公开(公告)号：US08530469B2

公开(公告)日：2013-09-10

申请号：US13271678

申请日：2011-10-12

申请人： Gianni Chessari ,  Miles Stuart Congreve ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Robert Downham ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

发明人： Gianni Chessari ,  Miles Stuart Congreve ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Robert Downham ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

IPC分类号： A61K31/4035 ,  A61K31/47 ,  A61K31/496 ,  A61K31/5377 ,  C07D209/04 ,  C07D215/00 ,  C07D217/00 ,  C07D227/00 ,  C07D241/00 ,  C07D265/30 ,  C07D401/02 ,  C07D471/00

CPC分类号： C07D401/12 ,  C07C65/21 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10

摘要： The invention provides a combination comprising an Hsp90 inhibitor compound of the formula (VII): or tautomer or salt thereof and one or more therapeutic agents selected from topoisomerase I inhibitors; antimetabolites; tubulin targeting agents; DNA binder and topoisomerase II inhibitors; alkylating agents; monoclonal antibodies; anti-hormones; signal transduction inhibitors; proteasome inhibitors; DNA methyl transferases; cytokines; retinoids and HDAC or HAT modulators.

摘要翻译： 本发明提供了包含式（VII）的Hsp90抑制剂化合物或其互变异构体或其盐和选自拓扑异构酶I抑制剂的一种或多种治疗剂的组合; 抗代谢药物 微管蛋白靶向剂; DNA结合剂和拓扑异构酶II抑制剂; 烷基化剂; 单克隆抗体 抗激素; 信号转导抑制剂; 蛋白酶体抑制剂; DNA甲基转移酶; 细胞因子; 类视色素和HDAC或HAT调节剂。

公开(公告)号：US08106057B2

公开(公告)日：2012-01-31

申请号：US12782996

申请日：2010-05-19

申请人： Gianni Chessari ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Robert Downham ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

发明人： Gianni Chessari ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Robert Downham ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

IPC分类号： A61K31/497 ,  A61K31/445 ,  A61K31/405

CPC分类号： C07D209/44 ,  C07D401/04 ,  C07D401/12

摘要： This invention provides methods for treating cancer, particularly hematopoietic tumors of lymphoid or myeloid lineage, prostate cancer, lung cancer, gastrointestinal stromal tumor, breast cancer and melanoma, which comprise administering to the mammal a compound, salt, hydrate, tautomer or N-oxide according to formula (I): and in particular, those of subgenus VIIa These compounds inhibit or modulate the activity of the heat shock protein Hsp90.

摘要翻译： 本发明提供了治疗癌症，特别是淋巴或骨髓谱系造血肿瘤，前列腺癌，肺癌，胃肠道间质瘤，乳腺癌和黑素瘤的方法，其包括向哺乳动物施用化合物，盐，水合物，互变异构体或N-氧化物 根据式（I）：特别是亚属VIIa的化合物这些化合物抑制或调节热休克蛋白Hsp90的活性。

公开(公告)号：US20100286167A1

公开(公告)日：2010-11-11

申请号：US12782996

申请日：2010-05-19

申请人： Gianni Chessari ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Robert Downham ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

发明人： Gianni Chessari ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Robert Downham ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

IPC分类号： A61K31/496 ,  A61K31/404 ,  A61K31/454 ,  A61P35/00 ,  A61P35/04

CPC分类号： C07D209/44 ,  C07D401/04 ,  C07D401/12

摘要： This invention provides methods for treating cancer, particularly hematopoietic tumors of lymphoid or myeloid lineage, prostate cancer, lung cancer, gastrointestinal stromal tumor, breast cancer and melanoma, which comprise administering to the mammal a compound, salt, hydrate, tautomer or N-oxide according to formula (I): and in particular, those of subgenus VIIa These compounds inhibit or modulate the activity of the heat shock protein Hsp90.

摘要翻译： 本发明提供了治疗癌症，特别是淋巴或骨髓谱系造血肿瘤，前列腺癌，肺癌，胃肠道间质瘤，乳腺癌和黑素瘤的方法，其包括向哺乳动物施用化合物，盐，水合物，互变异构体或N-氧化物 根据式（I）：特别是亚属VIIa的化合物这些化合物抑制或调节热休克蛋白Hsp90的活性。

公开(公告)号：US07754725B2

公开(公告)日：2010-07-13

申请号：US11680818

申请日：2007-03-01

申请人： Gianni Chessari ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Robert Downham ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

发明人： Gianni Chessari ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Robert Downham ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

IPC分类号： C07D209/44 ,  A61K31/4035 ,  A61K31/496 ,  A61K31/454

CPC分类号： C07D209/44 ,  C07D401/04 ,  C07D401/12

摘要： Compounds having the formula (I): and in particular, those of subgenus VIIa are disclosed as inhibits or modulators of the activity of the heat shock protein Hsp90. As such they are useful for treating cancer, particularly hematopoietic tumors of lymphoid or myeloid lineage, prostate cancer, lung cancer, gastrointestinal stromal tumor, breast cancer and melanoma.

摘要翻译： 公开了具有式（I）：特别是亚属VIIa的化合物作为热休克蛋白Hsp90的活性的抑制剂或调节剂。 因此，它们可用于治疗癌症，特别是淋巴或骨髓谱系的造血肿瘤，前列腺癌，肺癌，胃肠道间质瘤，乳腺癌和黑素瘤。

公开(公告)号：US08101648B2

公开(公告)日：2012-01-24

申请号：US11911490

申请日：2006-04-13

申请人： Gianni Chessari ,  Miles Stuart Congreve ,  Eva Figueroa Navarro ,  Martyn Frederickson ,  Christopher Murray ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Michael Alistair O'Brien ,  Andrew James Woodhead ,  Robert Downham ,  Theresa Rachel Phillips

发明人： Gianni Chessari ,  Miles Stuart Congreve ,  Eva Figueroa Navarro ,  Martyn Frederickson ,  Christopher Murray ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Michael Alistair O'Brien ,  Andrew James Woodhead ,  Robert Downham ,  Theresa Rachel Phillips

IPC分类号： A01N43/38 ,  A61K31/40 ,  C07D209/44

CPC分类号： C07D401/12 ,  C07C65/21 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10

摘要： The invention provides compounds of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydrogen; R2 is hydroxy or methoxy; 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 compounds have activity as Hsp90 inhibitors.

摘要翻译： 本发明提供式（I）的化合物：或其盐，互变异构体，溶剂合物和N-氧化物; 其中R1是氢; R2是羟基或甲氧基; 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。 该化合物具有作为Hsp90抑制剂的活性。

公开(公告)号：US20090215772A1

公开(公告)日：2009-08-27

申请号：US11911490

申请日：2006-04-13

申请人： Gianni Chessari ,  Miles Stuart Congreve ,  Eva Figueroa Navarro ,  Martyn Frederickson ,  Christopher Murray ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Michael Alistair O'Brien ,  Andrew James Woodhead ,  Robert Downham ,  Theresa Rachel Phillips

发明人： Gianni Chessari ,  Miles Stuart Congreve ,  Eva Figueroa Navarro ,  Martyn Frederickson ,  Christopher Murray ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Michael Alistair O'Brien ,  Andrew James Woodhead ,  Robert Downham ,  Theresa Rachel Phillips

IPC分类号： A61K31/5377 ,  C07D209/44 ,  A61K31/403 ,  A61K31/454 ,  C07D401/02 ,  C07D403/02 ,  A61K31/497 ,  C07D413/14

CPC分类号： C07D401/12 ,  C07C65/21 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10

摘要： The invention provides compounds 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 hydrocarbylamino; 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 compounds have activity as Hsp90 inhibitors.

摘要翻译： 本发明提供式（I）的化合物：或其盐，互变异构体，溶剂合物和N-氧化物; 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; 和任选取代的一或二-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。 该化合物具有作为Hsp90抑制剂的活性。

公开(公告)号：US20080306054A1

公开(公告)日：2008-12-11

申请号：US11911447

申请日：2006-04-13

申请人： Gianni Chessari ,  Miles Stuart Congreve ,  Eva Figueroa Navarro ,  Martyn Frederickson ,  Christopher Murray ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Michael Alistair O'Brien ,  Andrew James Woodhead

发明人： Gianni Chessari ,  Miles Stuart Congreve ,  Eva Figueroa Navarro ,  Martyn Frederickson ,  Christopher Murray ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Michael Alistair O'Brien ,  Andrew James Woodhead

IPC分类号： A61K31/54 ,  C07D241/04 ,  A61K31/495 ,  A61K31/5375 ,  A61K31/435 ,  C07D211/06 ,  C07D265/30 ,  C07D279/12

CPC分类号： C07D401/12 ,  C07C65/21 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10

摘要： The invention provides a compound for use as an inhibitor of Hsp90, the compound having 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; C1-5 hydrocarbyl and C1-5 hydrocarbyloxy; wherein the C1-5 hydrocarbyl and C1-5 hydrocarbyloxy moieties are each optionally substituted by one or more substituents selected from hydroxy, halogen, C1-2 alkoxy, amino, mono- and di-C1-2 alkylamino, and aryl and heteroaryl groups of 5 to 12 ring members; R4 is selected from hydrogen; a group —(O)n—R7 where n is 0 or 1 and R7 is an acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and mono- or di-C1-5 hydrocarbyl-amino, wherein the acyclic C1-5 hydrocarbyl group and the mono and di-C1-5 hydrocarbylamino moieties in each instance are optionally substituted by one or more substituents selected from hydroxy, halogen, C1-2 alkoxy, amino, mono- and di-C1-2 alkylamino, and aryl and heteroaryl groups of 5 to 12 ring members; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and R5 and R6 are as defined in the claims.

摘要翻译： 本发明提供用作Hsp90抑制剂的化合物，具有式（I）的化合物：或其盐，互变异构体，溶剂合物和N-氧化物; 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; C 1-5烃基和C 1-5烃氧基; 其中C 1-5烃基和C 1-5烃氧基部分各自任选被一个或多个选自羟基，卤素，C 1-2烷氧基，氨基，单和二-C 1-2烷基氨基，和芳基和杂芳基的取代基取代 5至12名成员; R4选自氢; 基团 - （O）n -R 7，其中n为0或1，R 7为无环C 1-5烃基或具有3〜7个环成员的单环碳环或杂环基; 卤素; 氰基 羟基; 氨基; 和单 - 或二-C1-5烃基 - 氨基，其中无规C 1〜5烃基和单-C 1〜C 5烃基氨基部分任选被一个或多个选自羟基，卤素，C1 -2-烷氧基，氨基，单和二-C 1-2烷基氨基，以及5至12个环成员的芳基和杂芳基; 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R 5和R 6如权利要求中所定义。

公开(公告)号：US20120208791A1

公开(公告)日：2012-08-16

申请号：US12997754

申请日：2009-06-12

申请人： Valerio Berdini ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Martyn Frederickson ,  Charlotte Mary Griffiths-Jones ,  Christopher Charles Frederick Hamlett ,  Andrew Madin ,  Christopher William Murray ,  Rajdeep Kaur Benning ,  Gordon Saxty ,  Emma Vickerstaffe ,  Brian John Williams ,  Marian Williams ,  Andrew James Woodhead ,  Steven John Woodhead ,  Eddy Jean Edgard Freyne ,  Tom Cornelis Hortense Govaerts ,  Patrick René Angibaud

发明人： Valerio Berdini ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Martyn Frederickson ,  Charlotte Mary Griffiths-Jones ,  Christopher Charles Frederick Hamlett ,  Andrew Madin ,  Christopher William Murray ,  Rajdeep Kaur Benning ,  Gordon Saxty ,  Emma Vickerstaffe ,  Brian John Williams ,  Marian Williams ,  Andrew James Woodhead ,  Steven John Woodhead ,  Eddy Jean Edgard Freyne ,  Tom Cornelis Hortense Govaerts ,  Patrick René Angibaud

IPC分类号： A61K31/437 ,  A61K31/501 ,  A61P35/00 ,  C07D513/04 ,  A61K31/53 ,  A61K31/506 ,  C07D471/04 ,  A61K31/5377

CPC分类号： C07D471/04 ,  C07D513/04

摘要： The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及新的双环杂环衍生物化合物，包含所述化合物的药物组合物和所述化合物在治疗疾病中的用途。 癌症。

公开(公告)号：US08796244B2

公开(公告)日：2014-08-05

申请号：US12997754

申请日：2009-06-12

申请人： Valerio Berdini ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Martyn Frederickson ,  Charlotte Mary Griffiths-Jones ,  Christopher Charles Frederick Hamlett ,  Andrew Madin ,  Christopher William Murray ,  Rajdeep Kaur Benning ,  Gordon Saxty ,  Emma Vickerstaffe ,  Andrew James Woodhead ,  Steven John Woodhead ,  Eddy Jean Edgard Freyne ,  Tom Cornelis Hortense Govaerts ,  Patrick René Angibaud ,  Marian Williams

发明人： Valerio Berdini ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Martyn Frederickson ,  Charlotte Mary Griffiths-Jones ,  Christopher Charles Frederick Hamlett ,  Andrew Madin ,  Christopher William Murray ,  Rajdeep Kaur Benning ,  Gordon Saxty ,  Emma Vickerstaffe ,  Brian John Williams ,  Andrew James Woodhead ,  Steven John Woodhead ,  Eddy Jean Edgard Freyne ,  Tom Cornelis Hortense Govaerts ,  Patrick René Angibaud

IPC分类号： A61K31/5025 ,  C07D413/02

CPC分类号： C07D471/04 ,  C07D513/04

摘要： The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及新的双环杂环衍生物化合物，包含该化合物的药物组合物和该化合物在治疗疾病中的用途。 癌症。

公开(公告)号：US20090215777A1

公开(公告)日：2009-08-27

申请号：US11914728

申请日：2006-05-19

申请人： Gianni Chessari ,  Miles Stuart Congreve ,  Owen Callaghan ,  Suzanna Ruth Cowan ,  Christopher William Murray ,  Alison Jo-Anne Woolford ,  Michael Alistair O'Brien ,  Andrew James Woodhead

发明人： Gianni Chessari ,  Miles Stuart Congreve ,  Owen Callaghan ,  Suzanna Ruth Cowan ,  Christopher William Murray ,  Alison Jo-Anne Woolford ,  Michael Alistair O'Brien ,  Andrew James Woodhead

IPC分类号： A61K31/5377 ,  C07D239/42 ,  A61K31/505 ,  C07D413/12 ,  C07D251/42 ,  A61K31/53

CPC分类号： C07D413/04 ,  C07D239/42 ,  C07D239/47 ,  C07D239/48 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D409/04

摘要： The invention provides a compound for use as an inhibitor of Hsp90, the compound having the formula (I): or salts, tautomers, solvates or N-oxides thereof; wherein: A is N or a group CR3; R1 is a monocyclic or bicyclic carbocyclic or heterocyclic ring of 5 to 10 ring members of which up to two ring members may be heteroatoms selected from N, O and S and the remainder are carbon atoms, the carbocyclic or heterocyclic ring being optionally substituted by one or more substituent groups independently selected from R10; and R2, R3 and R10 are as defined in the claims.

摘要翻译： 本发明提供了用作Hsp90抑制剂的化合物，具有式（I）的化合物：或其盐，互变异构体，溶剂合物或N-氧化物; 其中：A为N或CR3基团; R 1是5至10个环成员的单环或双环碳环或杂环，其中多至两个环成员可以是选自N，O和S的杂原子，其余是碳原子，碳环或杂环任选被一个 或更多个独立地选自R 10的取代基; 并且R 2，R 3和R 10如权利要求中所定义。