公开(公告)号：EP1963312B1

公开(公告)日：2014-07-02

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

公开(公告)号：EP2328903B1

公开(公告)日：2014-03-05

申请号：EP09737222.1

申请日：2009-09-11

申请人： Amgen Inc.

发明人： WHITE, Ryan ,  AMEGADZIE, Albert ,  BRYAN, Marian C. ,  CHEN, Jian J. ,  CHENG, Alan C. ,  DINEEN, Thomas ,  EPSTEIN, Oleg ,  GORE, Vijay Keshav ,  HUA, Zihao ,  HUMAN, Jason B. ,  HUANG, Hongbing ,  KREIMAN, Charles ,  LA, Daniel ,  LIU, Qingyian ,  MA, Vu Van ,  MARX, Isaac ,  PATEL, Vinod F. ,  QIAN, Wenyuan ,  WEISS, Matthew ,  YUAN, Chester C.

IPC分类号： C07D498/10 ,  C07D513/10 ,  A61K31/424 ,  A61K31/429 ,  A61P25/28

CPC分类号： C07D498/10 ,  C07D513/10

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：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：EP2788332A1

公开(公告)日：2014-10-15

申请号：EP12809010.7

申请日：2012-12-06

申请人： AMGEN, INC.

发明人： 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分类号： 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分类号： 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

摘要： 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.

公开(公告)号：EP2328903A1

公开(公告)日：2011-06-08

申请号：EP09737222.1

申请日：2009-09-11

申请人： Amgen Inc.

发明人： WHITE, Ryan ,  AMEGADZIE, Albert ,  BRYAN, Marian C. ,  CHEN, Jian J. ,  CHENG, Alan C. ,  DINEEN, Thomas ,  EPSTEIN, Oleg ,  GORE, Vijay Keshav ,  HUA, Zihao ,  HUMAN, Jason B. ,  HUANG, Hongbing ,  KREIMAN, Charles ,  LA, Daniel ,  LIU, Qingyian ,  MA, Vu Van ,  MARX, Isaac ,  PATEL, Vinod F. ,  QIAN, Wenyuan ,  WEISS, Matthew ,  YUAN, Chester C.

IPC分类号： C07D498/10 ,  C07D513/10 ,  A61K31/424 ,  A61K31/429 ,  A61P25/28

CPC分类号： C07D498/10 ,  C07D513/10

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 A
1 , A
2 , A
3 , A
4 , A
5 , A
6 , T
1 , T
2 , W, X, Y and Z 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, 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：EP3008057A1

公开(公告)日：2016-04-20

申请号：EP14738676.7

申请日：2014-06-12

申请人： Amgen Inc.

发明人： WEISS, Matthew ,  BOEZIO, Alessandro ,  BOEZIO, Christiane ,  BUTLER, John R. ,  CHU-MOYER, Margaret Yuhua ,  DIMAURO, Erin F. ,  DINEEN, Thomas ,  GRACEFFA, Russell ,  GUZMAN-PEREZ, Angel ,  HUANG, Hongbin ,  KREIMAN, Charles ,  LA, Daniel ,  MARX, Isaac E. ,  MILGRIM, Benjamin Charles ,  NGUYEN, Hanh Nho ,  PETERSON, Emily ,  ROMERO, Karina ,  SPARLING, Brian

IPC分类号： C07D403/12 ,  C07D413/14 ,  C07D215/36 ,  C07D413/12 ,  C07D241/44 ,  C07D417/12 ,  A61K31/4704 ,  A61P29/00

CPC分类号： C07D417/14 ,  C07C53/18 ,  C07D215/227 ,  C07D215/36 ,  C07D241/44 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

摘要： The present invention provides compounds of Formula I, and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

摘要翻译： 本发明提供式I化合物及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Nav1.7。 该化合物可用于治疗与钠通道活性相关的疾病，例如疼痛障碍和瘙痒。 还提供含有本发明化合物的药物组合物。

公开(公告)号：EP2547685A1

公开(公告)日：2013-01-23

申请号：EP11710372.1

申请日：2011-03-14

申请人： Amgen Inc.

发明人： CHENG, Yuan ,  WHITE, Ryan ,  AMEGADZIE, Albert ,  BROWN, James ,  CHENG, Alan, C. ,  DIMAURO, Erin, F. ,  DINEEN, Thomas ,  GORE, Vijay Keshav ,  HUMAN, Jason, Brooks ,  JUDD, Ted ,  KREIMAN, Charles ,  LIU, Qingyian ,  LOPEZ, Patricia ,  MA, Vu, Van ,  MARX, Isaac ,  MINATTI, Ana, Elena ,  NGUYEN, Hanh, Nho ,  PARAS, Nick, A. ,  PATEL, Vinod, F. ,  QIAN, Wenyuan ,  WEISS, Matthew ,  XUE, Qiufen ,  ZHENG, Xiao Mei ,  ZHONG, Wenge ,  EPSTEIN, Oleg

IPC分类号： C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  A61K31/424 ,  A61K31/429 ,  A61P25/28

CPC分类号： C07D491/10 ,  A61K31/42 ,  A61K31/422 ,  A61K31/4439 ,  A61K31/506 ,  A61K31/5377 ,  C07D221/20 ,  C07D235/02 ,  C07D263/08 ,  C07D295/135 ,  C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C09B11/28

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 other related conditions. In one embodiment, the compounds have a general Formula (I) wherein A
1 , A
2 , A
3 , A
4 , A
5 , A
6 , R
2 , R
7 , X and Y 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, 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.

摘要翻译： 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））和其它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，其中式I的A1，A2，A3，A4，A5，A6，R2，R7，X和Y定义如下。 本发明还包括这些化合物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病症和病症的用途。 这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。