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    PHARMACEUTICAL COMBINATIONS
    4.
    发明申请
    PHARMACEUTICAL COMBINATIONS 审中-公开
    药物组合

    公开(公告)号：US20090263398A1

    公开(公告)日：2009-10-22

    申请号：US12373713

    申请日：2007-07-13

    申请人： John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Neil James Gallagher ,  Jayne Elizabeth Curry

    发明人： John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Neil James Gallagher ,  Jayne Elizabeth Curry

    IPC分类号： A61K31/415 ,  A61K31/422 ,  A61K31/4178 ,  A61K31/4155 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/454 ,  A61K31/506 ,  A61K31/541 ,  A61K31/439 ,  A61P35/00 ,  A61K39/395

    CPC分类号： A61K31/4453 ,  A61K31/415 ,  A61K2300/00

    摘要： The invention provides a combination comprising an ancillary compound and a compound having the formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NR9(C═O) or 0(C═O) wherein R9 is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy; or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy; R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C1-4 alkoxy.

    摘要翻译： 本发明提供包含辅助化合物和具有式（O）的化合物的组合：或其盐或互变异构体或N-氧化物或溶剂合物; 其中X为基团R 1 -A-NR 4 - 或5或6元碳环或杂环; A为键，SO 2，C-O，NR 9（C-O）或O（C-O），其中R 9为氢或任选被羟基或C 1-4烷氧基取代的C 1-4烃基; Y是长度为1,2或3个碳原子的键或亚烷基链; R1是氢; 具有3至12个环成员的碳环或杂环基; 或任选被一个或多个选自卤素，羟基，C 1-4烃氧基，氨基，一或二-C 1-4烃基氨基的取代基取代的C 1-8烃基，以及具有3-12个环成员的碳环或杂环基， 并且其中所述烃基的1或2个碳原子可以任选地被选自O，S，NH，SO，SO 2的原子或基团取代; R2是氢; 卤素; C 1-4烷氧基; 或任选被卤素，羟基或C 1-4烷氧基取代的C 1-4烃基; R 3选自具有3至12个环成员的氢和碳环和杂环基; R4是氢或任选被卤素，羟基或C 1-4烷氧基取代的C 1-4烃基。

    Combinations of pyrazole kinase inhibitors
    5.
    发明授权
    Combinations of pyrazole kinase inhibitors 有权
    吡唑激酶抑制剂的组合

    公开(公告)号：US08404718B2

    公开(公告)日：2013-03-26

    申请号：US12752772

    申请日：2010-04-01

    申请人： Jayne Elizabeth Curry ,  John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Kyla Merriom Thompson ,  Paul Graham Wyatt

    发明人： Jayne Elizabeth Curry ,  John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Kyla Merriom Thompson ,  Paul Graham Wyatt

    IPC分类号： A61K31/4465 ,  A61K31/4468 ,  A61K31/454 ,  C07D401/12

    CPC分类号： A61K45/06 ,  A61K31/415 ,  A61K31/4439 ,  A61K31/497 ,  A61K33/24 ,  A61K2300/00

    摘要： The invention provides a combination comprising a cytotoxic compound, a signalling inhibitor, an ancillary agent, or two or more further anti-cancer agents, and a compound having the formula (Ib): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R1-A-NR4—; A is a bond, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from fluorine, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

    摘要翻译： 本发明提供了包含细胞毒性化合物，信号传导抑制剂，辅助剂或两种或更多种其它抗癌剂和具有式（Ib）的化合物或其盐或互变异构体或N-氧化物或溶剂合物的组合： 其中X是基团R 1 -A-NR 4 - ; A是键，C = O，NR g（C = O）或O（C = O），其中R g是氢或任选被羟基或C 1-4烷氧基取代的C 1-4烃基; Y是长度为1,2或3个碳原子的键或亚烷基链; R1是具有3-12个环成员的碳环或杂环基; 或任选被一个或多个选自氟，羟基，C 1-4烃氧基，氨基，一或二-C 1-4烃基氨基的取代基取代的C 1-8烃基，以及具有3-12个环成员的碳环或杂环基， 并且其中所述烃基的1或2个碳原子可以任选地被选自O，S，NH，SO，SO 2的原子或基团取代; R2是氢; 卤素; C 1-4烷氧基（如甲氧基）; 或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基; R3选自具有3至12个环成员的碳环和杂环基; 和R 4是氢或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基。

    Combinations of Pyrazole Kinase Inhibitors and Further Antitumor Agents
    6.
    发明申请
    Combinations of Pyrazole Kinase Inhibitors and Further Antitumor Agents 审中-公开
    吡唑激酶抑制剂和其他抗肿瘤剂的组合

    公开(公告)号：US20080161355A1

    公开(公告)日：2008-07-03

    申请号：US11814455

    申请日：2006-01-20

    申请人： Jayne Elizabeth Curry ,  John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Kyla Merriom Thompson ,  Paul Graham Wyatt

    发明人： Jayne Elizabeth Curry ,  John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Kyla Merriom Thompson ,  Paul Graham Wyatt

    IPC分类号： A61K31/415 ,  A61K31/454 ,  A61P35/00 ,  A61P35/02

    CPC分类号： A61K31/44 ,  A61K31/00 ,  A61K31/341 ,  A61K31/4155 ,  A61K31/496 ,  A61K31/5355 ,  A61K2300/00

    摘要： The invention provides a combination of a compound having the formula (0) and two or more further anti-cancer agents: or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NR9(C═O) or 0(C═O) wherein R9 is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

    摘要翻译： 本发明提供具有式（O）的化合物和两种或更多种其它抗癌剂或其盐或互变异构体或N-氧化物或溶剂合物的组合; 其中X为基团R 1 -A-NR 4 - 或5或6元碳环或杂环; A是键，SO 2，CO，NR 9（CO）或O（CO），其中R 9是氢或C 1-4烷基， 任选被羟基或C 1-4烷氧基取代的烃基; Y是长度为1,2或3个碳原子的键或亚烷基链; R 1是氢; 具有3至12个环成员的碳环或杂环基; 或任选被一个或多个选自卤素（例如氟），羟基，C 1-4 - 烷氧基，氨基，单 - 或四个取代基取代的C 1-8烷基 二-C 1-4烃基氨基和具有3-12个环成员的碳环或杂环基团，并且其中烃基的1或2个碳原子可以任选地被原子或基团取代 选自O，S，NH，SO，SO 2; R 2是氢; 卤素; C 1-4烷氧基（如甲氧基）; 或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烷基; R 3选自具有3至12个环成员的氢和碳环和杂环基; 和R 4是氢或任选被卤素（例如氟），羟基或C 1-4烷氧基取代的C 1-4烷基 （如甲氧基）。

    Pharmaceutical Compounds
    7.
    发明申请
    Pharmaceutical Compounds 审中-公开
    药物化合物

    公开(公告)号：US20090036435A1

    公开(公告)日：2009-02-05

    申请号：US11814461

    申请日：2006-01-20

    申请人： Jayne Elizabeth Curry ,  John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Kyla Merriom Thompson ,  Paul Graham Wyatt

    发明人： Jayne Elizabeth Curry ,  John Francis Lyons ,  Matthew Simon Squires ,  Neil Thomas Thompson ,  Kyla Merriom Thompson ,  Paul Graham Wyatt

    IPC分类号： A61K31/541 ,  A61K31/415 ,  A61K31/41 ,  A61K31/4439 ,  A61K31/4196 ,  A61K31/454 ,  A61K31/496 ,  A61P35/00 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/5377 ,  A61K31/497 ,  A61K31/422 ,  A61K31/4545

    CPC分类号： A61K31/5685 ,  A61K31/135 ,  A61K31/138 ,  A61K31/195 ,  A61K31/255 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4188 ,  A61K31/4196 ,  A61K31/4535 ,  A61K31/565 ,  A61K31/675 ,  A61K39/395 ,  A61K45/06 ,  A61K2300/00

    摘要： The invention provides a combination of an ancillary agent and a compound having the formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein the ancillary agent is selected from: a monoclonal antibody, an alkylating agent, an anticancer agent, a further CDK inhibitor and a hormone, hormone agonist, hormone antagonist or hormone modulating agent; X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NR9(C═O) or 0(C═O) wherein R9 is hydrogen or Ĉhydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, Ĉhydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; Ĉalkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a Ĉhydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

    摘要翻译： 本发明提供了辅助剂和具有式（O）的化合物或其盐或互变异构体或N-氧化物或溶剂合物的组合： 其中所述辅助剂选自：单克隆抗体，烷化剂，抗癌剂，另外的CDK抑制剂和激素，激素激动剂，激素拮抗剂或激素调节剂; X是R1-A-NR4-基团或5或6元碳环或杂环; A是键，SO 2，C-O，NR 9（C-O）或O（C-O），其中R 9是氢或任选被羟基或C 1-4烷氧基取代的羟基; Y是长度为1,2或3个碳原子的键或亚烷基链; R1是氢; 具有3至12个环成员的碳环或杂环基; 或任选被一个或多个选自卤素（例如氟），羟基，羟基氧基，氨基，单 - 或二-C 1-4烃基氨基的取代基取代的C 1-8烃基和具有3-12个环成员的碳环或杂环基 并且其中烃基中的1或2个碳原子可以任选地被选自O，S，NH，SO，SO 2的原子或基团取代; R2是氢; 卤素; Ĉ烷氧基（如甲氧基）; 或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基; R 3选自具有3至12个环成员的氢和碳环和杂环基; 和R 4是氢或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的烃基。

    Pharmaceutical combinations
    9.
    发明授权
    Pharmaceutical combinations 有权
    药物组合

    公开(公告)号：US08277807B2

    公开(公告)日：2012-10-02

    申请号：US12445141

    申请日：2007-10-12

    申请人： Neil James Gallagher ,  John Francis Lyons ,  Neil Thomas Thompson ,  Stephen Murray Yule ,  Christopher William Murray

    发明人： Neil James Gallagher ,  John Francis Lyons ,  Neil Thomas Thompson ,  Stephen Murray Yule ,  Christopher William Murray

    IPC分类号： A61K31/404 ,  A61K31/4035 ,  A61K31/47 ,  A61K31/472 ,  A61K31/438 ,  A61K31/5377 ,  A61K39/395 ,  A61K31/4745

    CPC分类号： A61K45/06 ,  A61K31/403 ,  A61K31/4035 ,  A61K2300/00

    摘要： The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group —(O)n—R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 inhibitors.

    摘要翻译： 本发明提供包含（或基本上由）一种或多种辅助化合物和式（I）化合物或其盐，互变异构体，溶剂合物和N-氧化物的组合; 其中R1是羟基或氢; R2是羟基; 甲氧基或氢; 条件是R 1和R 2中的至少一个是羟基; R3选自氢; 卤素; 氰基; 任选取代的C 1-5烃基和任选取代的C 1-5烃氧基; R4选自氢; 其中n为0或1，R7为任选取代的无环C 1-5烃基或具有3至7个环成员的单环碳环或杂环基团 - （O）n -R 7基团; 卤素; 氰基; 羟基; 氨基; 和任选取代的单或二-C 1-5烃基 - 氨基; 或R 3和R 4一起形成5至7个环成员的单环碳环或杂环; 并且NR 5 R 6形成具有8至12个环成员的任选取代的双环杂环基，其中多达5个环成员是选自氧，氮和硫的杂原子。 这些组合具有作为Hsp90抑制剂的活性。

    PHARMACEUTICAL COMBINATIONS
    10.
    发明申请
    PHARMACEUTICAL COMBINATIONS 有权
    药物组合

    公开(公告)号：US20110105501A1

    公开(公告)日：2011-05-05

    申请号：US12445136

    申请日：2007-10-12

    申请人： Neil James Gallagher ,  John Francis Lyons ,  Neil Thomas Thompson ,  Stephen Murray Yule ,  Christopher William Murray

    发明人： Neil James Gallagher ,  John Francis Lyons ,  Neil Thomas Thompson ,  Stephen Murray Yule ,  Christopher William Murray

    IPC分类号： A61K31/4035 ,  A61K31/438 ,  A61K31/5377 ,  A61K31/496 ,  A61P31/12 ,  A61P35/00

    CPC分类号： C07D401/14 ,  A61K31/403 ,  A61K31/438 ,  A61K31/439 ,  A61K31/496 ,  A61K31/5375 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D401/04 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10 ,  A61K2300/00

    摘要： The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group —(O)n—R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase and/or aurora kinase inhibitors.

    摘要翻译： 本发明提供包含（或基本上由）一种或多种辅助化合物和式（I）化合物或其盐，互变异构体，溶剂合物和N-氧化物的组合; 其中R1是羟基或氢; R2是羟基; 甲氧基或氢; 条件是R 1和R 2中的至少一个是羟基; R3选自氢; 卤素; 氰基; 任选取代的C 1-5烃基和任选取代的C 1-5烃氧基; R4选自氢; 其中n为0或1，R7为任选取代的无环C 1-5烃基或具有3至7个环成员的单环碳环或杂环基团 - （O）n -R 7基团; 卤素; 氰基; 羟基; 氨基; 和任选取代的单或二-C 1-5烃基 - 氨基; 或R 3和R 4一起形成5至7个环成员的单环碳环或杂环; 并且NR 5 R 6形成具有8至12个环成员的任选取代的双环杂环基，其中多达5个环成员是选自氧，氮和硫的杂原子。 这些组合具有作为Hsp90和/或糖原合酶激酶-3和/或细胞周期蛋白依赖性激酶和/或极光激酶抑制剂的活性。