公开(公告)号：WO2015017407A1

公开(公告)日：2015-02-05

申请号：PCT/US2014/048610

申请日：2014-07-29

Applicant: AMGEN INC.

Inventor： LEWIS, Richard T. ,  ALLEN, Jennifer R. ,  BROWN, James ,  GUZMAN-PEREZ, Angel ,  HUA, Zihao ,  JUDD, Ted ,  LIU, Qingyian ,  OLIVIERI, Philip R. ,  SCHENKEL, Laurie ,  STELLWAGEN, John ,  VAIDA, Karina R. ,  WHITE, Ryan

IPC: C07D513/08 ,  C07D519/00 ,  A61K31/547 ,  A61P25/00

CPC classification number: C07D513/08 ,  C07D513/06 ,  C07D519/00

Abstract: The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I, wherein variables A 4 , A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds and the compounds and compositions for treatment of disorders and/ or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions.

Abstract translation: 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式I，其中式I的变量A4，A5，A6，A8，R1，R2，R3，R7和n独立地在本文中定义。 本发明还提供包含化合物的药物组合物和用于治疗由BACE的生物活性产生的A-β斑块形成和沉积相关的病症和/或病症的化合物和组合物。 这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。

公开(公告)号：WO2008124083A3

公开(公告)日：2008-10-16

申请号：PCT/US2008/004432

申请日：2008-04-03

Applicant: AMGEN INC. ,  CEE, Victor, J. ,  DEAK, Holly, L. ,  GEUNS-MEYER, Stephanie, D. ,  DU, Bingfan ,  HODOUS, Brian, L. ,  MARTIN, Mathew, W. ,  NGUYEN, Hanh, Nho ,  OLIVIERI, Philip, R. ,  PANTER, Kathleen ,  ROMERO, Karina ,  SCHENKEL, Laurie ,  WHITE, Ryan

Inventor： CEE, Victor, J. ,  DEAK, Holly, L. ,  GEUNS-MEYER, Stephanie, D. ,  DU, Bingfan ,  HODOUS, Brian, L. ,  MARTIN, Mathew, W. ,  NGUYEN, Hanh, Nho ,  OLIVIERI, Philip, R. ,  PANTER, Kathleen ,  ROMERO, Karina ,  SCHENKEL, Laurie ,  WHITE, Ryan

IPC: C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D409/04 ,  C07D471/04 ,  C07D487/04 ,  C07D493/04 ,  C07D495/04 ,  A61K31/502 ,  A61P35/00

Abstract: The present invention relates to chemical compounds having a general formula (I), wherein A 1-8 , D , , L 1 , L 2 , R 1 , R 6-8 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.

公开(公告)号：WO2014059185A1

公开(公告)日：2014-04-17

申请号：PCT/US2013/064400

申请日：2013-10-10

Applicant: AMGEN INC.

Inventor： LEWIS, Richard T. ,  CHOQUETTE, Deborah ,  EPSTEIN, Oleg ,  GUZMAN-PEREZ, Angel ,  HUA, Zihao ,  HUMAN, Jason Brooks ,  JUDD, Ted ,  LIU, Qingyian ,  LOPEZ, Patricia ,  MINATTI, Ana Elena ,  OLIVIERI, Philip R. ,  ROMERO, Karina ,  SCHENKEL, Laurie ,  STELLWAGEN, John ,  WHITE, Ryan ,  ZHENG, Xiao Mei ,  ALLEN, Jennifer R. ,  CHENG, Yuan ,  HARRINGTON, Paul E. ,  HUNGATE, Randall W. ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  XUE, Qiufen ,  ZHONG, Wenge

IPC: C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  C07D279/12 ,  C07D279/14 ,  C07D513/04 ,  C07D513/10 ,  C07D519/00 ,  A61P25/18 ,  A61P25/28 ,  A61K31/54 ,  A61K31/541 ,  A61K31/547

CPC classification number: C07D279/12 ,  C07D213/79 ,  C07D239/74 ,  C07D241/44 ,  C07D279/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  C07D513/10 ,  C07D519/00

Abstract: The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 4 , A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.

Abstract translation: 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式I：其中式I的变量A4，A5，A6，A8，R1，R2，R3，R7和n独立地在本文中定义。 本发明还提供包含该化合物的药物组合物，以及用于治疗由BACE的生物学活性产生的A-β斑块形成和沉积相关的病症和/或病症的化合物和组合物的相应用途。 这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。 本发明还提供式II化合物及其次级实施方案，可用于制备式I-II化合物的中间体和方法和方法。

公开(公告)号：WO2015051043A1

公开(公告)日：2015-04-09

申请号：PCT/US2014/058699

申请日：2014-10-01

Applicant: AMGEN INC.

Inventor： BREGMAN, Howard ,  CHAKKA, Nagasree ,  DIMAURO, Erin F. ,  GAO, Hua ,  GUNAYDIN, Hakan ,  HUANG, Hongbing ,  OLIVIERI, Philip ,  SCHENKEL, Laurie ,  WEISS, Matthew

IPC: C07D213/64 ,  A61K31/4418 ,  A61P25/04

CPC classification number: C07D417/12 ,  C07D213/26 ,  C07D213/64 ,  C07D213/643 ,  C07D213/70 ,  C07D401/04 ,  C07D405/12

Abstract: The present invention provides compounds of Formula (Ia), and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of voltage-gated sodium channels, in particular Nav 1.7. (Ia); as described in the specification. 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, as well as intermediates and processes useful for making the compounds.

Abstract translation: 本发明提供式（Ia）化合物及其药学上可接受的盐。 该化合物可用作电压门控钠通道的抑制剂，特别是Nav 1.7。 式（Ia）; 如说明书中所述。 该化合物可用于治疗可通过抑制钠通道（例如疼痛障碍）治疗的疾病。 还提供了含有本发明化合物的药物组合物，以及可用于制备化合物的中间体和方法。

公开(公告)号：WO2007087276A1

公开(公告)日：2007-08-02

申请号：PCT/US2007/001714

申请日：2007-01-22

Applicant: AMGEN INC. ,  CEE, Victor J. ,  DEAK, Holly L. ,  DU, Bingfan ,  GEUNS-MEYER, Stephanie D. ,  HODOUS, Brian L. ,  NGUYEN, Hanh Nho ,  OLIVIERI, Philip R. ,  PATEL, Vinod F. ,  ROMERO, Karina ,  SCHENKEL, Laurie

Inventor： CEE, Victor J. ,  DEAK, Holly L. ,  DU, Bingfan ,  GEUNS-MEYER, Stephanie D. ,  HODOUS, Brian L. ,  NGUYEN, Hanh Nho ,  OLIVIERI, Philip R. ,  PATEL, Vinod F. ,  ROMERO, Karina ,  SCHENKEL, Laurie

IPC: C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D497/04 ,  A61K31/502 ,  A61P35/00

CPC classification number: C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D497/04

Abstract: The present invention relates to chemical compounds having a general formula (I) wherein A 1 , A 2 , C 1 , C 2 , D, L 1 , L 2 , Z and R 1-8 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.

Abstract translation: 本发明涉及具有通式（I）的化合物，其中A 1，A 2，C 1，C 2 D，L 1，L 2，Z和R 1-8均在本文中定义，合成中间体是 能够调节各种蛋白激酶受体酶，从而影响与这些激酶的活性相关的各种疾病状态和状况。 例如，化合物能够调节Aurora激酶，从而影响细胞周期和细胞增殖的过程，以治疗癌症和与癌症有关的疾病。 本发明还包括药物组合物，包括该化合物，以及治疗与Aurora激酶活性有关的疾病状态的方法。

公开(公告)号：WO2014120658A1

公开(公告)日：2014-08-07

申请号：PCT/US2014/013340

申请日：2014-01-28

Applicant: AMGEN INC.

Inventor： WHITE, Ryan ,  ALLEN, Jennifer R. ,  EPSTEIN, Oleg ,  HONG, Fang-Tsao ,  HUA, Zihao ,  HUMAN, Jason Brooks ,  LOPEZ, Patricia ,  OLIVIERI, Philip R. ,  ROMERO, Karina ,  SCHENKEL, Laurie ,  STELLWAGEN, John ,  TAMAYO, Nuria A. ,  ZHENG, Xiao Mei

IPC: C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  C07D513/10 ,  C07D513/14 ,  C07D513/20 ,  C07D519/00 ,  A61K31/5415 ,  A61K31/542 ,  A61K31/547 ,  A61K31/55 ,  A61P25/00 ,  A61P25/28

CPC classification number: C07D513/04 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/10 ,  C07D513/14 ,  C07D513/20 ,  C07D519/00

Abstract: The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 , X, Y, n and o of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.

Abstract translation: 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式I：其中式I的变量A5，A6，A8，R1，R2，R3，R7，X，Y，n和o独立地在本文中定义。 本发明还提供包含该化合物的药物组合物，以及用于治疗由BACE的生物学活性产生的A-β斑块形成和沉积相关的病症和/或病症的化合物和组合物的相应用途。 这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。 本发明进一步提供式II化合物及其分式实施方案，式III化合物，可用于制备式I-III化合物及其分式的中间体和方法和方法。

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：WO2009155121A2

公开(公告)日：2009-12-23

申请号：PCT/US2009/045713

申请日：2009-05-29

Applicant: AMGEN INC. ,  BO, Yunxin Y. ,  BOOKER, Shon ,  BRYAN, Marian ,  DEAK, Holly L. ,  LIU, Longbin ,  ANDREWS, Kristin ,  NISHIMURA, Nobuko ,  NORMAN, Mark H. ,  PANTER, Kathleen ,  SCHENKEL, Laurie ,  SIEGMUND, Aaron C. ,  TAMAYO, Nuria A. ,  YANG, Kevin

Inventor： BO, Yunxin Y. ,  BOOKER, Shon ,  BRYAN, Marian ,  DEAK, Holly L. ,  LIU, Longbin ,  ANDREWS, Kristin ,  NISHIMURA, Nobuko ,  NORMAN, Mark H. ,  PANTER, Kathleen ,  SCHENKEL, Laurie ,  SIEGMUND, Aaron C. ,  TAMAYO, Nuria A. ,  YANG, Kevin

IPC: C07D401/04 ,  C07D401/14 ,  C07D471/04 ,  A61K31/498 ,  A61K31/502 ,  A61K31/4709 ,  A61P35/00

CPC classification number: C07D401/04 ,  C07D401/14 ,  C07D471/04

Abstract: The present invention relates to compounds of Formula (I), or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein Q, X 1 , X 2 , R 1 and Z are as defined herein.

Abstract translation: 本发明涉及式（I）化合物或其药学上可接受的盐; 使用该化合物治疗疾病或病症如癌症的方法; 和含有化合物的药物组合物，其中Q，X 1，X 2，R 1和Z如本文所定义。