公开(公告)号：US07763627B2

公开(公告)日：2010-07-27

申请号：US10552426

申请日：2004-04-08

Applicant: Mohamed Abdulkader Ibrahim ,  James William Leahy ,  Joan C. Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  John M. Nuss

Inventor： Mohamed Abdulkader Ibrahim ,  James William Leahy ,  Joan C. Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  John M. Nuss

IPC: A61K31/517

CPC classification number: C07D239/94 ,  C07D401/04 ,  C07D405/04

Abstract: A compound according to Formula IV: or a pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof, wherein R1, R2, R3, R4, R5 and X are as defined in the specification.

Abstract translation: 根据式IV的化合物或其药学上可接受的盐，其药物组合物及其使用方法，其中R1，R2，R3，R4，R5和X如说明书中所定义。

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：US20080249079A1

公开(公告)日：2008-10-09

申请号：US11722719

申请日：2005-12-28

Applicant: Jeff Chen ,  Lisa Esther Dalrymple Meyr ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  James W. Leahy ,  Gary Lee Lewis ,  Grace Mann ,  Larry W. Mann ,  Robin Tammie Noguchi ,  Brian Hugh Ridgway ,  Joan Cruz Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  Craig Stacy Takeuchi ,  Matthew Alan Williams ,  John Nuss ,  Atwood K. Cheung

Inventor： Jeff Chen ,  Lisa Esther Dalrymple Meyr ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  James W. Leahy ,  Gary Lee Lewis ,  Grace Mann ,  Larry W. Mann ,  Robin Tammie Noguchi ,  Brian Hugh Ridgway ,  Joan Cruz Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  Craig Stacy Takeuchi ,  Matthew Alan Williams ,  John Nuss ,  Atwood K. Cheung

IPC: A61K31/506 ,  C07D413/14 ,  A61K31/5377 ,  A61K31/519 ,  A61P35/00 ,  C07D403/14 ,  C07D403/12

CPC classification number: C07D413/14 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/14 ,  C07D487/04

Abstract: The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wildtype Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NR1R1a, or O—R1, wherein X is H, halo, C1-C6 alkyl, NO2, mono-, di-, or tri-halo substituted methyl, NR13R,14. C(O)O—C1-C6 alkyl, or N(R13)—C(O)—C1-C6 alkyl; Y is H, halo, OH, C1-C6 alkyl, C0-C6alkyl-NR,15R16, NR15R,6, C1-C6 alkoxy, —N(R13)—(CH2)n-NR15R16, —C(O)O—C1-C6 alkyl, —O—(CH2)n—NR15R16, —C(O)—C1-C6 alkyl, —C0-C6-alkyl-R21, —O—R21, —C(O)—R21, —O—(CH2)n—R21, —C(O)—NR13R14, —C(O)—N(R13)-aryl, —C(O)—N(R13)(CH2)n—NR15R16, —C(O)—N(R13)—(CH2)n-aryl —C(O)—N(R13)—(CH2)n-heterocyclyl; or X and Y together with the atoms to which they are attached form a 4-7 membered heterocyclyl or heteroaryl group containing one or two heteroatoms independently selected from O, N, and S. Z is H, NR2R3, —S—R2a, or —O—R2a

公开(公告)号：US08013156B2

公开(公告)日：2011-09-06

申请号：US10549300

申请日：2004-03-19

Applicant: Lynne Canne Bannen ,  S. David Brown ,  Wei Cheng ,  Vasu Jammalamadaka ,  John M. Nuss ,  Morrison B. Mac ,  Jason Jevious Parks ,  Matthew A. Williams ,  Wei Xu ,  Atwood Kim Cheung ,  Lisa Esther Dalrymple ,  Sergey Epshteyn ,  Mohamed Abdulkader Ibrahim ,  James William Leahy ,  Gary Lee Lewis ,  Robin Tammie Noguchi ,  Larry Wayne Mann ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  Richard George Khoury

Inventor： Lynne Canne Bannen ,  S. David Brown ,  Wei Cheng ,  Vasu Jammalamadaka ,  John M. Nuss ,  Morrison B. Mac ,  Jason Jevious Parks ,  Matthew A. Williams ,  Wei Xu ,  Atwood Kim Cheung ,  Lisa Esther Dalrymple ,  Sergey Epshteyn ,  Mohamed Abdulkader Ibrahim ,  James William Leahy ,  Gary Lee Lewis ,  Robin Tammie Noguchi ,  Larry Wayne Mann ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  Richard George Khoury

IPC: C07D401/14 ,  C07D403/14 ,  A61K31/4425 ,  A61K31/495 ,  A61K31/506 ,  A61P19/02 ,  A61P35/00

CPC classification number: A61K31/496 ,  C07D213/75 ,  C07D239/42 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D417/12 ,  C07D417/14

Abstract: The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly Tie-2. Methods of using the compounds and pharmaceutical compositions thereof to treat kinase-dependent diseases and conditions are also an aspect of the invention.

Abstract translation: 本发明提供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。 本发明的化合物抑制，调节和/或调节激酶，特别是Tie-2。 使用化合物及其药物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。

公开(公告)号：US08211929B2

公开(公告)日：2012-07-03

申请号：US11722719

申请日：2005-12-28

Applicant: Jeff Chen ,  Lisa Esther Dalrymple Meyr ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  James W. Leahy ,  Gary Lee Lewis ,  Grace Mann ,  Larry W. Mann ,  Robin Tammie Noguchi ,  Brian Hugh Ridgway ,  Joan Cruz Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  Craig Stacy Takeuchi ,  Matthew Alan Williams ,  John Nuss ,  Atwood K. Cheung

Inventor： Jeff Chen ,  Lisa Esther Dalrymple Meyr ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  James W. Leahy ,  Gary Lee Lewis ,  Grace Mann ,  Larry W. Mann ,  Robin Tammie Noguchi ,  Brian Hugh Ridgway ,  Joan Cruz Sangalang ,  Kevin Luke Schnepp ,  Xian Shi ,  Craig Stacy Takeuchi ,  Matthew Alan Williams ,  John Nuss ,  Atwood K. Cheung

IPC: A01N43/56 ,  A61K31/415 ,  C07D239/02 ,  C07D231/00

CPC classification number: C07D413/14 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/14 ,  C07D487/04

Abstract: The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wildtype Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NR1R1a, or O—R1, wherein X is H, halo, C1-C6 alkyl, NO2, mono-, di-, or tri-halo substituted methyl, NR13R,14. C(O)O—C1-C6 alkyl, or N(R13)—C(O)—C1-C6 alkyl; Y is H, halo, OH, C1-C6 alkyl, C0-C6alkyl-NR,15R16, NR15R,6, C1-C6 alkoxy, —N(R13)—(CH2)n-NR15R16, —C(O)O—C1-C6 alkyl, —O—(CH2)n—NR15R16, —C(O)—C1-C6 alkyl, —C0-C6-alkyl-R21, —O—R21, —C(O)—R21, —O—(CH2)n—R21, —C(O)—NR13R14, —C(O)—N(R13)-aryl, —C(O)—N(R13)(CH2)n—NR15R16, —C(O)—N(R13)—(CH2)n-aryl —C(O)—N(R13)—(CH2)n-heterocyclyl; or X and Y together with the atoms to which they are attached form a 4-7 membered heterocyclyl or heteroaryl group containing one or two heteroatoms independently selected from O, N, and S. Z is H, NR2R3, —S—R2a, or —O—R2a