公开(公告)号：US09062008B2

公开(公告)日：2015-06-23

申请号：US13106337

申请日：2011-05-12

申请人： Jean-Damien Charrier ,  Steven John Durrant ,  Stephen Clinton Young ,  Pierre-Henri Storck ,  Anisa Nizarali Virani ,  Philip Michael Reaper ,  Joanne Pinder

发明人： Jean-Damien Charrier ,  Steven John Durrant ,  Stephen Clinton Young ,  Pierre-Henri Storck ,  Anisa Nizarali Virani ,  Philip Michael Reaper ,  Joanne Pinder

IPC分类号： A61K31/497 ,  A61K31/4965 ,  C07D241/20 ,  C07D401/04 ,  C07D403/04

CPC分类号： C07D241/20 ,  C07D401/04 ,  C07D403/04

摘要： The present invention relates to pyrazine and pyridine 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 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 V: wherein the variables are as defined herein.

摘要翻译： 本发明涉及可用作ATR蛋白激酶抑制剂的吡嗪和吡啶化合物。 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V：其中变量如本文所定义。

公开(公告)号：US08877759B2

公开(公告)日：2014-11-04

申请号：US13440981

申请日：2012-09-04

申请人： Jean-Damien Charrier ,  David Kay ,  Somhairle MacCormick ,  Pierre-Henri Storck ,  Joanne Pinder ,  Michael Edward O'Donnell ,  Ronald Marcellus Alphonsus Knegtel ,  Stephen Clinton Young ,  Philip Michael Reaper ,  Steven John Durrant ,  Heather Clare Twin ,  Christopher John Davis

发明人： Jean-Damien Charrier ,  David Kay ,  Somhairle MacCormick ,  Pierre-Henri Storck ,  Joanne Pinder ,  Michael Edward O'Donnell ,  Ronald Marcellus Alphonsus Knegtel ,  Stephen Clinton Young ,  Philip Michael Reaper ,  Steven John Durrant ,  Heather Clare Twin ,  Christopher John Davis

IPC分类号： A61K31/4965 ,  C07D403/00 ,  A61K31/501 ,  A61K45/06 ,  A61K31/55 ,  A61K31/5377 ,  A61K31/7068 ,  C07D413/14 ,  C07D495/04 ,  A61K31/7048 ,  A61K33/24 ,  A61K31/497 ,  C07D453/00

CPC分类号： C07D413/14 ,  A61K31/497 ,  A61K31/501 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/555 ,  A61K31/7048 ,  A61K31/7068 ,  A61K33/24 ,  A61K45/06 ,  C07D453/00 ,  C07D453/02 ,  C07D495/04 ,  A61K2300/00

摘要： 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: wherein the variables are as defined herein.

摘要翻译： 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：其中变量如本文所定义。

公开(公告)号：US08530489B2

公开(公告)日：2013-09-10

申请号：US13477663

申请日：2012-05-22

申请人： Michael Mortimore ,  Stephen Clinton Young ,  Simon Robert Lorrie Everitt ,  Ronald Knegtel ,  Joanne Louise Pinder ,  Alistair Peter Rutherford ,  Steven Durrant ,  Guy Brenchley ,  Jean-Damien Charrier ,  Michael O'Donnell

发明人： Michael Mortimore ,  Stephen Clinton Young ,  Simon Robert Lorrie Everitt ,  Ronald Knegtel ,  Joanne Louise Pinder ,  Alistair Peter Rutherford ,  Steven Durrant ,  Guy Brenchley ,  Jean-Damien Charrier ,  Michael O'Donnell

IPC分类号： A01N43/54 ,  A61K31/505

CPC分类号： C07D471/04

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：US20130089624A1

公开(公告)日：2013-04-11

申请号：US13631730

申请日：2012-09-28

申请人： Jean-Damien Charrier ,  Stephen Clinton Young ,  Christopher John Davis ,  John Studley

发明人： Jean-Damien Charrier ,  Stephen Clinton Young ,  Christopher John Davis ,  John Studley

IPC分类号： C07D413/14 ,  A61K33/24 ,  C07D267/10 ,  C07D413/10 ,  C07D413/04 ,  A61K31/5377 ,  C07D265/30

CPC分类号： A61K31/5377 ,  A61K33/24 ,  C07D265/30 ,  C07D267/10 ,  C07D401/04 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14

摘要： 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: wherein the variables are as defined herein.Additionally, the present invention also relates to novel processes for the production of various morpoholine based intermediates.

摘要翻译： 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：其中变量如本文所定义。 此外，本发明还涉及用于生产各种基于morpoholine的中间体的新方法。

公开(公告)号：US08394952B2

公开(公告)日：2013-03-12

申请号：US13206638

申请日：2011-08-10

申请人： David Kay ,  Ronald Knetgel ,  Jean-Damien Charrier ,  Heather Twin

发明人： David Kay ,  Ronald Knetgel ,  Jean-Damien Charrier ,  Heather Twin

IPC分类号： C07D401/12

CPC分类号： C07D487/04 ,  A61K31/551 ,  A61K45/06 ,  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.

公开(公告)号：US20130034616A1

公开(公告)日：2013-02-07

申请号：US13531467

申请日：2012-06-22

申请人： Pierre-Henri Storck ,  Jean-Damien Charrier ,  Alistair Rutherford ,  Michael Paul Mortimore ,  Somhairle MacCormick ,  Ronald Marcellus Alphonsus Knegtel ,  Steven John Durrant

发明人： Pierre-Henri Storck ,  Jean-Damien Charrier ,  Alistair Rutherford ,  Michael Paul Mortimore ,  Somhairle MacCormick ,  Ronald Marcellus Alphonsus Knegtel ,  Steven John Durrant

IPC分类号： A61K31/4985 ,  A61K31/5377 ,  A61K31/7048 ,  A61K33/24 ,  A61P35/00 ,  C07D487/04 ,  A61K31/551

CPC分类号： C07D487/04

摘要： The present invention relates to pyrrolopyrazines 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: wherein the variables are as defined herein.

公开(公告)号：US20120309963A1

公开(公告)日：2012-12-06

申请号：US13477663

申请日：2012-05-22

申请人： Michael Mortimore ,  Stephen Clinton Young ,  Simon Robert Lorrie Everitt ,  Ronald Knegtel ,  Joanne Louise Pinder ,  Alistair Peter Rutherford ,  Steven Durrant ,  Guy Brenchley ,  Jean-Damien Charrier ,  Michael O'Donnell

发明人： Michael Mortimore ,  Stephen Clinton Young ,  Simon Robert Lorrie Everitt ,  Ronald Knegtel ,  Joanne Louise Pinder ,  Alistair Peter Rutherford ,  Steven Durrant ,  Guy Brenchley ,  Jean-Damien Charrier ,  Michael O'Donnell

IPC分类号： C07D471/04

CPC分类号： C07D471/04

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：US08304414B2

公开(公告)日：2012-11-06

申请号：US12109598

申请日：2008-04-25

申请人： David Bebbington ,  Jean-Damien Charrier ,  Julian Golec ,  Françoise Pierard

发明人： David Bebbington ,  Jean-Damien Charrier ,  Julian Golec ,  Françoise Pierard

IPC分类号： A61K31/50 ,  A61K31/501 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D409/00

CPC分类号： C07D403/14 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  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 pyrazole compounds of formula III: wherein Z1, Z2, and Z3 are as described in the specification; Q is —S—, —O—, —N(R4)—, or —CH(R6)—; R1 is T-Ring D, wherein Ring D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; and R2 and R2′ 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III的新型吡唑化合物：其中Z1，Z2和Z3如说明书所述; Q是-S - ， - O - ， - N（R4） - 或-CH（R6） - ; R1是T环D，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; R2和R2'如说明书所述。 这些化合物可用作蛋白激酶抑制剂，特别是作为Aurora-2和GSK-3的抑制剂用于治疗诸如癌症，糖尿病和阿尔茨海默病的疾病。

公开(公告)号：US08188281B2

公开(公告)日：2012-05-29

申请号：US12273799

申请日：2008-11-19

申请人： Francesco Salituro ,  Luc Farmer ,  Randy Bethiel ,  Edmund Harrington ,  Jeremy Green ,  John Court ,  Jon Come ,  David Lauffer ,  Alex Aronov ,  Hayley Binch ,  Dean Boyall ,  Jean-Damien Charrier ,  Simon Everitt ,  Damien Fraysse ,  Michael Mortimore ,  Francoise Pierard ,  Daniel Robinson ,  Jian Wang ,  Joanne Pinder ,  Tiansheng Wang ,  Albert Pierce

发明人： Francesco Salituro ,  Luc Farmer ,  Randy Bethiel ,  Edmund Harrington ,  Jeremy Green ,  John Court ,  Jon Come ,  David Lauffer ,  Alex Aronov ,  Hayley Binch ,  Dean Boyall ,  Jean-Damien Charrier ,  Simon Everitt ,  Damien Fraysse ,  Michael Mortimore ,  Francoise Pierard ,  Daniel Robinson ,  Jian Wang ,  Joanne Pinder ,  Tiansheng Wang ,  Albert Pierce

IPC分类号： C07D471/02

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61K31/551 ,  A61K31/695 ,  A61K45/06 ,  C07D519/00 ,  C07F7/0805

摘要： The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

摘要翻译： 本发明涉及蛋白激酶抑制剂。 本发明还提供包含本发明化合物的药物组合物和使用该组合物治疗各种疾病的方法。

公开(公告)号：US20120040020A1

公开(公告)日：2012-02-16

申请号：US13104291

申请日：2011-10-27

申请人： Jean-Damien Charrier ,  Steven John Durrant ,  David Kay ,  Michael O'Donnell ,  Ronald Marcellus Alphonsus Knegtel ,  Somhairle MacCormick ,  Joanne Pinder ,  Stephen Clinton Young ,  Haley Marie Binch ,  Thomas Cleveland ,  Lev Tyler Dewey Fanning ,  Dennis James Hurley ,  Pramod Joshi ,  Urvi Jagdishbhai Sheth ,  Alina Silina ,  Philip Michael Reaper ,  Anisa Nizarali Virani

发明人： Jean-Damien Charrier ,  Steven John Durrant ,  David Kay ,  Michael O'Donnell ,  Ronald Marcellus Alphonsus Knegtel ,  Somhairle MacCormick ,  Joanne Pinder ,  Stephen Clinton Young ,  Haley Marie Binch ,  Thomas Cleveland ,  Lev Tyler Dewey Fanning ,  Dennis James Hurley ,  Pramod Joshi ,  Urvi Jagdishbhai Sheth ,  Alina Silina ,  Philip Michael Reaper ,  Anisa Nizarali Virani

IPC分类号： A61K33/24 ,  C07D401/14 ,  C07D413/14 ,  A61K31/551 ,  A61K31/497 ,  A61K31/5377 ,  C07D417/14 ,  A61K31/541 ,  C07D405/14 ,  C07D471/04 ,  C07D491/113 ,  A61K31/506 ,  C07D513/04 ,  C07D409/14 ,  C07D487/04 ,  A61K31/4985 ,  C07D487/10 ,  A61K38/16 ,  A61K31/704 ,  A61K31/675 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/706 ,  A61K38/12 ,  A61P17/06 ,  A61P35/00 ,  A61P31/18 ,  A61P1/16 ,  A61P31/20 ,  C07D403/14

CPC分类号： C07D403/14 ,  A61K31/497 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07D241/28 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D487/10 ,  C07D491/113

摘要： The present disclosure relates to pyrazine compounds of formula I: wherein L, n, R1, and R2 are as described in the specification. These compounds are useful as inhibitors of ATR protein kinase. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of the disclosure; methods of treating of various diseases, disorders, and conditions using the compounds of the disclosure; processes for preparing the compounds of the disclosure; intermediates for the preparation of the compounds of the disclosure; 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.

摘要翻译： 本公开涉及式I的吡嗪化合物：其中L，n，R 1和R 2如说明书中所述。 这些化合物可用作ATR蛋白激酶的抑制剂。 本公开还涉及包含本公开内容的化合物的药学上可接受的组合物; 使用本公开的化合物治疗各种疾病，病症和病症的方法; 制备本公开的化合物的方法; 用于制备本公开的化合物的中间体; 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。