公开(公告)号：US08367667B2

公开(公告)日：2013-02-05

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： A61K31/40 ,  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：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

公开(公告)号：US08067436B2

公开(公告)日：2011-11-29

申请号：US11753514

申请日：2007-05-24

申请人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Vasu Jammalamadaka ,  Richard George Khoury ,  James William Leahy ,  Morrisson B. Mac ,  Grace Mann ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Craig Stacy Takeuchi ,  Yong Wang ,  Wie Xu

发明人： Lynne Canne Bannen ,  Diva Sze-Ming Chan ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Vasu Jammalamadaka ,  Richard George Khoury ,  James William Leahy ,  Morrisson B. Mac ,  Grace Mann ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Craig Stacy Takeuchi ,  Yong Wang ,  Wie Xu

IPC分类号： A61K31/47 ,  A61K31/4709 ,  A61K31/517 ,  A61K31/5377

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：US07858385B2

公开(公告)日：2010-12-28

申请号：US09859701

申请日：2001-05-16

申请人： Benjamin P. Warner ,  George J. Havrilla ,  Grace Mann

发明人： Benjamin P. Warner ,  George J. Havrilla ,  Grace Mann

IPC分类号： G01N21/76 ,  G01N33/543 ,  G01N33/00

CPC分类号： G01N33/582 ,  G01N33/54373 ,  Y10S430/167 ,  Y10T436/16 ,  Y10T436/18 ,  Y10T436/19

摘要： Method for detecting binding events using micro-X-ray fluorescence spectrometry. Receptors are exposed to at least one potential binder and arrayed on a substrate support. Each member of the array is exposed to X-ray radiation. The magnitude of a detectable X-ray fluorescence signal for at least one element can be used to determine whether a binding event between a binder and a receptor has occurred, and can provide information related to the extent of binding between the binder and receptor.

摘要翻译： 使用微X射线荧光光谱法检测结合事件的方法。 受体暴露于至少一种潜在的粘合剂并排列在基底支架上。 阵列的每个成员暴露于X射线辐射。 可以使用至少一种元素的可检测X射线荧光信号的大小来确定粘合剂和受体之间的结合事件是否已经发生，并且可以提供与粘合剂和受体之间的结合程度相关的信息。

公开(公告)号：US20090170896A1

公开(公告)日：2009-07-02

申请号：US12393806

申请日：2009-02-26

申请人： Lynn Canne Bannen ,  Diva Sze-Ming Chan ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Vasu Jammalamadaka ,  Richard George Khoury ,  James William Leahy ,  Morrison B. Mac ,  Grace Mann ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Craig Stacy Takeuchi ,  Yong Wang ,  Wie Xu

发明人： Lynn Canne Bannen ,  Diva Sze-Ming Chan ,  Jeff Chen ,  Lisa Esther Dalrymple ,  Timothy Patrick Forsyth ,  Tai Phat Huynh ,  Vasu Jammalamadaka ,  Richard George Khoury ,  James William Leahy ,  Morrison B. Mac ,  Grace Mann ,  Larry W. Mann ,  John M. Nuss ,  Jason Jevious Parks ,  Craig Stacy Takeuchi ,  Yong Wang ,  Wie Xu

IPC分类号： A61K31/47 ,  C07D215/20 ,  A61P35/00

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.

公开(公告)号：US20060211709A1

公开(公告)日：2006-09-21

申请号：US10513081

申请日：2003-05-02

申请人： Chris Buhr ,  Tae-Gon Baik ,  Sunghoon Ma ,  Zerom Tesfai ,  Longcheng Wang ,  Erick Co ,  Sergey Epshteyn ,  Abigail Kennedy ,  Baili Chen ,  Larisa Dubenko ,  Neel Anand ,  Tsze Tsang ,  John Nuss ,  Csabaj Peto ,  Kenneth Rice ,  Mohamed Ibrahim ,  Xian Shi ,  James Leahy ,  Jeff Chen ,  Lisa Dalrymple ,  Timothy Forsyth ,  Tai Huynh ,  Grace Mann ,  Larry Mann ,  Craig Takeuchi

发明人： Chris Buhr ,  Tae-Gon Baik ,  Sunghoon Ma ,  Zerom Tesfai ,  Longcheng Wang ,  Erick Co ,  Sergey Epshteyn ,  Abigail Kennedy ,  Baili Chen ,  Larisa Dubenko ,  Neel Anand ,  Tsze Tsang ,  John Nuss ,  Csabaj Peto ,  Kenneth Rice ,  Mohamed Ibrahim ,  Xian Shi ,  James Leahy ,  Jeff Chen ,  Lisa Dalrymple ,  Timothy Forsyth ,  Tai Huynh ,  Grace Mann ,  Larry Mann ,  Craig Takeuchi

IPC分类号： A61K31/497 ,  C07D403/02

CPC分类号： C07D241/26 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D403/10 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D413/04 ,  C07D413/12

摘要： Substituted aryl 1,4-pyrazine derivatives and their use in treating anxiety disorders, depression and stress related disorders are disclosed.

摘要翻译： 公开了取代的芳基1,4-吡嗪衍生物及其在治疗焦虑症，抑郁症和应激相关疾病中的用途。

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：US08088767B2

公开(公告)日：2012-01-03

申请号：US12443103

申请日：2007-09-28

申请人： Adam Antoni Galan ,  Jeff Chen ,  Hongwang Du ,  Timothy Forsyth ,  Tai Phat Huynh ,  Henry William Beecroft Johnson ,  Patrick Kearney ,  James W. Leahy ,  Matthew Sangyup Lee ,  Grace Mann ,  Brian Hugh Ridgway ,  Craig Stacy Takeuchi ,  Peiwen Zhou

发明人： Adam Antoni Galan ,  Jeff Chen ,  Hongwang Du ,  Timothy Forsyth ,  Tai Phat Huynh ,  Henry William Beecroft Johnson ,  Patrick Kearney ,  James W. Leahy ,  Matthew Sangyup Lee ,  Grace Mann ,  Brian Hugh Ridgway ,  Craig Stacy Takeuchi ,  Peiwen Zhou

IPC分类号： A61K31/5377 ,  A61K31/4439 ,  A61K31/4184 ,  C07D413/14 ,  C07D401/14 ,  C07D403/12

CPC分类号： C07D405/14 ,  C07D233/90 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14

摘要： This invention relates to the field of protein tyrosine kinases and inhibitors thereof. In particular, the invention relates to inhibitors of JAK-2, pharmaceutical compositions of the compounds for inhibiting JAK-2, methods of inhibiting JAK-2 in a cell, comprising contacting a cell in which inhibition of JAK-2 is desired with a compound or pharmaceutical composition comprising a compound according to the invention. The also comprises methods of treating a disease or condition that involves JAK-2 comprising administering to a patient a pharmaceutical composition comprising a compound according to the invention.

摘要翻译： 本发明涉及蛋白酪氨酸激酶及其抑制剂的领域。 特别地，本发明涉及JAK-2抑制剂，用于抑制JAK-2的化合物的药物组合物，抑制细胞中JAK-2的方法，包括使需要JAK-2抑制的细胞与化合物 或包含根据本发明的化合物的药物组合物。 还包括治疗涉及JAK-2的疾病或病症的方法，包括向患者施用包含本发明化合物的药物组合物。

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：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