公开(公告)号：US08648066B2

公开(公告)日：2014-02-11

申请号：US12784254

申请日：2010-05-20

Applicant: Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Chris Allen Buhr ,  Joerg Bussenius ,  Jeffry Kimo Curtis ,  Steven Charles DeFina ,  Larisa Dubenko ,  Jason R. Harris ,  Eileen E. Jackson-Ugueto ,  Anagha Joshi ,  Angie Inyoung Kim ,  Amy Lew Tsuhako ,  Sunghoon Ma ,  Jean-Claire Limun Manalo ,  Stephanie Ng ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang ,  Cristiana A. Zaharia

Inventor： Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Chris Allen Buhr ,  Joerg Bussenius ,  Jeffry Kimo Curtis ,  Steven Charles DeFina ,  Larisa Dubenko ,  Jason R. Harris ,  Eileen E. Jackson-Ugueto ,  Anagha Joshi ,  Angie Inyoung Kim ,  Amy Lew Tsuhako ,  Sunghoon Ma ,  Jean-Claire Limun Manalo ,  Stephanie Ng ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang ,  Cristiana A. Zaharia

IPC: A61P35/00 ,  A61K31/553 ,  C07D267/14

CPC classification number: C07D413/14 ,  C07D413/04 ,  C07D417/14 ,  C07D471/04 ,  C07D471/14 ,  C07D487/04 ,  C07D487/08 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  C07D519/00

Abstract: The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

Abstract translation: 本发明涉及式I化合物及其药学上可接受的盐或溶剂合物，以及制备和使用该化合物的方法。

公开(公告)号：US07704995B2

公开(公告)日：2010-04-27

申请号：US10513081

申请日：2003-05-02

Applicant: Chris A. Buhr ,  Tae-Gon Baik ,  Sunghoon Ma ,  Zerom Tesfai ,  Longcheng Wang ,  Erick Wang Co ,  Sergey Epshteyn ,  Abigail R Kennedy ,  Baili Chen ,  Larisa Dubenko ,  Neel Kumar Anand ,  Tsze H. Tsang ,  John M. Nuss ,  Csaba J Peto ,  Kenneth D. Rice ,  Mohamed Abdulkader Ibrahim ,  Kevin Luke Schnepp ,  Xian Shi ,  James William Leahy ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Grace Mann ,  Larry Wayne Mann ,  Craig Stacy Takeuchi ,  Peter Lamb ,  David J. Matthews ,  Nicole Miller

Inventor： Chris A. Buhr ,  Tae-Gon Baik ,  Sunghoon Ma ,  Zerom Tesfai ,  Longcheng Wang ,  Erick Wang Co ,  Sergey Epshteyn ,  Abigail R Kennedy ,  Baili Chen ,  Larisa Dubenko ,  Neel Kumar Anand ,  Tsze H. Tsang ,  John M. Nuss ,  Csaba J Peto ,  Kenneth D. Rice ,  Mohamed Abdulkader Ibrahim ,  Kevin Luke Schnepp ,  Xian Shi ,  James William Leahy ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Grace Mann ,  Larry Wayne Mann ,  Craig Stacy Takeuchi ,  Peter Lamb ,  David J. Matthews ,  Nicole Miller

IPC: C07D279/16 ,  C07D279/12 ,  C07D417/12 ,  C07D265/36 ,  C07D413/12 ,  C07D403/12 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D411/12 ,  C07D419/12 ,  C07D241/18 ,  C07D241/20 ,  A61K31/55 ,  A61K31/497 ,  A61K31/5355 ,  A61K31/541 ,  C07D305/12 ,  C07D307/79 ,  A61K31/44 ,  A61P35/00

CPC classification number: C07D241/26 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D403/10 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D413/04 ,  C07D413/12

Abstract: This invention relates to compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion, and to pharmaceutical compositions containing such compounds. Even more specifically, the invention relates to compounds that inhibit, regulate and/or modulate kinases, particularly Checkpoint Kinases, even more particularly Checkpoint Kinase 1, or Chk1. Methods of therapeutically or prophylactically using the compounds and compositions to treat kinase-dependent diseases and conditions are also an aspect of the invention, and include methods of treating cancer, as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, by administering effective amounts of such compounds.

Abstract translation: 本发明涉及用于调节蛋白激酶酶活性以调节细胞活性如增殖，分化，程序性细胞死亡，迁移和化学侵蚀的化合物，以及含有这些化合物的药物组合物。 更具体地，本发明涉及抑制，调节和/或调节激酶，特别是检查点激酶，甚至更特别是检查点激酶1或Chk1的化合物。 治疗或预防性地使用化合物和组合物治疗激酶依赖性疾病和病症的方法也是本发明的一个方面，并且包括通过以下方法治疗癌症以及与不期望的血管生成和/或细胞增殖相关的其它疾病状态， 施用有效量的这些化合物。

公开(公告)号：US20090215803A1

公开(公告)日：2009-08-27

申请号：US12083749

申请日：2006-10-23

Applicant: Kenneth D. Rice ,  Neel Kumar Anand ,  Arlyn Arcalas ,  Charles M. Blazey ,  Joerg Bussenius ,  Wai Ki Vickey Chan ,  Hongwang Du ,  Sergey Epshteyn ,  Mohamed Abdulkader Ibrahim ,  Patrick Kearney ,  Abigail R. Kennedy ,  Moon Hwan Kim ,  Jean-Claire Limun Manalo ,  Csaba J. Peto ,  Tsze H. Tsang ,  Amy Lew Tsuhako ,  Peiwen Zhou ,  Elena S. Koltun

Inventor： Kenneth D. Rice ,  Neel Kumar Anand ,  Arlyn Arcalas ,  Charles M. Blazey ,  Joerg Bussenius ,  Wai Ki Vickey Chan ,  Hongwang Du ,  Sergey Epshteyn ,  Mohamed Abdulkader Ibrahim ,  Patrick Kearney ,  Abigail R. Kennedy ,  Moon Hwan Kim ,  Jean-Claire Limun Manalo ,  Csaba J. Peto ,  Tsze H. Tsang ,  Amy Lew Tsuhako ,  Peiwen Zhou ,  Elena S. Koltun

IPC: A61K31/513 ,  C07D403/02 ,  C12N9/99 ,  A61P35/00

CPC classification number: C07D487/04

Abstract: A compound having Formula (I) or a pharmaceutically acceptable salt thereof, wherein X, R1 and R2 are defined in the specification; pharmaceutical compositions thereof; and methods of use thereof.

Abstract translation: 具有式（I）的化合物或其药学上可接受的盐，其中X，R 1和R 2在说明书中定义; 其药物组合物; 及其使用方法。

公开(公告)号：US08697737B2

公开(公告)日：2014-04-15

申请号：US12903031

申请日：2010-10-12

Applicant: Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Larisa Dubenko ,  Abigail R. Kennedy ,  Steven Charles Defina ,  Angie I. Kim ,  Jean-Claire L. Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang ,  Anagha Abhijit Joshi

Inventor： Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Larisa Dubenko ,  Abigail R. Kennedy ,  Steven Charles Defina ,  Angie I. Kim ,  Jean-Claire L. Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang ,  Anagha Abhijit Joshi

IPC: A01N43/56 ,  A61K31/415 ,  C07D231/56

CPC classification number: C07D413/06 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

Abstract: The present invention relates to compounds of the Formula I, wherein G, A, X1, X2, X3, Z, E, Y, and X are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly Raf. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.

Abstract translation: 本发明涉及式I化合物，其中G，A，X 1，X 2，X 3，Z，E，Y和X如本文所定义。 该化合物调节蛋白激酶酶活性以调节细胞活性，如增殖，分化，程序性细胞死亡，迁移和化学侵袭。 本发明的化合物抑制，调节和/或调节激酶，特别是Raf。 使用和制备化合物的方法及其药物组合物治疗激酶依赖性疾病和病症也是本发明的一个方面。

公开(公告)号：US20130165440A1

公开(公告)日：2013-06-27

申请号：US13821435

申请日：2011-09-13

Applicant: Neel Kumar Anand ,  S. David Brown ,  Zerom Tesfai ,  Cristiana A. Zaharia

Inventor： Neel Kumar Anand ,  S. David Brown ,  Zerom Tesfai ,  Cristiana A. Zaharia

IPC: C07D237/34 ,  C07D403/10 ,  C07D409/10 ,  C07D215/44 ,  C07D409/04 ,  C07D403/12 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04

CPC classification number: C07D409/04 ,  C07D217/22 ,  C07D237/34 ,  C07D403/10 ,  C07D405/04 ,  C07D417/10 ,  C07D471/04

Abstract: JAK1 inhibitors of structural formula (I), wherein Ar1, Ar2, Q, W, X, Y, and Z are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases.

Abstract translation: 其中Ar1，Ar2，Q，W，X，Y和Z的结构式（I）的JAK1抑制剂在本说明书中定义，其药学上可接受的盐，其组合物，以及用于治疗疾病的化合物和组合物的用途。 本发明还包括在化合物中和用于制备药物中的用途，特别是用于治疗疾病。

公开(公告)号：US08101625B2

公开(公告)日：2012-01-24

申请号：US12083749

申请日：2006-10-23

Applicant: Kenneth D. Rice ,  Neel Kumar Anand ,  Arlyn Arcalas ,  Charles M. Blazey ,  Joerg Bussenius ,  Wai Ki Vicky Chan ,  Hongwang Du ,  Sergey Epshteyn ,  Mohamed Abdulkader Ibrahim ,  Patrick Kearney ,  Abigail R. Kennedy ,  Moon Hwan Kim ,  Jean-Claire Limun Manalo ,  Csaba J. Peto ,  Tsze H. Tsang ,  Amy Lew Tsuhako ,  Peiwen Zhou ,  Elena S. Koltun

Inventor： Kenneth D. Rice ,  Neel Kumar Anand ,  Arlyn Arcalas ,  Charles M. Blazey ,  Joerg Bussenius ,  Wai Ki Vicky Chan ,  Hongwang Du ,  Sergey Epshteyn ,  Mohamed Abdulkader Ibrahim ,  Patrick Kearney ,  Abigail R. Kennedy ,  Moon Hwan Kim ,  Jean-Claire Limun Manalo ,  Csaba J. Peto ,  Tsze H. Tsang ,  Amy Lew Tsuhako ,  Peiwen Zhou ,  Elena S. Koltun

IPC: A61K31/505 ,  C07D239/02

CPC classification number: C07D487/04

Abstract: A compound having Formula (I) or a pharmaceutically acceptable salt thereof, wherein X, R1 and R2 are defined in the specification; pharmaceutical compositions thereof; and methods of use thereof.

Abstract translation: 具有式（I）的化合物或其药学上可接受的盐，其中X，R 1和R 2在说明书中定义; 其药物组合物; 及其使用方法。

公开(公告)号：US07915250B2

公开(公告)日：2011-03-29

申请号：US12774544

申请日：2010-05-05

Applicant: Naing Aay ,  Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Steven Charles DeFina ,  Larisa Dubenko ,  Anagha Abhijit Joshi ,  Abigail R. Kennedy ,  Angie Inyoung Kim ,  Elena S. Koltun ,  Jean-Claire Limun Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang

Inventor： Naing Aay ,  Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Steven Charles DeFina ,  Larisa Dubenko ,  Anagha Abhijit Joshi ,  Abigail R. Kennedy ,  Angie Inyoung Kim ,  Elena S. Koltun ,  Jean-Claire Limun Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang

IPC: A61K31/397 ,  A61K31/50 ,  A61K31/505 ,  A61K31/4523 ,  A61K31/4178

CPC classification number: C07D205/04 ,  C07D205/06 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

Abstract: Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof. Such compounds are MEK inhibitors and are useful in the treatment of proliferative diseases, such as cancer. Also disclosed are pharmaceutical compositions containing such compounds as well as methods of using the compounds and compositions of the invention in the treatment of cancer.

Abstract translation: 公开了式（I）的化合物及其药学上可接受的盐和溶剂化物。 这些化合物是MEK抑制剂，可用于治疗增殖性疾病如癌症。 还公开了含有这些化合物的药物组合物以及使用本发明化合物和组合物治疗癌症的方法。

公开(公告)号：US07872014B2

公开(公告)日：2011-01-18

申请号：US10565657

申请日：2004-07-23

Applicant: Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Larisa Dubenko ,  Abigail R. Kennedy ,  Richard G. Khoury ,  Angie I. Kim ,  Jean-Claire L. Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang

Inventor： Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Larisa Dubenko ,  Abigail R. Kennedy ,  Richard G. Khoury ,  Angie I. Kim ,  Jean-Claire L. Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang

IPC: C07D471/02 ,  A61K31/4745

CPC classification number: C07D471/04 ,  C07D491/147 ,  C07D519/00

Abstract: The present invention comprises compounds and pharmaceutical compositions comprising the compounds that are inhibitors of ALK. The invention also comprises methods of using the compounds and compositions to treat diseases mediated by ALK, including diseases such as cancer, immunological disorders, cardiovascular diseases, and other degenerative disorders.

Abstract translation: 本发明包括包含作为ALK抑制剂的化合物的化合物和药物组合物。 本发明还包括使用化合物和组合物来治疗由ALK介导的疾病，包括诸如癌症，免疫学障碍，心血管疾病和其它退行性疾病的疾病的方法。

公开(公告)号：US07846959B2

公开(公告)日：2010-12-07

申请号：US11568789

申请日：2005-03-25

Applicant: Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Larisa Dubenko ,  Abigail R. Kennedy ,  Steven Charles Defina ,  Angie I. Kim ,  Jean-Claire L. Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang ,  Anagha Abhijit Joshi

Inventor： Neel Kumar Anand ,  Charles M. Blazey ,  Owen Joseph Bowles ,  Joerg Bussenius ,  Simona Costanzo ,  Jeffry Kimo Curtis ,  Larisa Dubenko ,  Abigail R. Kennedy ,  Steven Charles Defina ,  Angie I. Kim ,  Jean-Claire L. Manalo ,  Csaba J. Peto ,  Kenneth D. Rice ,  Tsze H. Tsang ,  Anagha Abhijit Joshi

IPC: C07D231/02

CPC classification number: C07D413/06 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

Abstract: The present invention relates to compounds of the Formula I, wherein G, A, X1, X2, X3, Z, E, Y, and X are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly Raf. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.

Abstract translation: 本发明涉及式I化合物，其中G，A，X 1，X 2，X 3，Z，E，Y和X如本文所定义。 该化合物调节蛋白激酶酶活性以调节细胞活性，如增殖，分化，程序性细胞死亡，迁移和化学侵袭。 本发明的化合物抑制，调节和/或调节激酶，特别是Raf。 使用和制备化合物的方法及其药物组合物治疗激酶依赖性疾病和病症也是本发明的一个方面。