公开(公告)号：US07579473B2

公开(公告)日：2009-08-25

申请号：US12393806

申请日：2009-02-26

申请人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Timothy Patrick Forsyth ,  Richard George Khoury ,  James William Leahy ,  Morrisson B. Mac ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Yong Wang ,  Wie Xu

发明人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Timothy Patrick Forsyth ,  Richard George Khoury ,  James William Leahy ,  Morrisson B. Mac ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Yong Wang ,  Wie Xu

IPC分类号： C07D215/38 ,  A61K31/47

CPC分类号： C07D215/233 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/501 ,  A61K31/505 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  C07D215/22 ,  C07D215/36 ,  C07D215/38 ,  C07D215/46 ,  C07D239/88 ,  C07D239/94 ,  C07D295/15 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C12Q1/485 ,  G01N2500/04 ,  Y02A50/393

摘要： 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. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

摘要翻译： 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。 更具体地，本发明提供抑制，调节和/或调节与细胞活性变化相关的激酶受体，特别是c-Met，KDF，c-Kit，flt-3和flt-4信号转导途径的喹唑啉和喹啉 如上所述，含有这些化合物的组合物，及其用于治疗激酶依赖性疾病和病症的方法。 本发明还提供了制备上述化合物的方法和含有这些化合物的组合物。

公开(公告)号：US08178532B2

公开(公告)日：2012-05-15

申请号：US11753462

申请日：2007-05-24

申请人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Timothy Patrick Forsyth ,  Richard George Khoury ,  James William Leahy ,  Morrisson B. Mac ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Yong Wang ,  Wie Xu

发明人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Timothy Patrick Forsyth ,  Richard George Khoury ,  James William Leahy ,  Morrisson B. Mac ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Yong Wang ,  Wie Xu

IPC分类号： A61K31/535 ,  C07D413/00

CPC分类号： C07D215/233 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/501 ,  A61K31/505 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  C07D215/22 ,  C07D215/36 ,  C07D215/38 ,  C07D215/46 ,  C07D239/88 ,  C07D239/94 ,  C07D295/15 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C12Q1/485 ,  G01N2500/04 ,  Y02A50/393

摘要： 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. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

摘要翻译： 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。 更具体地，本发明提供抑制，调节和/或调节与细胞活性变化相关的激酶受体，特别是c-Met，KDF，c-Kit，flt-3和flt-4信号转导途径的喹唑啉和喹啉 如上所述，含有这些化合物的组合物，及其用于治疗激酶依赖性疾病和病症的方法。 本发明还提供了制备上述化合物的方法和含有这些化合物的组合物。

公开(公告)号：US20120070368A1

公开(公告)日：2012-03-22

申请号：US13087094

申请日：2011-04-14

申请人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Timothy Patrick Forsyth ,  Richard George Khoury ,  James William Leahy ,  Morrison B. Mac ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Yong Wang ,  Wei Xu ,  Diane Simeone

发明人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Timothy Patrick Forsyth ,  Richard George Khoury ,  James William Leahy ,  Morrison B. Mac ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Yong Wang ,  Wei Xu ,  Diane Simeone

IPC分类号： A61K31/47 ,  A61P35/02 ,  A61K51/00 ,  A61P35/00 ,  A61K38/22 ,  A61K39/395

CPC分类号： A61K31/47 ,  A61K31/517 ,  A61K31/7068 ,  A61K45/06 ,  A61N5/10 ,  A61K2300/00

摘要： Disclosed are methods of treating cancer by administering a compound of Formula I, or a pharmaceutically acceptable salt thereof, in combination with gemcitabine (GEM), or a pharmaceutically acceptable salt thereof, and optionally one or more additional treatments, wherein:R1 is halo;R2 is halo;R3 is (C1-C6)alkyl;R4 is (C1-C6)alkyl; andQ is CH or N.

摘要翻译： 公开了通过给予式I化合物或其药学上可接受的盐与吉西他滨（GEM）或其药学上可接受的盐以及任选的一种或多种另外的治疗组合治疗癌症的方法，其中：R1是卤素; R2是卤素; R3是（C1-C6）烷基; R4是（C1-C6）烷基; Q为CH或N.

公开(公告)号：US20080234270A1

公开(公告)日：2008-09-25

申请号：US11572962

申请日：2005-07-30

申请人： Lynne Canne Bannen ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Brenton T. Flatt ,  Timothy Patrick Forsyth ,  Xiao-Hui Gu ,  Morrison B. Mac ,  Larry W. Mann ,  Grace Mann ,  Richard Martin ,  Raju Mohan ,  Brett Murphy ,  Michael Charles Nyman ,  William C. Stevens ,  Tie-Lin Wang ,  Yong Wang ,  Jason H. Wu

发明人： Lynne Canne Bannen ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Brenton T. Flatt ,  Timothy Patrick Forsyth ,  Xiao-Hui Gu ,  Morrison B. Mac ,  Larry W. Mann ,  Grace Mann ,  Richard Martin ,  Raju Mohan ,  Brett Murphy ,  Michael Charles Nyman ,  William C. Stevens ,  Tie-Lin Wang ,  Yong Wang ,  Jason H. Wu

IPC分类号： A61K31/40 ,  C07D207/34 ,  C07D403/02 ,  C07D413/02 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/506

CPC分类号： C07D207/416 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

摘要： Compounds, compositions and methods for modulating the activity of receptors are provided. In particular compounds and compositions are provided for modulating the activity of receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder directly or indirectly related to the activity of the receptors.

摘要翻译： 提供了调节受体活性的化合物，组合物和方法。 特别地提供化合物和组合物用于调节受体的活性和用于治疗，预防或改善与受体活性直接或间接相关的疾病或病症的一种或多种症状。

公开(公告)号：US20110301128A1

公开(公告)日：2011-12-08

申请号：US13214665

申请日：2011-08-22

申请人： Lynne Canne Bannen ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Brenton T. Flatt ,  Timothy Patrick Forsyth ,  Xiao-Hui Gu ,  Morrison B. Mac ,  Larry W. Mann ,  Grace Mann ,  Richard Martin ,  Raju Mohan ,  Brett Murphy ,  Michael Charles Nyman ,  William C. Stevens ,  Tie-Lin Wang ,  Yong Wang ,  Jason H. Wu

发明人： Lynne Canne Bannen ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Brenton T. Flatt ,  Timothy Patrick Forsyth ,  Xiao-Hui Gu ,  Morrison B. Mac ,  Larry W. Mann ,  Grace Mann ,  Richard Martin ,  Raju Mohan ,  Brett Murphy ,  Michael Charles Nyman ,  William C. Stevens ,  Tie-Lin Wang ,  Yong Wang ,  Jason H. Wu

IPC分类号： A61K31/635 ,  A61K31/4155 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/433 ,  A61K31/4025 ,  A61K31/4725 ,  A61K31/4709 ,  A61K31/506 ,  A61K31/428 ,  A61K31/40 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/55 ,  A61P9/00 ,  A61P21/00 ,  A61P17/00 ,  A61P13/12 ,  A61P25/00 ,  A61P19/00 ,  A61P37/02 ,  A61P3/00 ,  A61P35/00 ,  A61P15/08 ,  A61P5/00 ,  A61K31/402

CPC分类号： C07D207/416 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

摘要： Compounds, compositions and methods for modulating the activity of receptors are provided. In particular compounds and compositions are provided for modulating the activity of receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder directly or indirectly related to the activity of the receptors.

摘要翻译： 提供了调节受体活性的化合物，组合物和方法。 特别地提供化合物和组合物用于调节受体的活性和用于治疗，预防或改善与受体活性直接或间接相关的疾病或病症的一种或多种症状。

公开(公告)号：US08178570B2

公开(公告)日：2012-05-15

申请号：US10552424

申请日：2004-04-08

申请人： Jeff Chen ,  Lisa Esther Dalrymple ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  James William Leahy ,  Brian Hugh Ridgway ,  Grace Mann ,  Larry W. Mann ,  Craig Stacy Takeuchi ,  Joan C. Sangalang

发明人： Jeff Chen ,  Lisa Esther Dalrymple ,  Sergey Epshteyn ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  James William Leahy ,  Brian Hugh Ridgway ,  Grace Mann ,  Larry W. Mann ,  Craig Stacy Takeuchi ,  Joan C. Sangalang

IPC分类号： A01N43/64 ,  A01N43/54 ,  A61K31/41 ,  C07D239/42 ,  C07D401/04 ,  C07D249/08

CPC分类号： C07D401/04 ,  A61K31/4439 ,  A61K31/506

摘要： 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.

摘要翻译： 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：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