoshi Nagayama ,  Kazunari Nakao ,  Yuji Shishido ,  Hirotaka Tanaka

    IPC分类号： C07C311/46

    CPC分类号： C07C311/08

    摘要： This invention provides a compound of the formula (I): wherein R1 represents (C1-C6)alkyl; R2 represents a hydrogen atom, a halogen atom, a hydroxy group, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkyl or halo(C1-C6)alkyl; R3 represents a halogen atom, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkoxy, halo(C1-C6)alkyl, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, [(C1-C6)alkyl]NH—, or [(C1-C6)alkyl]2N—; R4 represents a halogen atom, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkoxy, [(C1-C6)alkyl]NH—, or [(C1-C6)alkyl]2N—; R5 represents a halogen atom, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkoxy, halo(C1-C6)alkyl, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2N—(C1-C6)alkoxy, (C1-C6)alkyl-NH—(C1-C6)alkoxy, [(C1-C6)alkyl]2N(C1-C6)alkoxy, H2N—(C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkyl-NH—(C1-C6)alkoxy-(C1-C6)alkyl, or [(C1-C6)alkyl]2N(C1-C6)alkoxy-(C1-C6)alkyl; and * indicates a chiral centre; or a pharmaceutically acceptable salt or solvate thereof. These compounds are useful for the treatment of disease conditions caused by overactivation of VR1 receptor such of pain, or the like in mammalian. This invention also provides a pharmaceutical composition comprising the above compound.

    Substituted sulfonylaminoarylmethyl cyclopropanecarboxamide as VR1 receptor antagonists
    10.
    发明申请
    Substituted sulfonylaminoarylmethyl cyclopropanecarboxamide as VR1 receptor antagonists 失效

    公开(公告)号：US20060211741A1

    公开(公告)日：2006-09-21

    申请号：US11384127

    申请日：2006-03-17

    申请人： Takeshi Hanazawa ,  Misato Hirano ,  Tadashi Inoue ,  Satoshi Nagayama ,  Kazunari Nakao ,  Yuji Shishido ,  Hirotaka Tanaka

    发明人： Takeshi Hanazawa ,  Misato Hirano ,  Tadashi Inoue ,  Satoshi Nagayama ,  Kazunari Nakao ,  Yuji Shishido ,  Hirotaka Tanaka

    IPC分类号： A61K31/4412 ,  A61K31/18 ,  C07D213/75

    CPC分类号： C07C61/28 ,  C07C61/40 ,  C07C311/08 ,  C07C317/44 ,  C07C323/62 ,  C07C2601/02 ,  C07D213/26 ,  C07D213/56 ,  C07D213/74 ,  C07D213/76

    摘要： This invention provides a compound of the formula (I): wherein A and B are independently CR12 or N; D and E are each independently CR9 or N; R1 represents (C1-C6)alkyl; R2 represents hydrogen, halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy or (C1-C6)alkoxy-(C1-C6)alkyl; R3, R4, R5, R6, R10 and R11 each independently represent hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl or (C1-C6)alkoxy-(C1-C6)alkyl; or R3 and R4 are taken together with the carbon atom to which they are attached to form a 3- to 7-membered carbocyclic ring or heterocyclic ring in which one or two non-adjacent carbon atoms are optionally replaced by an oxygen atom, a sulfur atom or NH; R7 and R9 each independently represent hydrogen, halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkoxy, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C6)alkylsulfonyl, NH2, [(C1-C6)alkyl]NH—, [(C1-C6)alkyl]2N—, H2N—(C1-C6)alkoxy, (C1-C6)alkyl-NH—(C1-C6)alkoxy, [(C1-C6)alkyl]2N(C1-C6)alkoxy; H2N—(C1-C6)alkoxy-(C1-C6)alkyl, (C1C6)alkyl-NH—(C1-C6)alkoxy-(C1-C6)alkyl, [(C1-C6)alkyl]2N(C1-C6)alkoxy-(C1-C6)alkyl or 5- or 6-membered heterocyclic ring containing at least one nitrogen atom; R8 represents halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C6)alkoxy-(C1-C6)alkyl, (C1-C6)alkoxy-(C1-C6)alkoxy, halo(C1-C6)alkylsulfonyl, halo(C1-C6)alkylsulfinyl, halo(C1-C6)alkoxy, halo(C1-C6)alkylthio, [(C1-C6)alkyl]NH— or [(C1-C6)alkyl]2N—; or R7 and R8, when E is CR9, are taken together with the carbon atoms to which they are attached form a 5-8 membered carbocyclic or heterocyclic ring, in which one or two non-adjacent carbon atoms are optionally replaced by oxygen, sulfur, N or NH groups, wherein the carbocyclic ring or the heterocyclic ring is unsubstituted or substituted with one or more substituents each independently selected from the group consisting of hydroxy, (C1-C6)alkyl, (C1-C6)alkoxy and hydroxy(C1-C6)alkyl; and R12 represents hydrogen, halogen, (C1-C6)alkyl or hydroxy(C1-C6)alkyl; or a pharmaceutically acceptable salt or solvate thereof. These compounds are useful for the treatment of disease conditions caused by overactivation of VR1 receptor such of pain, or the like in mammalian. This invention also provides a pharmaceutical composition comprising the above compound.