公开(公告)号：US20120277425A1

公开(公告)日：2012-11-01

申请号：US13253196

申请日：2011-10-05

申请人： Jean-Damien Charrier ,  David Kay ,  Ronald Knegtel

发明人： Jean-Damien Charrier ,  David Kay ,  Ronald Knegtel

IPC分类号： C07D487/14

CPC分类号： C07D487/14

摘要： The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.

摘要翻译： 本发明涉及可用作蛋白激酶抑制剂的化合物。 本发明还提供包含所述化合物的药学上可接受的组合物和使用该组合物治疗各种疾病，病症或病症的方法。 本发明还提供了制备本发明化合物的方法。

公开(公告)号：US20120178926A1

公开(公告)日：2012-07-12

申请号：US13424736

申请日：2012-03-20

申请人： Jean-Damien Charrier ,  Steven Durrant ,  David Kay

发明人： Jean-Damien Charrier ,  Steven Durrant ,  David Kay

IPC分类号： C07D487/14

CPC分类号： C07D487/14

摘要： A method of preparing a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the variables of Structural Formula (I) are as described in the specification and claims, comprises the step of: a) cyclizing a compound represented by Structural Formula A: under suitable reductive cyclisation conditions to form a compound represented by Structural Formula B: wherein R10 is LG1 or —X1R1, and -LG1 is a suitable leaving group; and b) optionally, when R10 of Structural Formula (B) is LG1, further comprising the step of replacing the -LG1 of Structural Formula (B) with —X1R1 to form the compound represented by Structural Formula (I).

摘要翻译： 制备由结构式（I）表示的化合物或其药学上可接受的盐的方法，其中结构式（I）的变量如说明书和权利要求书中所述，包括以下步骤：a）使代表的化合物 通过结构式A：在合适的还原环化条件下，形成由结构式B表示的化合物：其中R10是LG1或-X1R1，-LG1是合适的离去基团; 和b）任选地，当结构式（B）的R 10是LG 1时，还包括用-X1R1替代结构式（B）的-LG1以形成由结构式（I）表示的化合物的步骤。

公开(公告)号：US20120077830A1

公开(公告)日：2012-03-29

申请号：US13309117

申请日：2011-12-01

申请人： Julian M.C. Golec ,  Paul S. Charifson ,  Jean-Damien Charrier ,  Hayley Binch

发明人： Julian M.C. Golec ,  Paul S. Charifson ,  Jean-Damien Charrier ,  Hayley Binch

IPC分类号： A61K31/517 ,  A61P29/00 ,  C07D239/80

CPC分类号： C07D209/48 ,  C07D209/46 ,  C07D213/64 ,  C07D215/227 ,  C07D217/24 ,  C07D239/36 ,  C07D239/80 ,  C07D239/88 ,  C07D239/90 ,  C07D471/04 ,  C07D495/04

摘要： This invention provides novel compounds, and pharmaceutically acceptable derivatives thereof, that are useful as caspase inhibitors. These compounds have the general formula I: where R1, R2, and R3 are as described herein, Ring A contains zero to two double bonds, each X is independently selected from nitrogen or carbon, at least one X in Ring A is a nitrogen, Ring A is optionally substituted as described, and may be fused to a saturated or unsaturated five to seven membered ring containing zero to three heteroatoms, and provided that when X3 is a carbon, a substituent on X3 is attached by an atom other than nitrogen.

摘要翻译： 本发明提供可用作半胱天冬酶抑制剂的新化合物及其药学上可接受的衍生物。 这些化合物具有通式I：其中R 1，R 2和R 3如本文所述，环A包含0至2个双键，每个X独立地选自氮或碳，环A中的至少一个X为氮， 环A如所述任选被取代，并且可以与含有0至3个杂原子的饱和或不饱和的5至7元环稠合，并且条件是当X 3是碳时，X 3上的取代基被除氮以外的原子连接。

公开(公告)号：US20120071657A1

公开(公告)日：2012-03-22

申请号：US13094183

申请日：2011-04-26

申请人： David Bebbington ,  Ronald Knegtel ,  Hayley Binch ,  Julian M.C. Golec ,  Pan Li ,  Jean-Damien Charrier

发明人： David Bebbington ,  Ronald Knegtel ,  Hayley Binch ,  Julian M.C. Golec ,  Pan Li ,  Jean-Damien Charrier

IPC分类号： C07D403/12 ,  C07D401/12

CPC分类号： C07D401/14 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D473/16 ,  C07D487/04 ,  C07D491/04 ,  C07D493/04 ,  C07D495/04 ,  C07D513/04

摘要： This invention describes novel triazole compounds of formula IX: wherein Z1 is nitrogen or CR9 and Z2 is nitrogen or CH, provided that at least one of Z1 and Z2 is nitrogen; G is Ring C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, wherein said Ring C has one or two ortho substituents independently selected from —R1; Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx and Ry are independently selected from T-R3, or Rx and Ry are taken together with their intervening atoms to form a fused ring; R1, R3, and T are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of GSK-3 and Aurora, for treating diseases such as diabetes, cancer, and Alzheimer's disease.

摘要翻译： 本发明描述了式IX的新型三唑化合物：其中Z1是氮或CR9，Z2是氮或CH，条件是Z1和Z2中的至少一个是氮; G是环C或环D; 环C选自苯基，吡啶基，嘧啶基，哒嗪基，吡嗪基或1,2,4-三嗪基，其中所述环C具有一个或两个独立地选自-R 1的邻位取代基; 环D是选自芳基，杂芳基，杂环基或碳环基的5-7元单环或8-10元双环; Rx和Ry独立地选自T-R3，或Rx和Ry与它们的插入原子一起形成稠环; R1，R3和T如说明书中所述。 这些化合物可用作蛋白激酶抑制剂，特别是作为GSK-3和Aurora的抑制剂，用于治疗诸如糖尿病，癌症和阿尔茨海默病的疾病。

公开(公告)号：US20120028966A1

公开(公告)日：2012-02-02

申请号：US12977197

申请日：2010-12-23

申请人： Jean-Damien Charrier ,  Steve Durrant

发明人： Jean-Damien Charrier ,  Steve Durrant

IPC分类号： A61K31/551 ,  C07D475/00 ,  C07D487/14 ,  A61K31/519 ,  C12N9/99 ,  A61P29/00 ,  A61P25/28 ,  A61P37/06 ,  A61P35/00 ,  A61P9/00 ,  A61P19/08 ,  A61P1/16 ,  A61P31/12 ,  A61P7/00 ,  A61P3/10 ,  A61P37/00 ,  A61P37/02 ,  A61P35/02 ,  C07D487/04

CPC分类号： C07D487/04

摘要： In one aspect, the invention provides compounds of Formula I or pharmaceutically acceptable salts thereof. In another aspect, the invention provides methods for treatment of diseases or disorders mediated by a protein kinase, comprising administering a therapeutically effective amount of a compound of this invention.

公开(公告)号：US20120010197A1

公开(公告)日：2012-01-12

申请号：US12977222

申请日：2010-12-23

申请人： Jean-Damien Charrier ,  Steven Durrant

发明人： Jean-Damien Charrier ,  Steven Durrant

IPC分类号： A61K31/551 ,  C07D475/00 ,  A61K31/519 ,  A61P25/28 ,  A61P37/00 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P7/00 ,  A61P3/10 ,  A61P31/12 ,  A61P9/00 ,  A61P37/06 ,  A61P37/02 ,  C12N9/99 ,  C07D487/04

CPC分类号： C07D487/04

摘要： In one aspect, the invention provides compounds of Formula I or pharmaceutically acceptable salts thereof. In another aspect, the invention provides methods for treatment of diseases or disorders mediated by a protein kinase, comprising administering a therapeutically effective amount of a compound of this invention.

公开(公告)号：US08093392B2

公开(公告)日：2012-01-10

申请号：US13022820

申请日：2011-02-08

申请人： Julian M. C. Golec ,  Paul S. Charifson ,  Jean-Damien Charrier ,  Hayley Marie Binch

发明人： Julian M. C. Golec ,  Paul S. Charifson ,  Jean-Damien Charrier ,  Hayley Marie Binch

IPC分类号： C07D215/38

CPC分类号： C07D209/48 ,  C07D209/46 ,  C07D213/64 ,  C07D215/227 ,  C07D217/24 ,  C07D239/36 ,  C07D239/80 ,  C07D239/88 ,  C07D239/90 ,  C07D471/04 ,  C07D495/04

摘要： This invention provides novel compounds, and pharmaceutically acceptable derivatives thereof, that are useful as caspase inhibitors. These compounds have the general formula I: where R1, R2, and R3 are as described herein, Ring A contains zero to two double bonds, each X is independently selected from nitrogen or carbon, at least one X in Ring A is a nitrogen, Ring A is optionally substituted as described, and may be fused to a saturated or unsaturated five to seven membered ring containing zero to three heteroatoms, and provided that when X3 is a carbon, a substituent on X3 is attached by an atom other than nitrogen.

公开(公告)号：US20110263575A1

公开(公告)日：2011-10-27

申请号：US12673287

申请日：2008-08-15

申请人： Francoise Pierard ,  Jean-Damien Charrier

发明人： Francoise Pierard ,  Jean-Damien Charrier

IPC分类号： A61K31/551 ,  C07D475/00 ,  A61K31/519 ,  A61P35/00 ,  A61P25/28 ,  A61P37/00 ,  A61P29/00 ,  A61P37/02 ,  A61P35/02 ,  A61P37/06 ,  A61P25/00 ,  A61P9/00 ,  A61P19/08 ,  A61P1/16 ,  A61P31/12 ,  A61P7/00 ,  A61P3/10 ,  C07D487/04

CPC分类号： C07D487/04 ,  A61K31/519 ,  A61K31/551 ,  A61K45/06 ,  C07D475/00 ,  C07D487/10 ,  C07D487/14

摘要： The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

摘要翻译： 本发明涉及可用作蛋白激酶抑制剂的化合物。 本发明还提供包含所述化合物的药学上可接受的组合物和使用该组合物治疗各种疾病，病症或病症的方法。

公开(公告)号：US20110144074A1

公开(公告)日：2011-06-16

申请号：US13012180

申请日：2011-01-24

申请人： Michael Mortimore ,  Andrew Miller ,  John Studley ,  Jean-Damien Charrier

发明人： Michael Mortimore ,  Andrew Miller ,  John Studley ,  Jean-Damien Charrier

IPC分类号： A61K31/58 ,  A61K31/405 ,  A61K31/5415 ,  A61K31/473 ,  A61K31/55 ,  A61K31/496 ,  A61K31/437 ,  A61K31/5025 ,  A61K31/538 ,  A61K31/498 ,  A61K31/45 ,  A61K31/4015 ,  A61P29/00 ,  A61P31/00 ,  A61P19/02 ,  A61P3/10 ,  A61P37/06 ,  A61P35/00 ,  A61P25/28 ,  A01N1/02 ,  C12N5/071

CPC分类号： A61K31/55 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/407 ,  A61K31/435 ,  A61K31/45 ,  A61K31/498 ,  A61K31/5025 ,  A61K31/538 ,  A61K31/54 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389

摘要： This invention provides caspase inhibitors of formula I: wherein Z is oxygen or sulfur; R1 is hydrogen, —CHN2, R, CH2OR, CH2SR, or —CH2Y; between R3 and R4 represents a single or double bond; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R3 is a group capable of fitting into the S2 subsite of a caspase enzyme; R4 is a hydrogen or C1-6 alkyl or R3 and R4 taken together form a ring; Ring A and Ring B are each heterocyclic rings, and R and R5 are as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1β secretion.

摘要翻译： 本发明提供了式I的半胱天冬酶抑制剂：其中Z是氧或硫; R1是氢，-CHN2，R，CH2OR，CH2SR或-CH2Y; R3和R4之间代表单键或双键; Y是电负离子团; R2是CO 2 H，CH 2 CO 2 H或其酯，酰胺或等体积体; R3是能够适应胱天蛋白酶的S2亚位点的基团; R4是氢或C1-6烷基或R3和R4一起形成环; 环A和环B各自为杂环，R和R 5如说明书所述。 这些化合物是有效的凋亡抑制剂和IL-1和bgr; 分泌。

公开(公告)号：US07691853B2

公开(公告)日：2010-04-06

申请号：US11369220

申请日：2006-03-06

申请人： David Bebbington ,  Hayley Binch ,  Ronald Knegtel ,  Julian M. C. Golec ,  Sanjay Patel ,  Jean-Damien Charrier ,  David Kay ,  Robert J. Davies ,  Pan Li ,  Marion W. Wannamaker ,  Cornelia J. Forster ,  Albert C. Pierce

发明人： David Bebbington ,  Hayley Binch ,  Ronald Knegtel ,  Julian M. C. Golec ,  Sanjay Patel ,  Jean-Damien Charrier ,  David Kay ,  Robert J. Davies ,  Pan Li ,  Marion W. Wannamaker ,  Cornelia J. Forster ,  Albert C. Pierce

IPC分类号： C07D403/12 ,  C07D239/94 ,  A61K31/517 ,  A61K31/506 ,  A61P25/18 ,  A61P25/28

CPC分类号： C07D401/14 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D473/16 ,  C07D487/04 ,  C07D491/04 ,  C07D491/10 ,  C07D493/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04

摘要： This invention describes novel pyrazole compounds of formula IV: wherein Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx and Ry are independently selected from T—R3, or taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5-8 membered ring having 1-3 ring heteroatoms selected from oxygen, sulfur, or nitrogen; and R2, R2′, T, and R3 are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of aurora-2 and GSK-3, for treating diseases such as cancer, diabetes and Alzheimer's disease.

摘要翻译： 本发明描述了式IV的新型吡唑化合物：其中环D是5-7元单环或选自芳基，杂芳基，杂环基或碳环基的8-10元双环; R x和R y独立地选自T-R 3，或与它们的插入原子一起形成具有1-3个选自氧，硫或氮的环杂原子的稠合的，不饱和的或部分不饱和的5-8元环; R2，R2'，T和R3如说明书中所述。 这些化合物可用作蛋白激酶抑制剂，特别是作为用于治疗诸如癌症，糖尿病和阿尔茨海默病的疾病的极光-2和GSK-3的抑制剂。