公开(公告)号：EP1928844B1

公开(公告)日：2014-04-23

申请号：EP06824821.0

申请日：2006-08-15

申请人： Amgen, Inc

发明人： DIMAURO, Erin F. ,  BEMIS, Jean E. ,  CHAFFEE, Stuart ,  CHEN, Ning ,  HU, Essa ,  KUNZ, Roxanne ,  MARTIN, Matthew W. ,  MCGOWAN, David C. ,  RUMFELT, Shannon

IPC分类号： C07D239/48

CPC分类号： C07D213/75 ,  C07D215/38 ,  C07D239/42 ,  C07D239/48 ,  C07D239/50 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04

公开(公告)号：EP2820014A1

公开(公告)日：2015-01-07

申请号：EP13709033.8

申请日：2013-02-28

申请人： Amgen Inc.

发明人： ALLEN, Jennifer R. ,  AMEGADZIE, Albert ,  ANDREWS, Kristin L. ,  BROWN, James ,  CHEN, Jian J. ,  CHEN, Ning ,  HARRINGTON, Essa Hu ,  LIU, Qingyian ,  NGUYEN, Thomas T. ,  PICKRELL, Alexander J. ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  YUAN, Chester Chenguang ,  ZHONG, Wenge

IPC分类号： C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D473/30 ,  C07D473/34 ,  C07D473/40 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  A61K31/437 ,  A61P25/18

CPC分类号： C07D487/04 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D473/30 ,  C07D473/34 ,  C07D473/40 ,  C07D498/04 ,  C07D513/04 ,  C07D519/00

摘要： Heterobicyclic compounds of Formula (I): (I); or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.

公开(公告)号：EP2376455A1

公开(公告)日：2011-10-19

申请号：EP09793422.8

申请日：2009-12-16

申请人： Amgen Inc.

发明人： ALLEN, Jennifer R. ,  CHEN, Ning ,  FALSEY, James R. ,  FROHN, Michael ,  HARRINGTON, Paul ,  HU, Essa ,  KALLER, Matthew R. ,  KUNZ, Roxanne ,  MERCEDE, Stephanie J. ,  NGUYEN, Thomas T. ,  PICKRELL, Alexander J. ,  REICHELT, Andreas ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  SHAM, Kelvin ,  SIEGMUND, Aaron C. ,  TEGLEY, Christopher M. ,  YAO, Guomin

IPC分类号： C07D213/74 ,  C07D213/84 ,  C07D401/12 ,  C07D401/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  A61K31/444 ,  A61P25/18

CPC分类号： C07D401/04 ,  C07D213/74 ,  C07D213/84 ,  C07D401/12 ,  C07D401/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14

摘要： Pyridine and pyrimidine compounds: (I); or a pharmaceutically acceptable salt thereof, wherein m, n, R
1 , R
2 , R
3 , R
4 , R
5 , R
6 , R
7 , X
1 , X
2 , X
3 , X
4 , X
5 , X
6 , X
7 , X
8 , and Y are as defined in the specification; (II); or a pharmaceutically acceptable salt thereof, wherein ring A, m, n, y, R
2 , R
3 , R
4 , R
5 , R
6 , R
7 , R
8 , R
9 , X
1 , X
2 , and ring A are as defined in the specification; and (III); or a pharmaceutically acceptable salt thereof, wherein m, n, y, R
2 , R
3 , R
4 , R
5 , R
6 , R
7 , R
9 , X
1 , X
2 , and ring A are as defined in the specification; compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

公开(公告)号：EP1991530A1

公开(公告)日：2008-11-19

申请号：EP07751202.8

申请日：2007-02-20

申请人： Amgen Inc. ,  Memory Pharmaceuticals Corporation

发明人： ARRINGTON, Mark, P. ,  LIU, Ruiping ,  HOPPER, Allen, T. ,  CONTICELLO, Richard, D. ,  NGUYEN, Truc, M. ,  GAUSS, Carla, Maria ,  BURLI, Roland ,  HITCHCOCK, Stephen, A. ,  HU, Essa ,  KUNZ, Roxanne ,  NIXEY, Thomas ,  RUMFELT, Shannon

IPC分类号： C07D237/28 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D405/10 ,  C07D405/14 ,  C07D409/10 ,  C07D409/14 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/04 ,  C07D417/10

CPC分类号： C07D237/28 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D405/10 ,  C07D405/14 ,  C07D409/10 ,  C07D409/14 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/04 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

摘要： The present invention is directed tojcjnnoline compounds of formula (I) that are PDE 1 inhibitors, pharmaceutical compositions containing such compounds and process for preparing such compounds. This invention is also directed to methods of treating diseases treatable by inhibition of PDElO enzyme, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

摘要翻译： 本发明涉及作为PDE1抑制剂的式（I）的炔丙醇化合物，含有此类化合物的药物组合物以及制备此类化合物的方法。 本发明还涉及治疗通过抑制PDE10酶如肥胖症，非胰岛素依赖性糖尿病，精神分裂症，双相型障碍，强迫性障碍等可治疗的疾病的方法。

公开(公告)号：EP2964644B1

公开(公告)日：2018-12-26

申请号：EP14717004.7

申请日：2014-03-06

申请人： AMGEN, INC.

发明人： MINATTI, Ana Elena ,  LOW, Jonathan, D. ,  ALLEN, Jennifer, R. ,  AMEGADZIE, Albert ,  BROWN, James ,  FROHN, Michael, J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul, E. ,  LOPEZ, Patricia ,  MA, Vu Van ,  NISHIMURA, Nobuko ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert, M. ,  SHAM, Kelvin ,  SMITH, Adrian, L. ,  WHITE, Ryan ,  XUE, Qiufen

IPC分类号： C07D413/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D265/12 ,  C07D491/048 ,  A61P25/00 ,  A61K31/536

CPC分类号： C07D413/12 ,  C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

摘要： 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 A4, A5, A6, A8, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and 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 Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

公开(公告)号：EP2964644A1

公开(公告)日：2016-01-13

申请号：EP14717004.7

申请日：2014-03-06

申请人： Amgen Inc.

发明人： MINATTI, Ana Elena ,  LOW, Jonathan, D. ,  ALLEN, Jennifer, R. ,  AMEGADZIE, Albert ,  BROWN, James ,  FROHN, Michael, J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul, E. ,  LOPEZ, Patricia ,  MA, Vu Van ,  NISHIMURA, Nobuko ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert, M. ,  SHAM, Kelvin ,  SMITH, Adrian, L. ,  WHITE, Ryan ,  XUE, Qiufen

IPC分类号： C07D413/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D265/12 ,  C07D491/048 ,  A61P25/00 ,  A61K31/536

CPC分类号： C07D413/12 ,  C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

摘要： 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 A4, A5, A6, A8, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and 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 Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

摘要翻译： 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 所述化合物具有通式I：其中式I中的每个R a，R b，R 1，R 2，R 3和R 7各自独立地定义的变量A4，A5，A6，A8在本文中定义。 本发明还提供包含该化合物的药物组合物，以及由BACE的生物活性产生的化合物和组合物用于治疗与A-β斑块形成和沉积相关的病症和/或病症的用途。 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和III的化合物及其分子式实施方案，用于制备本发明化合物的中间体和方法。

公开(公告)号：EP2961749A1

公开(公告)日：2016-01-06

申请号：EP14712418.4

申请日：2014-02-27

申请人： Amgen Inc.

发明人： MINATTI, Ana Elena ,  LOW, Jonathan D. ,  ALLEN, Jennifer R. ,  CHEN, Jian ,  CHEN, Ning ,  CHENG, Yuan ,  JUDD, Ted ,  LIU, Qingyian ,  LOPEZ, Patricia ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  TAMAYO, Nuria A. ,  XUE, Qiufen ,  YANG, Bryant ,  ZHONG, Wenge

IPC分类号： C07D413/14 ,  A61K31/535 ,  A61K31/5355 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D471/04 ,  C07D265/08 ,  C07D498/04 ,  C07D513/04 ,  A61P25/00

摘要： 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 A4, A5, A6, A8, each of R1 and R2, R3 and R7 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 Formulas II and III, and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.

摘要翻译： 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 所述化合物具有通式I：其中式I中的各个R 1和R 2，R 3和R 7各自独立地定义的变量A4，A5，A6，A8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和III的化合物及其分式实施方案，可用于制备式I-III化合物的中间体和方法和方法。

公开(公告)号：EP2069020A2

公开(公告)日：2009-06-17

申请号：EP07810594.7

申请日：2007-07-18

申请人： Amgen Inc.

发明人： CHEN, Ning ,  HU, Essa ,  KUNZ, Roxanne ,  RUMFELT, Shannon ,  TASKER, Andrew

IPC分类号： A61P11/06 ,  C07D261/20 ,  A61K31/42

CPC分类号： C07D413/12 ,  C07D261/20 ,  C07D413/14

摘要： The present invention comprises a new class of compounds capable of modulating the c-kit protein kinase and, accordingly, useful for treatment of c-kit mediated diseases including, without limitation, autoimmune disease, allergies, mastocytosis, mast cell related tumors and various fibrotic diseases. The compounds have a general Formula (I) wherein R1-5, X, Y and Z are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of c-kit mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

公开(公告)号：EP3177618A1

公开(公告)日：2017-06-14

申请号：EP15766951.6

申请日：2015-08-05

申请人： Amgen Inc.

发明人： ALLEN, Jennifer R. ,  AMEGADZIE, Albert ,  BOURBEAU, Matthew P. ,  BROWN, James A. ,  CHEN, Jian J. ,  CHENG, Yuan ,  FROHN, Michael J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul E. ,  LIU, Longbin ,  LIU, Qingyian ,  LOW, Jonathan D. ,  MA, Vu Van ,  MANNING, James R. ,  MINATTI, Ana Elena ,  NGUYEN, Thomas T. ,  NISHIMURA, Nobuko ,  NORMAN, Mark H. ,  PETTUS, Liping H. ,  PICKRELL, Alexander J. ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  SIEGMUND, Aaron C. ,  STEC, Markian M. ,  WHITE, Ryan D. ,  XUE, Qiufen

IPC分类号： C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  A61K31/5415 ,  A61P25/28 ,  C07D279/08

CPC分类号： C07D417/12 ,  C07D279/08 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10

摘要： wherein variables A4, A5, A6, A8, and each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and 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 Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

摘要翻译： 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 这些化合物具有通式I：其中式I中的变量A4，A5，A6，A8以及R 1，R b，R 1，R 2，R 3和R 7各自独立地定义。 本发明还提供包含该化合物的药物组合物，以及由BACE的生物活性产生的化合物和组合物用于治疗与A-β斑块形成和沉积相关的病症和/或病症的用途。 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和III的化合物及其分子式实施方案，用于制备本发明化合物的中间体和方法。

公开(公告)号：EP2649065A1

公开(公告)日：2013-10-16

申请号：EP11802248.2

申请日：2011-12-07

申请人： Amgen Inc.

发明人： 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 ,  LANMAN, Brian, A.

IPC分类号： 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分类号： C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/04 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： 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.