公开(公告)号：US08440663B2

公开(公告)日：2013-05-14

申请号：US11992224

申请日：2007-01-30

申请人： Grace Mann ,  Naing Aay ,  Arlyn Arcalas ,  S. David Brown ,  Wai Ki Vicky Chan ,  Jeff Chen ,  Hongwang Du ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Adam A. Galan ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  Henry William Beecroft Johnson ,  Brian Kane ,  Patrick Kearney ,  Byung Gyu Kim ,  Elena S. Koltun ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Lisa E. Meyr ,  Robin Tammie Noguchi ,  Michael Pack ,  Brian Hugh Ridgway ,  Xian Shi ,  John Woolfrey ,  Peiwen Zhou

发明人： Grace Mann ,  Naing Aay ,  Arlyn Arcalas ,  S. David Brown ,  Wai Ki Vicky Chan ,  Jeff Chen ,  Hongwang Du ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Adam A. Galan ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  Henry William Beecroft Johnson ,  Brian Kane ,  Patrick Kearney ,  Byung Gyu Kim ,  Elena S. Koltun ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Lisa E. Meyr ,  Robin Tammie Noguchi ,  Michael Pack ,  Brian Hugh Ridgway ,  Xian Shi ,  John Woolfrey ,  Peiwen Zhou

IPC分类号： A61K31/535 ,  C07D239/24 ,  C07D401/10 ,  C07D413/10

CPC分类号： C07D239/42 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12 ,  C07D453/02 ,  C07D487/04

摘要： This invention relates to certain pyrimidine derivative inhibitors of JAK-2, having Formula (I): wherein D, E, L, Z, R1, R2, R25, and n1 are as defined in the specification, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof.

摘要翻译： 本发明涉及具有式（I）的JAK-2的某些嘧啶衍生物抑制剂：其中D，E，L，Z，R 1，R 2，R 25和n 1如说明书中所定义，其药学上可接受的盐，药物组合物 及其使用方法。

公开(公告)号：US20090298830A1

公开(公告)日：2009-12-03

申请号：US11992224

申请日：2007-01-30

申请人： Grace Mann ,  Naing Aay ,  Arlyn Arcalas ,  S. David Brown ,  Wai Ki Vicky Chan ,  Jeff Chen ,  Hongwang Du ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Adam A. Galan ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  Henry William Beecroft Johnson ,  Brian Kane ,  Patrick Kearney ,  Byung Gyu Kim ,  Elena S. Koltun ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Lisa E. Meyr ,  Robin Tammie Noguchi ,  Michael Pack ,  Brian Hugh Ridgway ,  Xian Shi ,  John Woolfrey ,  Peiwen Zhou

发明人： Grace Mann ,  Naing Aay ,  Arlyn Arcalas ,  S. David Brown ,  Wai Ki Vicky Chan ,  Jeff Chen ,  Hongwang Du ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Adam A. Galan ,  Tai Phat Huynh ,  Mohamed Abdulkader Ibrahim ,  Henry William Beecroft Johnson ,  Brian Kane ,  Patrick Kearney ,  Byung Gyu Kim ,  Elena S. Koltun ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Lisa E. Meyr ,  Robin Tammie Noguchi ,  Michael Pack ,  Brian Hugh Ridgway ,  Xian Shi ,  John Woolfrey ,  Peiwen Zhou

IPC分类号： A61K31/5377 ,  C07D413/14 ,  A61P7/00

CPC分类号： C07D239/42 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12 ,  C07D453/02 ,  C07D487/04

摘要： This invention relates to certain pyrimidine derivative inhibitors of JAK-2, having Formula (I): wherein D, E, L, Z, R1, R2, R25, and n1 are as defined in the specification, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof.

摘要翻译： 本发明涉及具有式（I）的JAK-2的某些嘧啶衍生物抑制剂：其中D，E，L，Z，R 1，R 2，R 25和n 1如说明书中所定义，其药学上可接受的盐，药物组合物 及其使用方法。

公开(公告)号：US20120238570A1

公开(公告)日：2012-09-20

申请号：US13487559

申请日：2012-06-04

申请人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

发明人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

IPC分类号： A61K31/517 ,  A61K31/519 ,  C07D413/04 ,  A61P35/00 ,  C07D239/84 ,  C07D471/04 ,  C07D403/12 ,  A61K31/5377 ,  C07D239/70

CPC分类号： C07D239/42 ,  C07D239/70 ,  C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D403/12

摘要： The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.

摘要翻译： 本发明涉及式I化合物或其单一异构体; 其中除了制备式I化合物的方法之外，化合物任选为其药学上可接受的盐，水合物，溶剂合物或其组合，以及使用式I化合物治疗癌症的方法。

公开(公告)号：US08222263B2

公开(公告)日：2012-07-17

申请号：US12049225

申请日：2008-03-14

申请人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

发明人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

IPC分类号： A61K31/517 ,  A01N43/54

CPC分类号： C07D239/42 ,  C07D239/70 ,  C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D403/12

摘要： The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.

摘要翻译： 本发明涉及式I化合物或其单一异构体; 其中除了制备式I化合物的方法之外，化合物任选为其药学上可接受的盐，水合物，溶剂合物或其组合，以及使用式I化合物治疗癌症的方法。

公开(公告)号：US08754092B2

公开(公告)日：2014-06-17

申请号：US13487594

申请日：2012-06-04

申请人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

发明人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

IPC分类号： A01N43/54 ,  A61K31/517 ,  C07D239/72 ,  C07D401/00

CPC分类号： C07D239/42 ,  C07D239/70 ,  C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D403/12

摘要： The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.

公开(公告)号：US20090105211A1

公开(公告)日：2009-04-23

申请号：US12049225

申请日：2008-03-14

申请人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

发明人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

IPC分类号： C07D239/84 ,  C07D413/12 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/553 ,  A61K31/55 ,  C07D401/12 ,  C07D403/12 ,  A61P35/00 ,  C07D401/14

CPC分类号： C07D239/42 ,  C07D239/70 ,  C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D403/12

摘要： The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.

摘要翻译： 本发明涉及式I化合物或其单一异构体; 其中除了制备式I化合物的方法之外，化合物任选为其药学上可接受的盐，水合物，溶剂合物或其组合，以及使用式I化合物治疗癌症的方法。

公开(公告)号：US08796294B2

公开(公告)日：2014-08-05

申请号：US13487559

申请日：2012-06-04

申请人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

发明人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

IPC分类号： A01N43/54 ,  A61K31/517 ,  C07D239/72 ,  C07D401/00

CPC分类号： C07D239/42 ,  C07D239/70 ,  C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D403/12

摘要： The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.

摘要翻译： 本发明涉及式I化合物或其单一异构体; 其中除了制备式I化合物的方法之外，化合物任选为其药学上可接受的盐，水合物，溶剂合物或其组合，以及使用式I化合物治疗癌症的方法。

公开(公告)号：US20120245139A1

公开(公告)日：2012-09-27

申请号：US13487594

申请日：2012-06-04

申请人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

发明人： Suleyman Bahceci ,  William Bajjalieh ,  Jeff Chen ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Byung Gyu Kim ,  James W. Leahy ,  Matthew Sangyup Lee ,  Gary L. Lewis ,  Morrison B. Mac ,  Grace Mann ,  Charles K. Marlowe ,  Brian Hugh Ridgway ,  Joan C. Sangalang ,  Xian Shi ,  Craig Stacy Takeuchi ,  Yong Wang

IPC分类号： A61K31/517 ,  A61P35/00 ,  A61K31/55 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/553

CPC分类号： C07D239/42 ,  C07D239/70 ,  C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D403/12

摘要： The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.

公开(公告)号：US20080249079A1

公开(公告)日：2008-10-09

申请号：US11722719

申请日：2005-12-28

申请人： 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

发明人： 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分类号： A61K31/506 ,  C07D413/14 ,  A61K31/5377 ,  A61K31/519 ,  A61P35/00 ,  C07D403/14 ,  C07D403/12

CPC分类号： C07D413/14 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/14 ,  C07D487/04

摘要： 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：US08211929B2

公开(公告)日：2012-07-03

申请号：US11722719

申请日：2005-12-28

申请人： 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

发明人： 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分类号： A01N43/56 ,  A61K31/415 ,  C07D239/02 ,  C07D231/00

CPC分类号： C07D413/14 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/14 ,  C07D487/04

摘要： 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