公开(公告)号：US08524902B2

公开(公告)日：2013-09-03

申请号：US13253196

申请日：2011-10-05

Applicant: Jean-Damien Charrier ,  David Kay ,  Ronald Knegtel

Inventor： Jean-Damien Charrier ,  David Kay ,  Ronald Knegtel

IPC: C07D213/26

CPC classification number: C07D487/14

Abstract: The present invention relates to compounds useful as inhibitors of protein kinase, represented by Structural Formula (I): wherein the variables in Structural Formula (I) are as described herein. 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: 本发明涉及可用作结构式（I）表示的蛋白激酶抑制剂的化合物：其中结构式（I）中的变量如本文所述。 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：US08410112B2

公开(公告)日：2013-04-02

申请号：US13104291

申请日：2011-10-27

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

Inventor： Jean-Damien Charrier ,  Steven John Durrant ,  David Kay ,  Michael O'Donnell ,  Ronald Marcellus Alphonsus Knegtel ,  Somhairle MacCormick ,  Joanne Pinder ,  Stephen Clinton Young ,  Hayley 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: A61K31/4965 ,  C07D403/00

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US08399478B2

公开(公告)日：2013-03-19

申请号：US13033872

申请日：2011-02-24

Applicant: Guy Brenchley ,  Jean-Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegiel ,  Sharn Ramaya ,  Shazia Sadiq

Inventor： Guy Brenchley ,  Jean-Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegiel ,  Sharn Ramaya ,  Shazia Sadiq

IPC: A61K31/44

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: The present invention relates to compounds useful as inhibitors of protein kinase represented by formula (I): or a pharmaceutically acceptable salt thereof. 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: 本发明涉及可用作由式（I）表示的蛋白激酶抑制剂的化合物或其药学上可接受的盐。 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：US20130046544A1

公开(公告)日：2013-02-21

申请号：US13583840

申请日：2011-03-14

Applicant: David Kay ,  Pim Van Meurs ,  Erland Unruh ,  Santosh Sharan ,  Gordon Kessler ,  Mayank Agarwal ,  Greg Sigel

Inventor： David Kay ,  Pim Van Meurs ,  Erland Unruh ,  Santosh Sharan ,  Gordon Kessler ,  Mayank Agarwal ,  Greg Sigel

IPC: G06F3/02 ,  G10L11/00

CPC classification number: G06F3/023 ,  G06F3/0237 ,  G06F3/0481 ,  G06F3/04883 ,  G06F3/04886 ,  G06F17/2735 ,  G06F17/276 ,  G06F17/3064 ,  G06F2203/0381

Abstract: A system and method for entering text from a user includes a programmed processor that receives inputs from the user and disambiguates the inputs to present word choices corresponding to the text. In one embodiment, inputs are received in two or more modalities and are analyzed to present the word choices. In another embodiment, a keyboard is divided into zones each of which represents two more input characters. A sequence of zones selected by the user is analyzed to present word choices corresponding to the zone selected.

公开(公告)号：US20120277425A1

公开(公告)日：2012-11-01

申请号：US13253196

申请日：2011-10-05

Applicant: Jean-Damien Charrier ,  David Kay ,  Ronald Knegtel

Inventor： Jean-Damien Charrier ,  David Kay ,  Ronald Knegtel

IPC: C07D487/14

CPC classification number: C07D487/14

Abstract: 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.

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

Applicant: Jean-Damien Charrier ,  Steven Durrant ,  David Kay

Inventor： Jean-Damien Charrier ,  Steven Durrant ,  David Kay

IPC: C07D487/14

CPC classification number: C07D487/14

Abstract: 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).

Abstract translation: 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：US07855214B2

公开(公告)日：2010-12-21

申请号：US11046664

申请日：2005-01-26

Applicant: Juan-Miguel Jimenez ,  Sanjay Patel ,  David Kay ,  Ronald Knegtel ,  Oliver Philps

Inventor： Juan-Miguel Jimenez ,  Sanjay Patel ,  David Kay ,  Ronald Knegtel ,  Oliver Philps

IPC: C07D487/22 ,  C07D487/14 ,  A61K31/519 ,  A61P35/00 ,  A61P29/00

CPC classification number: C07D403/12 ,  C07D471/04 ,  C07D487/04 ,  C07D487/12

Abstract: The present invention relates to compounds useful as inhibitors of Tec family protein kinases. These compounds have the general formula I: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, G, Cy1, and X are as defined herein. 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.

Abstract translation: 本发明涉及可用作Tec家族蛋白激酶抑制剂的化合物。 这些化合物具有通式I或其药学上可接受的盐，其中R 1，R 2，R 3，R 4，R 5，G，Cy 1和X如本文所定义。 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：US20100222318A1

公开(公告)日：2010-09-02

申请号：US12642447

申请日：2009-12-18

Applicant: Jean Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegtel ,  Somhairle MacCormick ,  Michael Mortimore ,  Michael O'Donnell ,  Joanne Pinder ,  Alistair Rutherford ,  Anisa Nizarali Virani ,  Stephen Young ,  Philip Michael Reaper

Inventor： Jean Damien Charrier ,  Steven Durrant ,  David Kay ,  Ronald Knegtel ,  Somhairle MacCormick ,  Michael Mortimore ,  Michael O'Donnell ,  Joanne Pinder ,  Alistair Rutherford ,  Anisa Nizarali Virani ,  Stephen Young ,  Philip Michael Reaper

IPC: A61K31/497 ,  C12N5/02 ,  C07D413/14 ,  C07D413/04 ,  A61K31/5513 ,  C07D417/04 ,  A61K31/5377 ,  A61K31/553 ,  C07D403/10 ,  A61K35/04

CPC classification number: C07D413/14 ,  A61P35/00 ,  C07D241/28 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

Abstract: The present invention relates to pyrazine 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.

Abstract translation: 本发明涉及可用作ATR蛋白激酶抑制剂的吡嗪化合物。 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：US07691853B2

公开(公告)日：2010-04-06

申请号：US11369220

申请日：2006-03-06

Applicant: 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

Inventor： 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: C07D403/12 ,  C07D239/94 ,  A61K31/517 ,  A61K31/506 ,  A61P25/18 ,  A61P25/28

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20090221602A1

公开(公告)日：2009-09-03

申请号：US12436407

申请日：2009-05-06

Applicant: Jean-Damien Charrier ,  Francesca Mazzei ,  David Kay ,  Andrew Miller

Inventor： Jean-Damien Charrier ,  Francesca Mazzei ,  David Kay ,  Andrew Miller

IPC: A61K31/506 ,  C07D403/14 ,  C12N7/06 ,  A61P35/00

CPC classification number: C07D403/14 ,  C07D239/34 ,  C07D401/14 ,  C07D403/12 ,  C07D453/02

Abstract: The present invention provides a facile process for the preparation of tri- and tetra-substituted pyrimidines. The process is useful for preparing inhibitors of protein kinases, especially Aurora kinase. These inhibitors are useful for treating or lessening the severity of Aurora-mediated diseases or conditions.

Abstract translation: 本发明提供了制备三取代和四取代嘧啶的简便方法。 该方法可用于制备蛋白激酶抑制剂，特别是Aurora激酶。 这些抑制剂可用于治疗或减轻Aurora介导的疾病或病症的严重性。