公开(公告)号：EP1954693A1

公开(公告)日：2008-08-13

申请号：EP06838143.3

申请日：2006-11-20

申请人： Amgen Inc.

发明人： 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分类号： C07D405/12 ,  C07D413/12 ,  A61K31/44 ,  A61P25/28

CPC分类号： C07D405/12 ,  C07D413/12

摘要： 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, R3, R4, R5, 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.

摘要翻译： 本发明包括用于调节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）的一类新化合物。 在一个实施方案中，所述化合物具有通式I，其中A，B，R 3，R 4，R 5，i和j如本文所定义。 本发明还包括药物组合物，其包含一种或多种式I化合物，用于这些化合物的方法，包括治疗AD和相关疾病，通过将式I化合物或包含它们的组合物施用于受试者。 本发明还包括式II和III的进一步实施方案，用于制备本发明化合物的中间体和方法。

公开(公告)号：EP2167471B1

公开(公告)日：2013-10-16

申请号：EP08754710.5

申请日：2008-05-23

申请人： Amgen Inc.

发明人： ZHONG, Wenge ,  HITCHCOCK, Stephen ,  PATEL, Vinod F. ,  CROGHAN, Michael ,  DINEEN, Thomas ,  HORNE, Daniel ,  KALLER, Matthew ,  KREIMAN, Charles ,  LOPEZ, Patricia ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  PENNINGTON, Lewis ,  XUE, Qiufen ,  YANG, Bryant

IPC分类号： C07D221/06 ,  C07D311/96 ,  C07D471/10 ,  C07D491/10 ,  C07D493/10 ,  C07D495/10 ,  A61P25/28 ,  A61K31/438

CPC分类号： C07D491/107 ,  C07D221/06 ,  C07D311/96 ,  C07D471/10 ,  C07D491/10 ,  C07D493/10 ,  C07D495/10

公开(公告)号：EP1976836A2

公开(公告)日：2008-10-08

申请号：EP06848110.0

申请日：2006-12-22

申请人： Amgen Inc.

发明人： DE MORIN, Frenel, F. ,  CHEN, Jian J. ,  DOHERTY, Elizabeth M. ,  HITCHCOCK, Stephen ,  HUANG, Qi ,  KIM, Joseph, L. ,  LIU, Gang ,  NIXEY, Thomas ,  PARAS, Nick, A. ,  PETKUS, Jeffrey ,  RETZ, Daniel, M. ,  SMITH, Adrian, L. ,  TASKER, Andrew ,  ZHU, Jiawang

IPC分类号： C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D401/14

CPC分类号： C07D401/14 ,  C07D239/84 ,  C07D239/95 ,  C07D401/04 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04

摘要： The present invention comprises a new class of compounds capable of modulating Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have Formula (I) wherein R1 is Formula (II), (III) or (IV) and A1, A2, A3, A4, X, Z, Z', R1, R2, R3, R4, R5 and R6 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

公开(公告)号：EP1971598A1

公开(公告)日：2008-09-24

申请号：EP06837478.4

申请日：2006-11-13

申请人： Amgen Inc.

发明人： 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分类号： C07D405/12 ,  C07D413/12 ,  A61K31/44 ,  A61P25/28

CPC分类号： C07D405/12 ,  C07D311/68 ,  C07D413/12 ,  C07D491/052

摘要： 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, R3, R4, R5, 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.

公开(公告)号：EP1963312A1

公开(公告)日：2008-09-03

申请号：EP06838016.1

申请日：2006-11-17

申请人： Amgen Inc.

发明人： XUE, Qiufen ,  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 ,  YANG, Bryant ,  ZHONG, Wenge

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

CPC分类号： C07D405/12 ,  C07D413/12

摘要： 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 R1, W, B, R3, R4, R5, 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.

摘要翻译： 本发明包括用于调节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）的一类新化合物。 在一个实施方案中，所述化合物具有通式（I）其中R 1，W，B，R 3，R 4，R 5，i和j如本文所定义。 本发明还包括药物组合物，其包含一种或多种式（I）化合物，用于这些化合物的方法，包括治疗AD和相关疾病，通过施用式（I）化合物或包含它们的组合物， 到一个主题。 本发明还包括式（II）和（III）的其他实施方案，可用于制备本发明化合物的中间体和方法。

公开(公告)号：EP2504330A1

公开(公告)日：2012-10-03

申请号：EP10787618.7

申请日：2010-11-19

申请人： Amgen Inc.

发明人： PARAS, Nick A, ,  CHENG, Yuan ,  POWERS, Timothy ,  BROWN, James ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  XUE, Qiufen ,  YANG, Bryant

IPC分类号： C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  A61K31/4709 ,  A61P25/28

CPC分类号： C07D401/06 ,  C07D401/12 ,  C07D401/14

摘要： 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 ring A, B
1 , B
2 , B
3 , L, R
1 , R
4 , ring Z, m and p of Formula I 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, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

公开(公告)号：EP2167471A1

公开(公告)日：2010-03-31

申请号：EP08754710.5

申请日：2008-05-23

申请人： Amgen Inc.

发明人： ZHONG, Wenge ,  HITCHCOCK, Stephen ,  PATEL, Vinod F. ,  CROGHAN, Michael ,  DINEEN, Thomas ,  HORNE, Daniel ,  KALLER, Matthew ,  KREIMAN, Charles ,  LOPEZ, Patricia ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  PENNINGTON, Lewis ,  XUE, Qiufen ,  YANG, Bryant

IPC分类号： C07D221/06 ,  C07D311/96 ,  C07D471/10 ,  C07D491/10 ,  C07D493/10 ,  C07D495/10 ,  A61P25/28 ,  A61K31/438

CPC分类号： C07D491/107 ,  C07D221/06 ,  C07D311/96 ,  C07D471/10 ,  C07D491/10 ,  C07D493/10 ,  C07D495/10

摘要： 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 R1a, R1b, R1c, B, W, R3, R4 and R5 are defined herein. In another embodiment, the invention provides compounds of general Formula II wherein A1, A2, A3, A4, R1a, R1b, R1c, R2, R4, R5, W, 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.

公开(公告)号：EP2041088A1

公开(公告)日：2009-04-01

申请号：EP07796466.6

申请日：2007-06-26

申请人： AMGEN INC.

发明人： HITCHCOCK, Stephen ,  AMAGADZIE, Albert ,  QIAN, Wenyuan ,  XIA, Xiaoyang ,  HARRIED, Scott S.

IPC分类号： C07D213/36 ,  C07D243/08 ,  C07D295/14 ,  C07D333/20 ,  A61P25/18 ,  A61K31/495 ,  C07D241/04

CPC分类号： C07D241/04 ,  A61K31/495 ,  A61K31/551 ,  A61K33/00 ,  C07D213/36 ,  C07D241/08 ,  C07D243/08 ,  C07D295/15 ,  C07D333/20

摘要： The present invention provides compounds of formula (I) that are glycine transporter 1 (hereinafter referred to as GlyT-1) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of GlyT1 such as cognitive disorders associated with Schizophrenia, ADHD (attention deficit hyperactivity disorder), MCI (mild cognitive impairment), and the like. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.