公开(公告)号：WO2013086229A1

公开(公告)日：2013-06-13

申请号：PCT/US2012/068297

申请日：2012-12-06

Applicant: AMGEN INC.

Inventor： 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: 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 classification number: 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

Abstract: 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.

Abstract translation: 本发明提供式I化合物或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Nav 1.7。 （此处应插入式I）。该化合物可用于治疗通过抑制钠通道（如疼痛障碍）治疗的疾病。 还提供含有本发明化合物的药物组合物。

公开(公告)号：WO2017106871A1

公开(公告)日：2017-06-22

申请号：PCT/US2016/067617

申请日：2016-12-19

Applicant: AMGEN INC.

Inventor： WEISS, Matthew ,  MILGRAM, Benjamin C ,  MARX, Isaac E. ,  DINEEN, Thomas

IPC: C07D403/12 ,  C07D413/12 ,  A61K31/4704 ,  A61P29/00

CPC classification number: C07D403/12 ,  C07D413/12

Abstract: 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, cough, and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

Abstract translation: 本发明提供了作为电压门控钠通道抑制剂，特别是Nav1.7的式（I）化合物及其药学上可接受的盐。 该化合物可用于治疗与钠通道活性有关的疾病，例如疼痛疾病，咳嗽和瘙痒。 还提供了含有本发明化合物的药物组合物。

公开(公告)号：WO2013122897A1

公开(公告)日：2013-08-22

申请号：PCT/US2013/025668

申请日：2013-02-12

Applicant: AMGEN INC.

Inventor： BOEZIO, Christiane ,  BOEZIO, Alessandro ,  BREGMAN, Howard ,  CHAKKA, Nagasree ,  COATS, James R. ,  COPELAND, Katrina W. ,  DIMAURO, Erin F. ,  DINEEN, Thomas ,  GAO, Hua ,  LA, Daniel ,  MARX, Isaac E. ,  NGUYEN, Hanh Nho ,  PETERSON, Emily Anne ,  WEISS, Matthew

IPC: C07D413/14 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  A61K31/538 ,  A61P29/00

CPC classification number: C07D417/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04

Abstract: 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 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.

Abstract translation: 本发明提供式I化合物或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Nav 1.7。 该化合物可用于治疗通过抑制钠通道（例如疼痛障碍）可治疗的疾病。 还提供含有本发明化合物的药物组合物。

公开(公告)号：WO2013025883A1

公开(公告)日：2013-02-21

申请号：PCT/US2012/051100

申请日：2012-08-16

Applicant: DINEEN, Thomas ,  MARX, Isaac, E. ,  NGUYEN, Hanh, Nho ,  WEISS, Matthew ,  AMGEN INC.

Inventor： DINEEN, Thomas ,  MARX, Isaac, E. ,  NGUYEN, Hanh, Nho ,  WEISS, Matthew

IPC: C07D403/14 ,  C07D417/12 ,  C07D417/14 ,  A61K31/404 ,  A61K31/4184 ,  A61P29/00

CPC classification number: C07D471/04 ,  C07D403/14 ,  C07D417/12 ,  C07D417/14

Abstract: The present invention provides compounds of Formula I or II, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of channels such as pain disorders. Also provided are pharmaceutical compositions containing compounds of the present invention.

Abstract translation: 本发明提供式I或II的化合物或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Nav 1.7。 该化合物可用于治疗通过抑制诸如疼痛障碍的通道可治疗的疾病。 还提供含有本发明化合物的药物组合物。

公开(公告)号：WO2012071279A1

公开(公告)日：2012-05-31

申请号：PCT/US2011/061473

申请日：2011-11-18

Applicant: AMGEN INC. ,  MINATTI, Ana Elena ,  EPSTEIN, Oleg ,  WHITE, Ryan ,  WEISS, Matthew ,  ZHONG, Wenge ,  LOW, Jonathan

Inventor： MINATTI, Ana Elena ,  EPSTEIN, Oleg ,  WHITE, Ryan ,  WEISS, Matthew ,  ZHONG, Wenge ,  LOW, Jonathan

IPC: C07D491/20 ,  A61K31/527 ,  A61P25/28

CPC classification number: C07D491/107 ,  C07D491/20

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 1 , A 3 , A 4 , A 5 , A 6 , A 8 , L, R 2 , R 7 , R 9 , W and Y of Formula (I) 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 plaque formation and deposition, resulting from the 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), sub-Formula embodiments of Formulas (I), (II) and (III), intermediates and processes and methods useful for the preparation of compounds of Formulae (I-III).

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A1，A3，A4，A5，A6，A8，L，R2，R7，R9，W和Y如本文所定义。 本发明还提供包含该化合物的药物组合物，以及用于治疗由于BACE的活性而导致的与斑块形成和沉积有关的疾病和/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，式（I），（II）和（III）的分式实施方案，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：WO2007061670A1

公开(公告)日：2007-05-31

申请号：PCT/US2006/044058

申请日：2006-11-13

Applicant: AMGEN INC. ,  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

Inventor： 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: C07D405/12 ,  C07D413/12 ,  A61K31/44 ,  A61P25/28

CPC classification number: C07D405/12 ,  C07D311/68 ,  C07D413/12 ,  C07D491/052

Abstract: 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, R 3 , R 4 , R 5 , 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.

Abstract translation: 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A，B，W，R 3，R 4，R 5，i和j在本文中定义。 本发明还包括药物组合物，其包括一种或多种式（I）化合物，这些化合物的使用方法，包括治疗AD和相关疾病，通过施用式（I）化合物或其组合物，包括它们， 到一个主题。 本发明还包括式（II）和（III）的其它实施方案，可用于制备本发明化合物的中间体和方法。

公开(公告)号：WO2017106872A1

公开(公告)日：2017-06-22

申请号：PCT/US2016/067622

申请日：2016-12-19

Applicant: AMGEN INC

Inventor： WEISS, Matthew ,  DINEEN, Thomas ,  VAIDA, Karina R.

IPC: C07D403/12 ,  C07D413/14 ,  A61K31/4704 ,  C07D215/36 ,  C07D413/12 ,  C07D241/44 ,  C07D417/12

CPC classification number: C07D413/14 ,  A61K31/4704 ,  C07D215/36 ,  C07D241/44 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12

Abstract: 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, cough, and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

Abstract translation: 本发明提供了作为电压门控钠通道抑制剂，特别是Nav1.7的式I化合物及其药学上可接受的盐。 该化合物可用于治疗与钠通道活性有关的疾病，例如疼痛疾病，咳嗽和瘙痒。 还提供了含有本发明化合物的药物组合物。

公开(公告)号：WO2016141035A1

公开(公告)日：2016-09-09

申请号：PCT/US2016/020403

申请日：2016-03-02

Applicant: AMGEN INC.

Inventor： WEISS, Matthew ,  MILGRAM, Benjamin C. ,  DINEEN, Thomas ,  STELLWAGEN, John ,  GUZMAN-PEREZ, Angel ,  BOEZIO, Alessandro ,  MARX, Isaac E.

IPC: C07D471/04 ,  A61K31/437 ,  A61P29/00

CPC classification number: C07D471/04

Abstract: The present invention provides compounds of Formula (I), wherein: Formula (II) as defined in the specification, an enantiomer, diastereomer, atropisomer thereof, or a mixture thereof, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders, cough, or itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

Abstract translation: 本发明提供式（I）化合物，其中：如本说明书中定义的式（II），其对映异构体，非对映异构体，阻转异构体或其混合物或其药学上可接受的盐，其为电压门控钠 渠道，特别是Nav 1.7。 该化合物可用于治疗通过抑制钠通道（例如疼痛障碍，咳嗽或瘙痒）可治疗的疾病。 还提供含有本发明化合物的药物组合物。

公开(公告)号：WO2011115928A1

公开(公告)日：2011-09-22

申请号：PCT/US2011/028401

申请日：2011-03-14

Applicant: AMGEN INC. ,  CHEN, Jian, J. ,  ZHONG, Wenge ,  YANG, Bryant ,  QIAN, Wenyuan ,  LOPEZ, Patricia ,  WHITE, Ryan ,  WEISS, Matthew ,  JUDD, Ted ,  POWERS, Timothy ,  CHENG, Yuan ,  DINEEN, Thomas ,  EPSTEIN, Oleg ,  LOW, Jonathan ,  MARX, Isaac ,  MINATTI, Ana Elena ,  PARAS, Nick, A. ,  POTASHMAN, Michele

Inventor： CHEN, Jian, J. ,  ZHONG, Wenge ,  YANG, Bryant ,  QIAN, Wenyuan ,  LOPEZ, Patricia ,  WHITE, Ryan ,  WEISS, Matthew ,  JUDD, Ted ,  POWERS, Timothy ,  CHENG, Yuan ,  DINEEN, Thomas ,  EPSTEIN, Oleg ,  LOW, Jonathan ,  MARX, Isaac ,  MINATTI, Ana Elena ,  PARAS, Nick, A. ,  POTASHMAN, Michele

IPC: C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20 ,  A61K31/537 ,  A61K31/5386 ,  A61K31/547 ,  A61P25/28

CPC classification number: C07D513/10 ,  C07D498/10 ,  C07D498/20 ,  C07D513/20

Abstract: 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 , R 2 , R 7 , 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).

Abstract translation: 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，Y和Z在本文中定义。 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。

公开(公告)号：WO2007062007A1

公开(公告)日：2007-05-31

申请号：PCT/US2006/045004

申请日：2006-11-20

Applicant: AMGEN INC. ,  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

Inventor： 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: C07D405/12 ,  C07D413/12 ,  A61K31/44 ,  A61P25/28

CPC classification number: C07D405/12 ,  C07D413/12

Abstract: 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, R 3 , R 4 , R 5 , 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.

Abstract translation: 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A，B，R 3，R 4，R 5，i和j分别为 本文定义。 本发明还包括药物组合物，其包括一种或多种式I化合物，这些化合物的使用方法，包括治疗AD和相关疾病，通过给受试者施用式I化合物或包含它们的组合物。 本发明还包括式II和III的其它实施方案，可用于制备本发明化合物的中间体和方法。