公开(公告)号：WO2012078777A1

公开(公告)日：2012-06-14

申请号：PCT/US2011/063776

申请日：2011-12-07

Applicant: AMGEN INC. ,  WANG, Hui-Ling ,  BISWAS, Kaustav ,  CEE, Victor J. ,  CHAVEZ JR., Frank ,  HERBERICH, Bradley ,  JACKSON, Claire L.M. ,  LEE, Matthew ,  NIXEY, Thomas ,  PETTUS, Liping H. ,  REED, Anthony B. ,  RZASA, Robert M. ,  RUMFELT, Shannon ,  TASKER, Andrew ,  WU, Bin ,  WURZ, Ryan

Inventor： WANG, Hui-Ling ,  BISWAS, Kaustav ,  CEE, Victor J. ,  CHAVEZ JR., Frank ,  HERBERICH, Bradley ,  JACKSON, Claire L.M. ,  LEE, Matthew ,  NIXEY, Thomas ,  PETTUS, Liping H. ,  REED, Anthony B. ,  RZASA, Robert M. ,  RUMFELT, Shannon ,  TASKER, Andrew ,  WU, Bin ,  WURZ, Ryan

IPC: C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  C07D491/107 ,  A61K31/497 ,  A61K31/437 ,  A61K31/506 ,  A61K31/444 ,  A61K31/4709

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

Abstract: The invention relates to bicyclic compounds of formula (1'), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

Abstract translation: 本发明涉及式（1'）的双环化合物及其盐。 在一些实施方案中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。 在另外的实施方案中，本发明涉及包含本文公开的化合物的药物组合物及其在预防和治疗Pim激酶相关病症和疾病，优选癌症中的用途。

公开(公告)号：WO2009154780A1

公开(公告)日：2009-12-23

申请号：PCT/US2009/003673

申请日：2009-06-18

Applicant: AMGEN INC. ,  EPIX PHARMACEUTICALS ,  CEE, Victor, J. ,  LIN, Jian ,  YU, Xiang, Y. ,  ZHANG, Zhaoda

Inventor： CEE, Victor, J. ,  LIN, Jian ,  YU, Xiang, Y. ,  ZHANG, Zhaoda

IPC: C07D307/78 ,  C07D405/04 ,  C07D405/10 ,  C07D409/10 ,  A61K31/343 ,  A61K31/397 ,  A61P25/00

CPC classification number: C07D513/04 ,  A61K9/2018 ,  A61K9/2059 ,  A61K9/48

Abstract: The present invention relates to compounds of Formula (I) that are have activity as S1P receptor modulating agents, more specifically to specifically compounds that are S1P1 receptor agonists. The invention also related to the use of such compounds to treat diseases associated with inappropriate S1P1 receptor activity such as autoimmune diseases.

Abstract translation: 本发明涉及具有作为S1P受体调节剂的活性的式（I）化合物，更具体地涉及作为S1P1受体激动剂的具体化合物。 本发明还涉及使用这些化合物来治疗与不适当的S1P1受体活性相关的疾病，例如自身免疫性疾病。

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：WO2008124083A2

公开(公告)日：2008-10-16

申请号：PCT/US2008004432

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

CPC classification number: C07D471/04 ,  C07D401/12 ,  C07D401/14 ,  C07D487/04 ,  C07D493/04 ,  C07D495/04

Abstract: The present invention relates to chemical compounds having a general formula I {INSERT STRUCTURE HERE} 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.

Abstract translation: 本发明涉及具有通式I {INSERT STRUCTURE HERE}的化合物，其中A 1-8，D，O，L 1， L 2，R 1，R 6〜8和n如本文所定义，合成中间体能够调节各种蛋白激酶受体 酶，从而影响与这种激酶的活性相关的各种疾病状态和病症。 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：WO2007100646A1

公开(公告)日：2007-09-07

申请号：PCT/US2007/004700

申请日：2007-02-22

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

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

IPC: C07D401/14 ,  C07D417/14 ,  C07D413/14 ,  C07D403/12 ,  A61K31/444 ,  A61K31/4427 ,  A61K31/506 ,  A61P35/00

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

Abstract: The present invention relates to chemical compounds having a general formula I "INSERT STRUCTURE HERE" wherein A, B, C 1 , C 2 , D, L 1 , L 2 and R 3-4 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 Tie-2 and Aurora kinase enzymes thereby influencing angiogenesis and the process of cell cycle and cell proliferation, respectively, 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 various protein kinases.

Abstract translation: 本发明涉及具有通式I“INSERT STRUCTURE HERE”的化合物，其中A，B，C 1，C 2，D，L 1， / SUP>，L 2和R 3〜4以及合成中间体，其能够调节各种蛋白激酶受体酶，从而影响各种疾病 与这种激酶的活动相关的状态和条件。 例如，这些化合物能够调节Tie-2和Aurora激酶，从而分别影响血管生成和细胞周期和细胞增殖过程，以治疗癌症和癌症相关疾病。 本发明还包括药物组合物，包括该化合物，以及治疗与各种蛋白激酶活性有关的疾病状态的方法。

公开(公告)号：WO2006044823A3

公开(公告)日：2006-06-15

申请号：PCT/US2005037299

申请日：2005-10-17

Applicant: AMGEN INC ,  CHAFFEE STUART C ,  ALBRECHT BRIAN K ,  HODOUS BRIAN L ,  MARTIN MATTHEW W ,  MCGOWAN DAVID C ,  DIMAURO ERIN F ,  REDDY GADE ,  CEE VICTOR J ,  OLIVIERI PHILIP R ,  REED ANTHONY ,  ROMERO KARINA

Inventor： CHAFFEE STUART C ,  ALBRECHT BRIAN K ,  HODOUS BRIAN L ,  MARTIN MATTHEW W ,  MCGOWAN DAVID C ,  DIMAURO ERIN F ,  REDDY GADE ,  CEE VICTOR J ,  OLIVIERI PHILIP R ,  REED ANTHONY ,  ROMERO KARINA

IPC: C07D239/42 ,  A61K31/505 ,  A61P35/00

CPC classification number: C07D213/74 ,  C07D213/81 ,  C07D215/14 ,  C07D239/42 ,  C07D241/42 ,  C07D401/06 ,  C07D401/12 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D409/06 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04

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, A4, R1 and R2 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.

Abstract translation: 本发明包括用于预防和治疗蛋白激酶介导的疾病，包括炎症，癌症和相关病症的一类新化合物。 该化合物具有通式I：其中A1，A2，A3，A4，R1和R2如本文所定义。 因此，本发明还包括含有本发明化合物的药物组合物，使用本发明化合物和组合物预防和治疗激酶介导疾病的方法，以及可用于制备本发明化合物的中间体和方法。

公开(公告)号：WO2005113494A2

公开(公告)日：2005-12-01

申请号：PCT/US2005/016346

申请日：2005-05-09

Applicant: AMGEN INC. ,  GEUNS-MEYER, Stephanie, D. ,  HODOUS, Brian, L. ,  CHAFFEE, Stuart, C. ,  TEMPEST, Paul, A. ,  OLIVIERI, Philip, R. ,  JOHNSON, Rebecca, E. ,  ALBRECHT, Brian, K. ,  PATEL, Vinod, F. ,  CEE, Victor, J. ,  KIM, Joseph, L. ,  BELLON, Steven ,  ZHU, Xiaotian ,  CHENG, Yuan ,  XI, Ning ,  ROMERO, Karina ,  NGUYEN, Hanh, Nho ,  DEAK, Holly, L.

Inventor： GEUNS-MEYER, Stephanie, D. ,  HODOUS, Brian, L. ,  CHAFFEE, Stuart, C. ,  TEMPEST, Paul, A. ,  OLIVIERI, Philip, R. ,  JOHNSON, Rebecca, E. ,  ALBRECHT, Brian, K. ,  PATEL, Vinod, F. ,  CEE, Victor, J. ,  KIM, Joseph, L. ,  BELLON, Steven ,  ZHU, Xiaotian ,  CHENG, Yuan ,  XI, Ning ,  ROMERO, Karina ,  NGUYEN, Hanh, Nho ,  DEAK, Holly, L.

IPC: C07D1/04

CPC classification number: C07D213/73 ,  C07D239/42 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04

Abstract: The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, H 1-5 and R 1-4 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 these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Abstract translation: 本发明涉及具有通式I的化合物，其中A，B，D，E，G，H 1-5和R 1-4如本文所定义，以及合成中间体，其能够调节各种 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，这些化合物能够调节激酶，从而影响血管生成过程并治疗血管生成相关疾病和其它包括癌症和炎症的复发性疾病。 本发明还包括药物组合物，包括该化合物，以及治疗与蛋白激酶活性有关的疾病状态的方法。

公开(公告)号：WO2010126895A1

公开(公告)日：2010-11-04

申请号：PCT/US2010/032593

申请日：2010-04-27

Applicant: AMGEN INC. ,  ANDREWS, Kristin ,  BO, Yunxin, Y. ,  BOOKER, Shon ,  CEE, Victor, J. ,  D'ANGELO, Noel ,  HERBERICH, Bradley, J. ,  HONG, Fang-Tsao ,  JACKSON, Claire, L., M. ,  LANMAN, Brian, A. ,  LIAO, Hongyu ,  LIU, Longbin ,  NISHIMURA, Nobuko ,  NORMAN, Mark, H. ,  PETTUS, Liping, H. ,  REED, Anthony, B. ,  SMITH, Adrian, L. ,  TADESSE, Seifu ,  TAMAYO, Nuria, A. ,  WU, Bin ,  WURZ, Ryan ,  YANG, Kevin

Inventor： ANDREWS, Kristin ,  BO, Yunxin, Y. ,  BOOKER, Shon ,  CEE, Victor, J. ,  D'ANGELO, Noel ,  HERBERICH, Bradley, J. ,  HONG, Fang-Tsao ,  JACKSON, Claire, L., M. ,  LANMAN, Brian, A. ,  LIAO, Hongyu ,  LIU, Longbin ,  NISHIMURA, Nobuko ,  NORMAN, Mark, H. ,  PETTUS, Liping, H. ,  REED, Anthony, B. ,  SMITH, Adrian, L. ,  TADESSE, Seifu ,  TAMAYO, Nuria, A. ,  WU, Bin ,  WURZ, Ryan ,  YANG, Kevin

IPC: C07D401/14 ,  C07D473/00 ,  A61K31/52 ,  A61P35/00

CPC classification number: C07D473/00 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

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 the variables 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; 和含有这些化合物的药物组合物，其中变量如本文所定义。

公开(公告)号：WO2006044823A2

公开(公告)日：2006-04-27

申请号：PCT/US2005/037299

申请日：2005-10-17

Applicant: AMGEN INC. ,  CHAFFEE, Stuart C. ,  ALBRECHT, Brian K. ,  HODOUS, Brian L. ,  MARTIN, Matthew W. ,  MCGOWAN, David C. ,  DIMAURO, Erin F. ,  REDDY, Gade ,  CEE, Victor J. ,  OLIVIERI, Philip R. ,  REED, Anthony ,  ROMERO, Karina

Inventor： CHAFFEE, Stuart C. ,  ALBRECHT, Brian K. ,  HODOUS, Brian L. ,  MARTIN, Matthew W. ,  MCGOWAN, David C. ,  DIMAURO, Erin F. ,  REDDY, Gade ,  CEE, Victor J. ,  OLIVIERI, Philip R. ,  REED, Anthony ,  ROMERO, Karina

IPC: C07D239/42 ,  A61K31/505 ,  A61P35/00

CPC classification number: C07D213/74 ,  C07D213/81 ,  C07D215/14 ,  C07D239/42 ,  C07D241/42 ,  C07D401/06 ,  C07D401/12 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D409/06 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04

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, A4, R1 and R2 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.

Abstract translation: 本发明包括一类新的可用于预防和治疗蛋白激酶介导的疾病，包括炎症，癌症和相关病症的化合物。 化合物具有通式I：其中A1，A2，A3，A4，R1和R2如本文所定义。 因此，本发明还包括含有本发明化合物的药物组合物，使用本发明化合物和组合物预防和治疗激酶介导的疾病的方法，以及可用于制备本发明化合物的中间体和方法。

公开(公告)号：WO2005113494A3

公开(公告)日：2006-03-16

申请号：PCT/US2005016346

申请日：2005-05-09

Applicant: AMGEN INC ,  GEUNS-MEYER STEPHANIE D ,  HODOUS BRIAN L ,  CHAFFEE STUART C ,  TEMPEST PAUL A ,  OLIVIERI PHILIP R ,  JOHNSON REBECCA E ,  ALBRECHT BRIAN K ,  PATEL VINOD F ,  CEE VICTOR J ,  KIM JOSEPH L ,  BELLON STEVEN ,  ZHU XIAOTIAN ,  CHENG YUAN ,  XI NING ,  ROMERO KARINA ,  NGUYEN HANH NHO ,  DEAK HOLLY L

Inventor： GEUNS-MEYER STEPHANIE D ,  HODOUS BRIAN L ,  CHAFFEE STUART C ,  TEMPEST PAUL A ,  OLIVIERI PHILIP R ,  JOHNSON REBECCA E ,  ALBRECHT BRIAN K ,  PATEL VINOD F ,  CEE VICTOR J ,  KIM JOSEPH L ,  BELLON STEVEN ,  ZHU XIAOTIAN ,  CHENG YUAN ,  XI NING ,  ROMERO KARINA ,  NGUYEN HANH NHO ,  DEAK HOLLY L

IPC: C07D401/04 ,  A61K31/4427 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/506 ,  A61K31/53 ,  C07D213/73 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04

CPC classification number: C07D213/73 ,  C07D239/42 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04

Abstract: The present invention relates to chemical compounds having a general formula (I) wherein A, B, D, E, G, H

Abstract translation: 本发明涉及具有通式（I）的化合物，其中A，B，D，E，G，H