公开(公告)号：WO2010096314A1

公开(公告)日：2010-08-26

申请号：PCT/US2010/023764

申请日：2010-02-10

Applicant: AMGEN INC. ,  BOEZIO, Alessandro ,  CHENG, Alan, C. ,  COATS, James, R. ,  COPELAND, Katrina, W. ,  GRACEFFA, Russell ,  HARMANGE, Jean-Christophe ,  HUANG, Hongbing ,  LA, Daniel ,  OLIVIERI, Philip, R. ,  PETERSON, Emily, A. ,  SCHENKEL, Laurie

Inventor： BOEZIO, Alessandro ,  CHENG, Alan, C. ,  COATS, James, R. ,  COPELAND, Katrina, W. ,  GRACEFFA, Russell ,  HARMANGE, Jean-Christophe ,  HUANG, Hongbing ,  LA, Daniel ,  OLIVIERI, Philip, R. ,  PETERSON, Emily, A. ,  SCHENKEL, Laurie

IPC: C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  A61K31/53 ,  A61K31/506 ,  A61K31/5355 ,  A61P35/00

CPC classification number: C07D403/14 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Abstract translation: 本发明提供了化合物，其是激酶抑制剂，特别是PIK激酶抑制剂，更具体地，mTOR抑制剂，因此可用于治疗通过抑制激酶可治疗的疾病，特别是PIK激酶抑制剂，更具体地，mTOR如癌症。 还提供含有这些化合物的药物组合物和制备这些化合物的方法。

公开(公告)号：WO2006012374A1

公开(公告)日：2006-02-02

申请号：PCT/US2005/025800

申请日：2005-07-20

Applicant: AMGEN INC. ,  YUAN, Chester Chenguang ,  YANG, Kevin ,  VANDERPLAS, Simon ,  RIAHI, Babak ,  POTASHMAN, Michele ,  PATEL, Vinod F. ,  NOMAK, Rana ,  LI, Aiwen ,  HUANG, Qi ,  HARMANGE, Jean-Christophe ,  ASKEW, JR., Benny C.

Inventor： YUAN, Chester Chenguang ,  YANG, Kevin ,  VANDERPLAS, Simon ,  RIAHI, Babak ,  POTASHMAN, Michele ,  PATEL, Vinod F. ,  NOMAK, Rana ,  LI, Aiwen ,  HUANG, Qi ,  HARMANGE, Jean-Christophe ,  ASKEW, JR., Benny C.

IPC: C07D401/12 ,  C07D413/14 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D217/02 ,  C07D403/12 ,  C07D417/14 ,  C07D471/04 ,  A61K31/443 ,  A61K31/4427 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4725 ,  A61P35/00

CPC classification number: C07D401/12 ,  C07D217/02 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: The present invention provides classes of compounds, including-their pharmaceutically acceptable derivatives, useful for treating angiogenesis and related diseases such as cancer. Formula I and II wherein R is a 9- or 10-membered heterocyclyl ring selected from 7-isoquinolinyl,..2-methyl-3-oxo-2,3-dihydroindazol-6-yl, [1,6]-naphthydrin-3-yl, [1,7]-naphthydrin-2-yl, 1-oxo-2,3-dihydrobenzofuran-4-yl, 3-oxo - 2,3 - dihydrobenzofuran-5-yl, dihydro-benzodioxinyl, 6-quinazolinyl, 2-amino-6-quinazolinyl, 4-methylamino-6-quinazolinyl, 2,4-diamino-6 quinazolinyl, 3-oxo-3,4 - dihydro-1,4-benzoxazin-6-yl, 2,2 - difluoro-l;3-benzodioxol-5-yl and 2,2,3,3 tetrafluoro-2,3-dihydro-l,4-benzodioxin-6-yl, each of which is optionally substituted with one or more substituents selected from halo, haloakyl, C 1-6 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, N-dimethylamino-C 1-6 -alkyl, N-dimethylamino-C 1-6 -alkoxy, amino, alkyl-carbonylamino, morpholino-sulfonyl, amino-sulfonyl, oxazolyl, pyrrolyl, 4 morpholinyl, carboxyl, cyano, and acetyl; wherein R 1 in formula I is selected from unsubstituted or substituted phenyl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl and 11-14 membered tricyclic heterocyclyl, and R 1 in formula II is selected from specific bicyclic heterocycles.

Abstract translation: 本发明提供了可用于治疗血管发生和相关疾病如癌症的化合物类，包括其药学上可接受的衍生物。 式I和II其中R是选自7-异喹啉基，2-甲基-3-氧代-2,3-二氢吲唑-6-基，[1,6] - 萘啶-2-酮的9-或10-元杂环基环， 吡啶-3-基，[1,7]萘啶-2-基，1-氧代-2,3-二氢苯并呋喃-4-基，3-氧代-2,3-二氢 - 二氢苯并二氧杂环戊烯基，6-喹唑啉基，2-氨基-6-喹唑啉基，4-甲基氨基-6-喹唑啉基，2,4-二氨基-6-喹唑啉基，3-氧代-3,4-二氢苯并呋喃-5-基 二氢-1,4-苯并恶嗪-6-基，2,2 - 二氟-1,3-苯并间二氧杂环戊烯-5-基和2,2,3,3-四氟 - 2,3-二氢-1,4-苯并二恶英-6-基，其各自任选被一个或多个选自卤素，卤代烷基，C 1-6烷基，C 1 -C 6烷基， 2-8链烯基，C 2-8炔基，N-二甲基氨基-C 1-6 - 烷基，N-二甲基氨基-C1- 6 - 烷氧基，氨基，烷基 - 羰基氨基，吗啉代 - 磺酰基，氨基 - 磺酰基，恶唑基，吡咯基，吗啉基，羧基，氰基和乙酰基。 其中式I中的R 1选自未取代或取代的苯基，5-6元杂芳基，9-10元双环杂环基和11-14元三环杂环基，R 1， 式Ⅱ中选自具体的双环杂环。

公开(公告)号：WO2004085425A1

公开(公告)日：2004-10-07

申请号：PCT/US2004/008809

申请日：2004-03-22

Applicant: AMGEN INC

Inventor： DIPIETRO, Lucian V. ,  HARMANGE, Jean-Christophe ,  ASKEW, JR., Benny C. ,  ELBAUM, Daniel ,  GERMAIN, Julie ,  HABGOOD, Gregory J. ,  KIM, Joseph L. ,  PATEL, Vinod F. ,  POTASHMAN, Michele ,  VAN DER PLAS, Simon

IPC: C07D401/12

CPC classification number: C07D401/12 ,  C07D235/30 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D487/04

Abstract: The invention relates to compounds of the formulae (I) to (III) wherein the substituents are as defined in the specification. These compounds have kinase inhibitory activity, such as VEGFR/KDR inhibitory activity. Accordingly, the compounds of the formulae (I) to (III) would be useful in the prevention and treatment of angiogenesis related disorders, ophthalmological conditions, proliferative diseases, inflammatory diseases, and other pathological conditions as described in the specification.

Abstract translation: 本发明涉及式（I）至（III）的化合物，其中取代基如说明书中所定义。 这些化合物具有激酶抑制活性，例如VEGFR / KDR抑制活性。 因此，式（I）至（III）的化合物可用于预防和治疗血管发生相关疾病，眼科病症，增殖性疾病，炎性疾病和其他病理状况，如本说明书所述。

公开(公告)号：WO2005073224A2

公开(公告)日：2005-08-11

申请号：PCT/US2005/002304

申请日：2005-01-24

Applicant: AMGEN INC

Inventor： HARMANGE, Jean-Christophe ,  BOOKER, Shon ,  BAUER, David ,  KIM, Tae-Seong ,  CHENG, Yuan ,  XU, Shimin ,  XI, Ning ,  KIM, Joseph, L. ,  TASKER, Andrew

IPC: C07D417/00

CPC classification number: C07D495/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选化合物对于预防和治疗诸如HGF介导的疾病等疾病是有效的。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗疾病和其它疾病或涉及癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：WO2005070891A2

公开(公告)日：2005-08-04

申请号：PCT/US2005/002326

申请日：2005-01-24

Applicant: AMGEN INC

Inventor： POTASHMAN, Michele ,  KIM, Tae-seong ,  BELLON, Steven ,  BOOKER, Shon ,  CHENG, Yuan ,  KIM, Joseph, L. ,  TASKER, Andrew ,  XI, Ning ,  XU, Shimin ,  HARMANGE, Jean-Christophe ,  BORG, George ,  WEISS, Matthew ,  HODOUS, Brian, L. ,  GRACEFFA, Russell ,  BUCKNER, Willian, H. ,  MASSE, Craig, E. ,  CHOQUETTE, Deborah ,  MARTIN, Matthew, W. ,  GERMAIN, Julie ,  DIPIETRO, Lucian, V. ,  CHAFFEE, Stuart, C. ,  NUNES, Joseph, J. ,  BUCHANAN, John, L. ,  HABGOOD, Gregory, J. ,  MCGOWAN, David, C. ,  WHITTINGTON, Douglas, A.

IPC: C07D215/00

CPC classification number: C07D213/64 ,  C07D213/81 ,  C07D215/233 ,  C07D215/38 ,  C07D215/48 ,  C07D215/54 ,  C07D237/34 ,  C07D239/34 ,  C07D239/47 ,  C07D239/84 ,  C07D239/94 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutically compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选化合物对于预防和治疗诸如HGF介导的疾病等疾病是有效的。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗涉及癌症等的疾病和其它疾病或病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：WO2003018022A1

公开(公告)日：2003-03-06

申请号：PCT/US2002/026926

申请日：2002-08-22

Applicant: AMGEN INC.

Inventor： BUCHANAN, John, L. ,  CHAFFEE, Stuart ,  HARMANGE, Jean-Christophe ,  NOVAK, Perry, M. ,  ZHU, Xiaotian

IPC: A61K31/506

CPC classification number: C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

Abstract: Compounds of Formula (I) are claimed, wherein R 1 is a heteroaryl ring containing at least one oxygen of sulfur heteroatom and R 2 is as defined in the claims. These compounds are useful in the treatment of cancer.

Abstract translation: 要求的式（I）化合物，其中R 1是含有至少一个硫杂原子氧的杂芳基环，R 2如权利要求中所定义。 这些化合物可用于治疗癌症。

公开(公告)号：WO2003018021A1

公开(公告)日：2003-03-06

申请号：PCT/US2002/026870

申请日：2002-08-22

Applicant: AMGEN INC.

Inventor： HARMANGE, Jean-Christophe ,  BOOKER, Shon ,  BUCHANAN, John, L. ,  CHAFFEE, Stuart ,  NOVAK, Perry, M. ,  VAN DER PLAS, Simon ,  ZHU, Xiaotian

IPC: A61K31/506

CPC classification number: C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: The invention encompasses compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions, uses and methods for prophylaxis and treatment of cancer.

Abstract translation: 本发明包括其化合物，类似物，前药及其药学上可接受的盐，药物组合物，用途和预防和治疗癌症的方法。

公开(公告)号：WO2008079292A1

公开(公告)日：2008-07-03

申请号：PCT/US2007/026064

申请日：2007-12-19

Applicant: AMGEN INC. ,  CHENG, Yuan ,  CHOQUETTE, Deborah ,  HARMANGE, Jean-Christophe ,  TASKER, Andrew

Inventor： CHENG, Yuan ,  CHOQUETTE, Deborah ,  HARMANGE, Jean-Christophe ,  TASKER, Andrew

IPC: C07D401/06 ,  C07D401/14 ,  C07D417/14 ,  A61K31/4427 ,  A61K31/4725 ,  A61P35/00 ,  A61P29/00

CPC classification number: C07D401/06 ,  C07D401/14 ,  C07D417/14

Abstract: Selected compounds of formula (I) are effective for prophylaxis and treatment of diseases, such as VEGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选择的式（I）化合物可有效预防和治疗诸如VEGF介导的疾病之类的疾病。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗疾病和其它疾病或涉及癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：WO2009143477A1

公开(公告)日：2009-11-26

申请号：PCT/US2009/045058

申请日：2009-05-22

Applicant: AMGEN INC. ,  ALBRECHT, Brian, K. ,  BELLON, Steven ,  BODE, Christiane ,  BOEZIO, Alessandro ,  CHOQUETTE, Deborah ,  HARMANGE, Jean-Christophe

Inventor： ALBRECHT, Brian, K. ,  BELLON, Steven ,  BODE, Christiane ,  BOEZIO, Alessandro ,  CHOQUETTE, Deborah ,  HARMANGE, Jean-Christophe

IPC: C07D471/04 ,  A61K31/4192 ,  A61P35/00

CPC classification number: C07D471/04

Abstract: Selected fused imidazole or triazole derivatives are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 选择的稠合咪唑或三唑衍生物可有效预防和治疗诸如HGF介导的疾病之类的疾病。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗疾病和其它疾病或涉及癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：WO2008079291A2

公开(公告)日：2008-07-03

申请号：PCT/US2007/026063

申请日：2007-12-19

Applicant: AMGEN INC. ,  BELLON, Steven ,  BOOKER, Shon ,  D'ANGELO, Noel ,  FELLOWS, Ingrid, M. ,  HARMANGE, Jean-Christophe ,  KIM, Tae-Seong ,  LEE, Matthew ,  LIU, Longbin ,  NORMAN, Mark, H.

Inventor： BELLON, Steven ,  BOOKER, Shon ,  D'ANGELO, Noel ,  FELLOWS, Ingrid, M. ,  HARMANGE, Jean-Christophe ,  KIM, Tae-Seong ,  LEE, Matthew ,  LIU, Longbin ,  NORMAN, Mark, H.

CPC classification number: C07D401/14 ,  C07D401/12

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as c-met mediated diseases and/or HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 选择的化合物对于预防和治疗诸如c-met介导的疾病和/或HGF介导的疾病的疾病是有效的。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗疾病和其它疾病或涉及癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。