公开(公告)号：WO2007056221A2

公开(公告)日：2007-05-18

申请号：PCT/US2006043096

申请日：2006-11-03

Applicant: VERTEX PHARMA ,  BINCH HAYLEY ,  MORTIMORE MICHAEL ,  DAVIS CHRIS ,  BOYALL DEAN ,  EVERITT SIMON ,  ROBINSON DANIEL ,  RAMAYA SHARN ,  FRAYSSE DAMIEN ,  STUDLEY JOHN ,  MILIER ANDREW ,  O'DONNELL MICHAEL ,  RUTHERFORD ALISTAIR ,  PINDER JOANNE

Inventor： BINCH HAYLEY ,  MORTIMORE MICHAEL ,  DAVIS CHRIS ,  BOYALL DEAN ,  EVERITT SIMON ,  ROBINSON DANIEL ,  RAMAYA SHARN ,  FRAYSSE DAMIEN ,  STUDLEY JOHN ,  MILIER ANDREW ,  O'DONNELL MICHAEL ,  RUTHERFORD ALISTAIR ,  PINDER JOANNE

IPC: A61K31/513

CPC classification number: C07D403/12 ,  C07D239/38 ,  C07D401/14 ,  C07D403/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

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

Abstract translation: 本发明涉及可用作蛋白激酶抑制剂的化合物。 本发明还提供包含这些化合物的药学上可接受的组合物和使用该化合物和组合物治疗各种疾病，病症和障碍的方法。 本发明还提供了制备本发明化合物的方法。

公开(公告)号：WO02094263A3

公开(公告)日：2003-03-27

申请号：PCT/US0216353

申请日：2002-05-23

Applicant: VERTEX PHARMA ,  MORTIMORE MICHAEL ,  MILLER ANDREW ,  STUDLEY JOHN ,  CHARRIER JEAN-DAMIEN

Inventor： MORTIMORE MICHAEL ,  MILLER ANDREW ,  STUDLEY JOHN ,  CHARRIER JEAN-DAMIEN

IPC: A61K31/404 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/407 ,  A61K31/435 ,  A61K31/45 ,  A61K31/498 ,  A61K31/5025 ,  A61K31/538 ,  A61K31/54 ,  A61K31/55 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P1/18 ,  A61P3/00 ,  A61P3/10 ,  A61P7/00 ,  A61P7/06 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P13/00 ,  A61P13/12 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P19/08 ,  A61P19/10 ,  A61P21/00 ,  A61P21/04 ,  A61P25/00 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P27/00 ,  A61P29/00 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P39/02 ,  A61P43/00 ,  C07D209/86

CPC classification number: A61K31/55 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/407 ,  A61K31/435 ,  A61K31/45 ,  A61K31/498 ,  A61K31/5025 ,  A61K31/538 ,  A61K31/54

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

Abstract translation: 本发明提供式（I）化合物：其中Z是氧或磺基; R 1是氢，-CHN 2，R 1，CH 2 OR，CH 2 SR或-CH 2 Y; --- R 3独立表示单键或双键; Y是电负离子团; R 2是CO 2 H，CH 2 CO 2 H或其酯，酰胺或等体异构体; R 3是能够适合S2亚位点或胱天蛋白酶的基团; R 4是氢或C 1-6烷基或R 3和R 4一起形成环; 环A和环B各自为杂环，R和R 5如说明书所述。 这些化合物是凋亡和IL-1β分泌的有效抑制剂。

公开(公告)号：WO2008115973A3

公开(公告)日：2008-12-04

申请号：PCT/US2008057465

申请日：2008-03-19

Applicant: VERTEX PHARMA ,  BINCH HAYLEY ,  YOUNG STEPHEN ,  DAVIS CHRISTOPHER ,  MORTIMORE MICHAEL ,  GOLEC JULIAN ,  STUDLEY JOHN ,  ROBINSON DANIEL ,  O'DONNELL MICHAEL ,  BOYALL DEAN ,  PINDER JOANNE ,  EVERITT SIMON

Inventor： BINCH HAYLEY ,  YOUNG STEPHEN ,  DAVIS CHRISTOPHER ,  MORTIMORE MICHAEL ,  GOLEC JULIAN ,  STUDLEY JOHN ,  ROBINSON DANIEL ,  O'DONNELL MICHAEL ,  BOYALL DEAN ,  PINDER JOANNE ,  EVERITT SIMON

IPC: C07D403/14 ,  A61K31/33 ,  A61K35/00 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

CPC classification number: C07D471/04 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to compounds useful as inhibitors of Aurora protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

公开(公告)号：WO0172707A3

公开(公告)日：2002-05-23

申请号：PCT/US0110182

申请日：2001-03-29

Applicant: VERTEX PHARMA ,  BEBBINGTON DAVID ,  CHARRIER JEAN DAMIEN ,  KAY DAVID ,  KNEGTEL RONALD ,  GOLEC JULIAN ,  MORTIMORE MICHAEL ,  STUDLEY JOHN

Inventor： BEBBINGTON DAVID ,  CHARRIER JEAN-DAMIEN ,  KAY DAVID ,  KNEGTEL RONALD ,  GOLEC JULIAN ,  MORTIMORE MICHAEL ,  STUDLEY JOHN

IPC: A61K31/403 ,  A61K31/404 ,  A61K31/473 ,  A61K31/496 ,  A61K31/5415 ,  A61K31/55 ,  A61K31/575 ,  A61P9/00 ,  A61P19/02 ,  A61P19/08 ,  A61P25/32 ,  A61P29/00 ,  A61P31/04 ,  A61P31/12 ,  A61P35/00 ,  A61P37/06 ,  A61P43/00 ,  C07D209/04 ,  C07D209/08 ,  C07D209/82 ,  C07D209/86 ,  C07D221/12 ,  C07D223/22 ,  C07D223/26 ,  C07D223/28 ,  C07D279/30 ,  C07D279/36 ,  C07D403/12 ,  C07J9/00 ,  A61K31/395 ,  C07D209/88

CPC classification number: C07D403/12 ,  C07D209/08 ,  C07D209/86 ,  C07D221/12 ,  C07D223/26 ,  C07D223/28 ,  C07D279/30

Abstract: This invention provides caspase inhibitors of formula (I): wherein Z is oxygen or sulfur; R is hydrogen, -CHN2,R, CH2OR, CH2SR, or -CH2Y; Y is an electronegative leaving group; R is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R is a group capable of fitting into the S2 subsite of a caspase enzyme; R and R are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1 beta secretion.

Abstract translation: 本发明提供了式（I）的半胱天冬酶抑制剂：其中Z是氧或硫; R 1是氢，-CHN 2，R 1，CH 2 OR，CH 2 SR或-CH 2 Y; Y是电负离子团; R 2是CO 2 H，CH 2 CO 2 H或其酯，酰胺或等体积体; R 3是能够适应半胱天冬酶的S2亚位点的基团; R 4和R 5与中间的氮一起形成杂环，R如说明书中所述。 这些化合物是凋亡和IL-1β分泌的有效抑制剂。

公开(公告)号：WO2013049726A2

公开(公告)日：2013-04-04

申请号：PCT/US2012058127

申请日：2012-09-28

Applicant: VERTEX PHARMA ,  CHARRIER JEAN-DAMIEN ,  STUDLEY JOHN ,  PIERARD FRANCOISE YVONNE THEODORA MARIE ,  DURRANT STEVEN JOHN ,  LITTLER BENJAMIN JOSEPH ,  HUGHES ROBERT MICHAEL ,  SIESEL DAVID ANDREW ,  ANGELL PAUL ,  URBINA ARMANDO ,  SHI YI

Inventor： CHARRIER JEAN-DAMIEN ,  STUDLEY JOHN ,  PIERARD FRANCOISE YVONNE THEODORA MARIE ,  DURRANT STEVEN JOHN ,  LITTLER BENJAMIN JOSEPH ,  HUGHES ROBERT MICHAEL ,  SIESEL DAVID ANDREW ,  ANGELL PAUL ,  URBINA ARMANDO ,  SHI YI

IPC: C07D413/04 ,  A61K31/497 ,  A61P35/00

CPC classification number: C07D413/04 ,  C07C251/48 ,  C07D241/20 ,  C07D413/14

Abstract: The present invention relates to processes and intermediates for preparing compounds useful as inhibitors of ATR kinase, such as aminopyrazine-isoxazole derivatives and related molecules. The present invention also relates to compounds useful as inhibitors of ATR protein kinase. The invention relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and solid forms of the compounds of this invention. The compounds of this invention have formula (I) or (II) wherein the variables are as defined herein.

Abstract translation: 本发明涉及制备用作ATR激酶抑制剂的化合物的方法和中间体，例如氨基吡嗪 - 异恶唑衍生物和相关分子。 本发明还涉及可用作ATR蛋白激酶抑制剂的化合物。 本发明涉及包含本发明化合物的药学上可接受的组合物; 使用本发明化合物治疗各种疾病，病症和病症的方法; 制备本发明化合物的方法; 用于制备本发明化合物的中间体; 和本发明化合物的固体形式。 本发明的化合物具有式（I）或（II），其中变量如本文所定义。

公开(公告)号：WO2010011772A3

公开(公告)日：2010-04-29

申请号：PCT/US2009051437

申请日：2009-07-22

Applicant: VERTEX PHARMA ,  JIMENEZ JUAN-MIGUEL ,  STUDLEY JOHN

Inventor： JIMENEZ JUAN-MIGUEL ,  STUDLEY JOHN

IPC: C07D471/04 ,  A61K31/437 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00

CPC classification number: C07D471/04

Abstract: The present invention relates to compounds Formula (I) which are 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.

Abstract translation: 本发明涉及可用作蛋白激酶抑制剂的式（I）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：WO2008137619A2

公开(公告)日：2008-11-13

申请号：PCT/US2008062327

申请日：2008-05-02

Applicant: VERTEX PHARMA ,  STUDLEY JOHN ,  GOLEC JULIAN ,  DAVIS CHRISTOPHER ,  MORTIMORE MICHAEL ,  ROBINSON DANIEL

Inventor： STUDLEY JOHN ,  GOLEC JULIAN ,  DAVIS CHRISTOPHER ,  MORTIMORE MICHAEL ,  ROBINSON DANIEL

IPC: C07D417/14 ,  A61K31/4535

CPC classification number: C07D417/14 ,  C07D401/14

Abstract: The present invention relates to compounds useful as inhibitors of Aurora protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

Abstract translation: 本发明涉及可用作Aurora蛋白激酶抑制剂的化合物。 本发明还提供包含这些化合物的药学上可接受的组合物和使用该化合物和组合物治疗各种疾病，病症和障碍的方法。 本发明还提供了制备本发明化合物的方法。

公开(公告)号：WO2008128009A2

公开(公告)日：2008-10-23

申请号：PCT/US2008059975

申请日：2008-04-11

Applicant: VERTEX PHARMA ,  BINCH HAYLEY ,  YOUNG STEPHEN ,  DAVIS CHRISTOPHER ,  MORTIMORE MICHAEL ,  GOLEC JULIAN ,  STUDLEY JOHN ,  ROBINSON DANIEL ,  JIMENEZ JUAN-MIGUEL

Inventor： BINCH HAYLEY ,  YOUNG STEPHEN ,  DAVIS CHRISTOPHER ,  MORTIMORE MICHAEL ,  GOLEC JULIAN ,  STUDLEY JOHN ,  ROBINSON DANIEL ,  JIMENEZ JUAN-MIGUEL

IPC: C07D403/14 ,  A61K31/506 ,  A61P35/00

CPC classification number: C07D403/14 ,  C07D401/14 ,  C07D471/04

Abstract: The present invention relates to compounds useful as inhibitors of Aurora protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

Abstract translation: 本发明涉及用作极光蛋白激酶抑制剂的化合物。 本发明还提供包含这些化合物的药学上可接受的组合物以及使用该化合物和组合物治疗各种疾病，病症和障碍的方法。 本发明还提供了制备本发明化合物的方法。

公开(公告)号：WO2015187451A9

公开(公告)日：2016-05-19

申请号：PCT/US2015032879

申请日：2015-05-28

Applicant: VERTEX PHARMA

Inventor： AHMAD NADIA ,  CHARRIER JEAN-DAMIEN ,  DAVIS CHRIS ,  ETXEBARRIA I JARDI GORKA ,  FRAYSSE DAMIEN ,  KNEGTEL RONALD ,  PANESAR MANINDER ,  PIERARD FRANCOISE ,  PINDER JOANNE ,  STORCK PIERRE-HENRI ,  STUDLEY JOHN

IPC: C07D487/04

CPC classification number: C07D487/04

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and solid forms of the compounds of this invention. The compounds of this invention have formula (I-l) or (I-A); wherein the variables are as defined herein.

Abstract translation: 本发明涉及可用作ATR蛋白激酶抑制剂的化合物。 本发明涉及包含本发明化合物的药学上可接受的组合物; 使用本发明化合物治疗各种疾病，病症和病症的方法; 制备本发明化合物的方法; 用于制备本发明化合物的中间体; 和本发明化合物的固体形式。 本发明化合物具有式（I-1）或（I-A）; 其中变量如本文所定义。

公开(公告)号：WO2014089379A1

公开(公告)日：2014-06-12

申请号：PCT/US2013073457

申请日：2013-12-06

Applicant: VERTEX PHARMA

Inventor： AHMAD NADIA ,  BOYALL DEAN ,  CHARRIER JEAN-DAMIEN ,  DAVIS CHRIS ,  DAVIS REBECCA ,  DURRANT STEVEN ,  ETXEBARRIA I JARDI GORKA ,  FRAYSSE DAMIEN ,  JIMENEZ JUAN-MIGUEL ,  KAY DAVID ,  KNEGTEL RONALD ,  MIDDLETON DONALD ,  ODONNELL MICHAEL ,  PANESAR MANINDER ,  PIERARD FRANCOISE ,  PINDER JOANNE ,  SHAW DAVID ,  STORCK PIERRE-HENRI ,  STUDLEY JOHN ,  TWIN HEATHER

IPC: C07D487/04 ,  A61K31/495 ,  A61P35/00

CPC classification number: C07D487/04 ,  C07D453/02 ,  C07D471/08 ,  C07D487/08 ,  C07D491/107 ,  C07D498/04 ,  C07D498/10

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula (I) or a pharmaceutically acceptable salt, wherein the variables are as devined herein. Moreover, The compounds of this invention have formula (I-A) or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

Abstract translation: 本发明涉及可用作ATR蛋白激酶抑制剂的化合物。 本发明还涉及包含本发明化合物的药学上可接受的组合物; 使用本发明化合物治疗各种疾病，病症和病症的方法; 制备本发明化合物的方法; 用于制备本发明化合物的中间体; 以及在体外应用中使用化合物的方法，如生物和病理现象中激酶的研究; 由这种激酶介导的细胞内信号转导途径的研究; 和新型激酶抑制剂的比较评估。 本发明的化合物具有式（I）或其药学上可接受的盐，其中变量如本文所述。 此外，本发明的化合物具有式（I-A）或其药学上可接受的盐，其中变量如本文所定义。