公开(公告)号：WO2007061670A1

公开(公告)日：2007-05-31

申请号：PCT/US2006/044058

申请日：2006-11-13

Applicant: AMGEN INC. ,  ZHONG, Wenge ,  HITCHCOCK, Stephen ,  ALBRECHT, Brian K ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HICKMAN, Dean ,  HORNE, Daniel ,  HUNGATE, Randall ,  JUDD, Ted ,  KALLER, Matthew ,  KREIMAN, Charles ,  LA, Daniel ,  LOPEZ, Patricia ,  MASSE, Craig E. ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  NIXEY, Thomas ,  PATEL, Vinod F. ,  PENNINGTON, Lewis ,  WEISS, Matthew ,  XUE, Qiufen ,  YANG, Bryant

Inventor： ZHONG, Wenge ,  HITCHCOCK, Stephen ,  ALBRECHT, Brian K ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HICKMAN, Dean ,  HORNE, Daniel ,  HUNGATE, Randall ,  JUDD, Ted ,  KALLER, Matthew ,  KREIMAN, Charles ,  LA, Daniel ,  LOPEZ, Patricia ,  MASSE, Craig E. ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  NIXEY, Thomas ,  PATEL, Vinod F. ,  PENNINGTON, Lewis ,  WEISS, Matthew ,  XUE, Qiufen ,  YANG, Bryant

IPC: C07D405/12 ,  C07D413/12 ,  A61K31/44 ,  A61P25/28

CPC classification number: C07D405/12 ,  C07D311/68 ,  C07D413/12 ,  C07D491/052

Abstract: The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I); wherein A, B, W, R 3 , R 4 , R 5 , i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula (I), methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula (I), or compositions including them, to a subject. The invention also comprises further embodiments of Formulas (II) and (III), intermediates and processes useful for the preparation of compounds of the invention.

Abstract translation: 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式（I）; 其中A，B，W，R 3，R 4，R 5，i和j在本文中定义。 本发明还包括药物组合物，其包括一种或多种式（I）化合物，这些化合物的使用方法，包括治疗AD和相关疾病，通过施用式（I）化合物或其组合物，包括它们， 到一个主题。 本发明还包括式（II）和（III）的其它实施方案，可用于制备本发明化合物的中间体和方法。

公开(公告)号：WO2013086229A1

公开(公告)日：2013-06-13

申请号：PCT/US2012/068297

申请日：2012-12-06

Applicant: AMGEN INC.

Inventor： BOEZIO, Christiane ,  BREGMAN, Howard ,  COATS, James, R. ,  DIMAURO, Erin, F. ,  DINEEN, Thomas ,  DU, Bingfan ,  GRACEFFA, Russell ,  KREIMAN, Charles ,  LA, Daniel ,  MARX, Isaac, E. ,  CHAKKA, Nagasree ,  NGUYEN, Hanh Nho ,  PETERSON, Emily, Anne ,  WEISS, Matthew ,  COPELAND, Katrina, W. ,  DEAK, Holly, L. ,  BOEZIO, Alessandro

IPC: C07D239/42 ,  C07D277/52 ,  C07D285/08 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  A61K31/427

CPC classification number: C07D498/04 ,  C07D239/42 ,  C07D277/52 ,  C07D285/08 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

Abstract: The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. (The Formula I should be inserted here.) The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

Abstract translation: 本发明提供式I化合物或其药学上可接受的盐，其是电压门控钠通道的抑制剂，特别是Nav 1.7。 （此处应插入式I）。该化合物可用于治疗通过抑制钠通道（如疼痛障碍）治疗的疾病。 还提供含有本发明化合物的药物组合物。

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：WO2006039718A3

公开(公告)日：2006-04-13

申请号：PCT/US2005/035873

申请日：2005-10-03

Applicant: AMGEN INC

Inventor： PATEL, Vinod F. ,  KIM, Joseph L. ,  GEUNS-MEYER, Stephanie D. ,  CHAFFEE, Stuart C. ,  CEE, Victor J. ,  HODOUS, Brian L. ,  BELLON, Steven ,  HARMANGE, Jean-christophe ,  OLIVIERI, Philip R. ,  THAMAN, Maya C. ,  DIMAURO, Erin F. ,  BUCHANAN, John L. ,  MCGOWAN, David C. ,  ALBRECHT, Brian K. ,  DEAK, Holly L. ,  BEMIS, Jean E. ,  WHITE, Ryan ,  MARTIN, Matthew W. ,  HABGOOD, Gregory J. ,  TEMPEST, Paul A. ,  MASSE, Craig E. ,  BUCKNER, William H. ,  HERBERICH, Bradley J. ,  GRACEFFA, Russell ,  ZHANG, Dawei ,  XU, Shimin ,  SHAM, Kelvin ,  RZASA, Robert M. ,  FALSEY, James Richard ,  CHAKRABARTI, Partha P. ,  CAO, Guo-qiang ,  TOMLINSON, Susan Ann ,  PETTUS, Liping H. ,  SMITH, Adrian Leonard ,  PARAS, Nick A. ,  LIU, Gang ,  DEMORIN, Frenel F. ,  TASKER, Andrew ,  REED, Anthony

IPC: C07D239/84 ,  C07D239/95 ,  C07D401/12 ,  C07D409/04 ,  C07D405/12 ,  C07D409/14 ,  C07D405/04 ,  C07D403/10 ,  C07D401/04 ,  C07D471/04 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D409/12 ,  C07D215/12

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I, wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

公开(公告)号：WO2020036940A1

公开(公告)日：2020-02-20

申请号：PCT/US2019/046319

申请日：2019-08-13

Applicant: AMGEN INC. ,  CARMOT THERAPEUTICS, INC.

Inventor： BUTLER, John R. ,  ERLANSON, Daniel ,  GRACEFFA, Russell ,  IWIG, Jeffrey ,  JEONG, Joon Won ,  WHITE, Ryan D. ,  WU, Yongwei ,  YI, Shuyan ,  BANERJEE, Abhisek ,  MCFARLAND, Jesse M. ,  ZHENG, Xiao Mei

IPC: C07D487/08 ,  A61K31/407 ,  A61P25/00 ,  A61K31/403

Abstract: The present invention provides a compound of formula (I) or a pharmacuetically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.

公开(公告)号：WO2009064418A1

公开(公告)日：2009-05-22

申请号：PCT/US2008/012717

申请日：2008-11-12

Applicant: AMGEN INC. ,  GRACEFFA, Russell ,  KALLER, Matthew ,  LA, Daniel ,  LOPEZ, Patricia ,  PATEL, Vinod F. ,  ZHONG, Wenge

Inventor： GRACEFFA, Russell ,  KALLER, Matthew ,  LA, Daniel ,  LOPEZ, Patricia ,  PATEL, Vinod F. ,  ZHONG, Wenge

IPC: C07D491/04 ,  C07D309/28 ,  C07D493/10 ,  C07D215/38 ,  C07D519/00 ,  C07D487/04 ,  C07D403/12 ,  C07D401/12 ,  C07D417/12 ,  A61K31/436 ,  A61K31/352 ,  A61K31/35 ,  A61P25/28

CPC classification number: C07D519/00 ,  C07D221/20 ,  C07D311/96 ,  C07D317/46 ,  C07D317/58 ,  C07D317/62 ,  C07D405/12 ,  C07D413/06 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D491/052 ,  C07D491/107 ,  C07D493/10

Abstract: The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I) I wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , X and Z are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions. The invention also comprises further embodiments of Formula II, intermediates and processes useful for the preparation of compounds of Formulas I and II.

Abstract translation: 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式（I）I，其中R1，R2，R3，R4，R5，A1，A2，A3，A4，X和Z如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的疾病和病症的用途。 这些疾病包括例如阿尔茨海默病（AD），认知缺陷和损伤，精神分裂症和其他类似的中枢神经系统疾病。 本发明还包括式II的其它实施方案，可用于制备式I和II化合物的中间体和方法。

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：WO2019055590A1

公开(公告)日：2019-03-21

申请号：PCT/US2018/050793

申请日：2018-09-13

Applicant: AMGEN INC. ,  CYTOKINETICS, INC.

Inventor： ASHCRAFT, Luke ,  BOEZIO, Alessandro ,  BUTLER, John ,  CHANDRA, Aroop ,  CHUANG, Chihyuan ,  COLLIBEE, Scott, E. ,  DEBENEDETTO, Mikkel ,  DIMASSA, Vincent ,  GRACEFFA, Russell ,  MALINOWSKI, Justin ,  MOEBIUS, David ,  MORGAN, Bradley, P. ,  PAYETTE, Joshua ,  ROMERO, Antonio ,  ST. JEAN, David, Jr. ,  VARGAS, Richard ,  YEOMAN, John ,  ZHANG, Hanmo ,  CHENG, Alan ,  GONZALEZ LOPEZ DE TURISO, Felix ,  JOHNSON, Michael Garrett

IPC: C07D403/12 ,  C07D401/14 ,  C07D413/14 ,  C07D401/06 ,  C07D403/14 ,  C07D405/12 ,  C07D413/12 ,  C07D417/14 ,  C07D207/16 ,  C07D209/02

Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.

公开(公告)号：WO2007062007A1

公开(公告)日：2007-05-31

申请号：PCT/US2006/045004

申请日：2006-11-20

Applicant: AMGEN INC. ,  ALBRECHT, Brian, K ,  ANDERSEN, Denise, Lyn ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart, C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  HUNGATE, Randall ,  JUDD, Ted ,  KALLER, Matthew ,  KREIMAN, Charles ,  LA, Daniel ,  LOPEZ, Patricia ,  MASSE, Craig, E. ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  NIXEY, Thomas ,  PATEL, Vinod, F. ,  PENNINGTON, Lewis ,  WEISS, Matthew ,  XUE, Qiufen ,  YANG, Bryant ,  ZHONG, Wenge

Inventor： ALBRECHT, Brian, K ,  ANDERSEN, Denise, Lyn ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart, C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  HUNGATE, Randall ,  JUDD, Ted ,  KALLER, Matthew ,  KREIMAN, Charles ,  LA, Daniel ,  LOPEZ, Patricia ,  MASSE, Craig, E. ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  NIXEY, Thomas ,  PATEL, Vinod, F. ,  PENNINGTON, Lewis ,  WEISS, Matthew ,  XUE, Qiufen ,  YANG, Bryant ,  ZHONG, Wenge

IPC: C07D405/12 ,  C07D413/12 ,  A61K31/44 ,  A61P25/28

CPC classification number: C07D405/12 ,  C07D413/12

Abstract: The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A, B, R 3 , R 4 , R 5 , i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula I, or compositions including them, to a subject. The invention also comprises further embodiments of Formulas II and III, intermediates and processes useful for the preparation of compounds of the invention.

Abstract translation: 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中A，B，R 3，R 4，R 5，i和j分别为 本文定义。 本发明还包括药物组合物，其包括一种或多种式I化合物，这些化合物的使用方法，包括治疗AD和相关疾病，通过给受试者施用式I化合物或包含它们的组合物。 本发明还包括式II和III的其它实施方案，可用于制备本发明化合物的中间体和方法。

公开(公告)号：WO2007048070A2

公开(公告)日：2007-04-26

申请号：PCT/US2006/041562

申请日：2006-10-23

Applicant: AMGEN INC. ,  GERMAIN, Julie ,  ASKEW, Benny, C., Jr. ,  BAUER, David ,  CHOQUETTE, Deborah ,  DIPIETRO, Lucian, V. ,  GRACEFFA, Russell ,  HARMANAGE, Jean-Christophe ,  HUANG, Qi ,  KIM, Joseph, L. ,  LA, Daniel ,  LI, Aiwen ,  NISHIMURA, Nobuko ,  NOMACK, Rana ,  PATEL, Vinod ,  POTASHMAN, Michele ,  RIAHI, Babak ,  STORZ, Thomas ,  VAN DER PLAS, Simon ,  YANG, Kevin ,  YUAN, Chester, C.

Inventor： GERMAIN, Julie ,  ASKEW, Benny, C., Jr. ,  BAUER, David ,  CHOQUETTE, Deborah ,  DIPIETRO, Lucian, V. ,  GRACEFFA, Russell ,  HARMANAGE, Jean-Christophe ,  HUANG, Qi ,  KIM, Joseph, L. ,  LA, Daniel ,  LI, Aiwen ,  NISHIMURA, Nobuko ,  NOMACK, Rana ,  PATEL, Vinod ,  POTASHMAN, Michele ,  RIAHI, Babak ,  STORZ, Thomas ,  VAN DER PLAS, Simon ,  YANG, Kevin ,  YUAN, Chester, C.

IPC: C07D471/04 ,  A61K31/437 ,  A61P35/00

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis 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血管生成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。