公开(公告)号：US20110263673A1

公开(公告)日：2011-10-27

申请号：US13122147

申请日：2009-10-07

申请人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Kazumasa Aoki ,  Hiroyuki Tsuruoka ,  Noriyuki Hayashi ,  Tsuyoshi Homma

发明人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Kazumasa Aoki ,  Hiroyuki Tsuruoka ,  Noriyuki Hayashi ,  Tsuyoshi Homma

IPC分类号： A61K31/40 ,  C12N5/071 ,  A61P3/10 ,  A61P9/10 ,  C07D207/34 ,  A61P9/00

CPC分类号： C07D207/34

摘要： The present invention comprises a compound for the prevention and/or treatment of cardiovascular diseases. The compound is an atropisomer of a compound represented by the following general formula (I): wherein R1 represents a C1-C3 alkyl group; R2 represents a 2-hydroxy-C4-C6 alkyl group; R3 represents a halogeno group, a halogeno-C1-C3 alkyl group and the like; R4 represents a hydrogen atom, a halogeno group and the like; R5 represents a C1-C3 alkyl group; and R6 represents a hydrogen atom, a halogeno group and the like] or atropisomers thereof.

摘要翻译： 本发明包括用于预防和/或治疗心血管疾病的化合物。 该化合物是由以下通式（I）表示的化合物的阻转异构体：其中R1表示C1-C3烷基; R2表示2-羟基-C4-C6烷基; R 3表示卤代基，卤代-C 1 -C 3烷基等; R4代表氢原子，卤代基等; R5代表C1-C3烷基; R6表示氢原子，卤代基等]或它们的阻转异构体。

公开(公告)号：US08487117B2

公开(公告)日：2013-07-16

申请号：US13122147

申请日：2009-10-07

申请人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Kazumasa Aoki ,  Hiroyuki Tsuruoka ,  Noriyuki Hayashi ,  Tsuyoshi Homma

发明人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Kazumasa Aoki ,  Hiroyuki Tsuruoka ,  Noriyuki Hayashi ,  Tsuyoshi Homma

IPC分类号： C07D207/30 ,  A61K31/40

CPC分类号： C07D207/34

摘要： The present invention comprises a compound for the prevention and/or treatment of cardiovascular diseases. The compound is an atropisomer of a compound represented by the following general formula (I): wherein R1 represents a C1-C3 alkyl group; R2 represents a 2-hydroxy-C4-C6 alkyl group; R3 represents a halogeno group, a halogeno-C1-C3 alkyl group and the like; R4 represents a hydrogen atom, a halogeno group and the like; R5 represents a C1-C3 alkyl group; and R6 represents a hydrogen atom, a halogeno group and the like] or atropisomers thereof.

摘要翻译： 本发明包括用于预防和/或治疗心血管疾病的化合物。 该化合物是由以下通式（I）表示的化合物的阻转异构体：其中R1表示C1-C3烷基; R2表示2-羟基-C4-C6烷基; R 3表示卤代基，卤代-C 1 -C 3烷基等; R4代表氢原子，卤代基等; R5代表C1-C3烷基; R6表示氢原子，卤代基等]或它们的阻转异构体。

公开(公告)号：US08642640B2

公开(公告)日：2014-02-04

申请号：US13122239

申请日：2009-10-07

申请人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Hiroyuki Tsuruoka ,  Kazumasa Aoki ,  Masatoshi Honzumi ,  Yusuke Asoh ,  Keiji Saito ,  Tsuyoshi Homma

发明人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Hiroyuki Tsuruoka ,  Kazumasa Aoki ,  Masatoshi Honzumi ,  Yusuke Asoh ,  Keiji Saito ,  Tsuyoshi Homma

IPC分类号： A61K31/40 ,  C07D207/08

CPC分类号： C07D207/34

摘要： The present invention comprises a compound for the prevention and/or treatment of cardiovascular diseases, nephropathy, fibrosis, primary aldosteronism or edema. The compound is of the following general formula (I): wherein R1 represents a C1-C3 alkyl group; R2 represents a hydroxy-C1-C4 alkyl group and the like; R3 represents a halogeno group, a halogeno-C1-C3 alkyl group and the like; R4 represents a hydrogen atom, a halogeno group and the like, —R5 represents a sulfamoyl group or a C1-C3 alkylsulfonyl group; R6 represents a hydrogen atom, a halogeno group and the like] or an N-oxide, atropisomer of the foregoing, or pharmaceutically acceptable salt of the foregoing.

摘要翻译： 本发明包括用于预防和/或治疗心血管疾病，肾病，纤维化，原发性醛固酮增多症或水肿的化合物。 该化合物具有以下通式（I）：其中R 1表示C 1 -C 3烷基; R2表示羟基-C1-C4烷基等; R 3表示卤代基，卤代-C 1 -C 3烷基等; R4表示氢原子，卤代基等，-R5表示氨磺酰基或C1-C3烷基磺酰基; R6表示氢原子，卤代基等]或上述的N-氧化物，阻转异构体或上述的药学上可接受的盐。

公开(公告)号：US20110263544A1

公开(公告)日：2011-10-27

申请号：US13122239

申请日：2009-10-07

申请人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Hiroyuki Tsuruoka ,  Kazumasa Aoki ,  Masatoshi Honzumi ,  Yusuke Asoh ,  Keiji Saito ,  Tsuyoshi Homma

发明人： John Nuss ,  Matthew Williams ,  Raju Mohan ,  Richard Martin ,  Tie-Lin Wang ,  Hiroyuki Tsuruoka ,  Kazumasa Aoki ,  Masatoshi Honzumi ,  Yusuke Asoh ,  Keiji Saito ,  Tsuyoshi Homma

IPC分类号： A61K31/635 ,  A61K31/402 ,  A61P9/10 ,  C12N5/071 ,  A61P13/12 ,  A61P5/42 ,  A61P7/10 ,  C07D207/34 ,  A61P9/12

CPC分类号： C07D207/34

摘要： The present invention comprises a compound for the prevention and/or treatment of cardiovascular diseases, nephropathy, fibrosis, primary aldosteronism or edema. The compound is of the following general formula (I): wherein R1 represents a C1-C3 alkyl group; R2 represents a hydroxy-C1-C4 alkyl group and the like; R3 represents a halogeno group, a halogeno-C1-C3 alkyl group and the like; R4 represents a hydrogen atom, a halogeno group and the like, —R5 represents a sulfamoyl group or a C1-C3 alkylsulfonyl group; R6 represents a hydrogen atom, a halogeno group and the like] or an N-oxide, atropisomer of the foregoing, or pharmaceutically acceptable salt of the foregoing.

摘要翻译： 本发明包括用于预防和/或治疗心血管疾病，肾病，纤维化，原发性醛固酮增多症或水肿的化合物。 该化合物具有以下通式（I）：其中R 1表示C 1 -C 3烷基; R2表示羟基-C1-C4烷基等; R 3表示卤代基，卤代-C 1 -C 3烷基等; R4表示氢原子，卤代基等，-R5表示氨磺酰基或C1-C3烷基磺酰基; R6表示氢原子，卤代基等]或上述的N-氧化物，阻转异构体或上述的药学上可接受的盐。

公开(公告)号：US20070208166A1

公开(公告)日：2007-09-06

申请号：US10576932

申请日：2004-10-22

申请人： Deborah Baly ,  Adam Galan ,  Mohamed Ibrahim ,  Christopher Jaeger ,  Patrick Kearney ,  James Leahy ,  Gary Lewis ,  Kirk McMillan ,  Robin Noguchi ,  John Nuss ,  Jason Parks ,  Kevin Schnepp ,  Xian Shi ,  Matthew Williams ,  Wei Xu ,  Wentao Zhang

发明人： Deborah Baly ,  Adam Galan ,  Mohamed Ibrahim ,  Christopher Jaeger ,  Patrick Kearney ,  James Leahy ,  Gary Lewis ,  Kirk McMillan ,  Robin Noguchi ,  John Nuss ,  Jason Parks ,  Kevin Schnepp ,  Xian Shi ,  Matthew Williams ,  Wei Xu ,  Wentao Zhang

IPC分类号： C07D471/02

CPC分类号： C07C237/22 ,  C07C275/16 ,  C07C275/34 ,  C07C2602/10 ,  C07D207/16 ,  C07D209/20 ,  C07D209/42 ,  C07D209/44 ,  C07D213/56 ,  C07D213/75 ,  C07D215/48 ,  C07D215/54 ,  C07D217/06 ,  C07D217/22 ,  C07D233/56 ,  C07D233/58 ,  C07D263/32 ,  C07D277/46 ,  C07D277/66 ,  C07D277/82 ,  C07D295/155 ,  C07D295/185 ,  C07D319/20 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/12 ,  C07D471/04 ,  C07D495/04 ,  C07D513/04

摘要： The invention provides compounds and methods for inhibition of kinases, such as those of the TAO family, more specifically KIAA1361, TAO, and JIK kinases. 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.

摘要翻译： 本发明提供了用于抑制激酶的化合物和方法，例如TAO族的那些，更具体地是KIAA1361，TAO和JIK激酶。 本发明提供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。 本发明的化合物抑制，调节和/或调节与上述细胞活性变化相关的激酶受体信号转导途径，本发明包括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 。

公开(公告)号：US20070275952A1

公开(公告)日：2007-11-29

申请号：US10549300

申请日：2004-03-19

申请人： Lynne Bannen ,  S. Brown ,  Wei Cheng ,  Vasu Jammalamadaka ,  John Nuss ,  Morrison Mac ,  Jason Parks ,  Matthew Williams ,  Wei Xu ,  Atwood Cheung ,  Lisa Dalrymple ,  Sergey Epshteyn ,  Mohamed Ibrahim ,  James Leahy ,  Gary Lewis ,  Robin Noguchi ,  Larry Mann ,  Brian Ridway ,  Joan Sangalang ,  Kevin Schnepp ,  Xian Shi ,  Richard Khoury

发明人： Lynne Bannen ,  S. Brown ,  Wei Cheng ,  Vasu Jammalamadaka ,  John Nuss ,  Morrison Mac ,  Jason Parks ,  Matthew Williams ,  Wei Xu ,  Atwood Cheung ,  Lisa Dalrymple ,  Sergey Epshteyn ,  Mohamed Ibrahim ,  James Leahy ,  Gary Lewis ,  Robin Noguchi ,  Larry Mann ,  Brian Ridway ,  Joan Sangalang ,  Kevin Schnepp ,  Xian Shi ,  Richard Khoury

IPC分类号： A61K31/41 ,  A61K31/44 ,  A61K31/445 ,  A61K31/497 ,  A61K31/535 ,  A61K31/551 ,  A61P35/00 ,  C07D243/08 ,  C07D285/10 ,  C07D401/14 ,  C07D413/00 ,  C07D417/02 ,  C12N5/00 ,  C12Q1/00

CPC分类号： A61K31/496 ,  C07D213/75 ,  C07D239/42 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D417/12 ,  C07D417/14

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：US07994172B2

公开(公告)日：2011-08-09

申请号：US11722291

申请日：2005-12-27

申请人： Ken Rice ,  Erick Wang Co ,  Moon Hwan Kim ,  Lynn Canne Bannen ,  Joerg Bussenius ,  Donna Tra Le ,  Amy Lew Tsuhako ,  John Nuss ,  Yong Wang ,  Wei Xu ,  Rhett Ronald Klein

发明人： Ken Rice ,  Erick Wang Co ,  Moon Hwan Kim ,  Lynn Canne Bannen ,  Joerg Bussenius ,  Donna Tra Le ,  Amy Lew Tsuhako ,  John Nuss ,  Yong Wang ,  Wei Xu ,  Rhett Ronald Klein

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P35/00

CPC分类号： C07D487/04

摘要： The invention provides compounds of formula (I) and methods for inhibition of kinases, more specifically p70S6 kinases, and more preferably p70S6, Akt-1 and Akt-2 kinases. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration, chemoinvasion and metabolism. 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.

摘要翻译： 本发明提供式（I）化合物和抑制激酶，更特别是p70S6激酶，更优选p70S6，Akt-1和Akt-2激酶的方法。 本发明提供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，化学侵袭和代谢的化合物。 本发明的化合物抑制，调节和/或调节与上述细胞活性变化相关的激酶受体信号转导途径，本发明包括含有这些化合物的组合物，以及使用它们治疗激酶依赖性疾病和病症的方法 。

公开(公告)号：US20070225307A1

公开(公告)日：2007-09-27

申请号：US11753462

申请日：2007-05-24

申请人： Lynne Bannen ,  Diva Chan ,  Jeff Chen ,  Lisa Dalrymple ,  Timothy Forsyth ,  Tai Huynh ,  Vasu Jammalamadaka ,  Richard Khoury ,  James Leahy ,  Morrison Mac ,  Grace Mann ,  Larry Mann ,  John Nuss ,  Jason Parks ,  Craig Takeuchi ,  Yong Wang ,  Wie Xu

发明人： Lynne Bannen ,  Diva Chan ,  Jeff Chen ,  Lisa Dalrymple ,  Timothy Forsyth ,  Tai Huynh ,  Vasu Jammalamadaka ,  Richard Khoury ,  James Leahy ,  Morrison Mac ,  Grace Mann ,  Larry Mann ,  John Nuss ,  Jason Parks ,  Craig Takeuchi ,  Yong Wang ,  Wie Xu

IPC分类号： A61K31/517 ,  A61K31/4709 ,  A61K31/4704 ,  C07D401/02 ,  C07D403/02 ,  C07D417/02

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：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：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。