公开(公告)号：WO2009051718A2

公开(公告)日：2009-04-23

申请号：PCT/US2008/011755

申请日：2008-10-15

Applicant: AMGEN INC. ,  COULTER, Thomas S. ,  FOTSCH, Christopher H. ,  GHIRON, Chiara ,  HARRINGTON, Paul E. ,  KELLY, Michael G. ,  MILLER, Philip ,  RISHTON, Gilbert M. ,  ST. JEAN, David J., Jr. ,  SEMIN, David J.

Inventor： COULTER, Thomas S. ,  FOTSCH, Christopher H. ,  GHIRON, Chiara ,  HARRINGTON, Paul E. ,  KELLY, Michael G. ,  MILLER, Philip ,  RISHTON, Gilbert M. ,  ST. JEAN, David J., Jr. ,  SEMIN, David J.

IPC: C07D207/48 ,  C07D231/12 ,  C07D231/16 ,  C07D231/22 ,  C07D233/64 ,  C07D261/08 ,  C07D271/06 ,  C07D277/28 ,  C07D401/04 ,  C07D207/335 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/40 ,  A61P7/00

CPC classification number: C07D233/64 ,  C07D207/335 ,  C07D207/48 ,  C07D231/12 ,  C07D231/16 ,  C07D231/22 ,  C07D261/08 ,  C07D271/06 ,  C07D277/28 ,  C07D401/04

Abstract: The present invention relates generally to novel calcimimetic compounds and pharmaceutical compositions comprising them. The invention also relates to methods of treating of diseases or disorders related to the function of the calcium sensing receptor using the compounds represented in Formula I.

Abstract translation: 本发明一般涉及新型的拟钙化合物和包含它们的药物组合物。 本发明还涉及使用式I表示的化合物治疗与钙感受受体的功能相关的疾病或病症的方法。

公开(公告)号：WO2018112083A1

公开(公告)日：2018-06-21

申请号：PCT/US2017/066179

申请日：2017-12-13

Applicant: AMGEN INC.

Inventor： BOURBEAU, Matthew P. ,  HARRINGTON, Paul E. ,  LIU, Qingyian

IPC: C07D417/10 ,  A61P25/00 ,  A61P25/28 ,  A61K31/541

Abstract: The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: (see Formula I structure) wherein variables R 1 , R 1' , R 2 , R 2' , R 3 , R 4 , R 5 , R 6 , R 7 , and b of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ 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, and other central nervous system conditions.

公开(公告)号：WO2011143129A1

公开(公告)日：2011-11-17

申请号：PCT/US2011/035780

申请日：2011-05-09

Applicant: AMGEN INC. ,  ALLEN, Jennifer R. ,  ANDREWS, Kristin L. ,  FROHN, Michael J. ,  HARRINGTON, Paul E. ,  PICKRELL, Alexander J. ,  RZASA, Robert M.

Inventor： ALLEN, Jennifer R. ,  ANDREWS, Kristin L. ,  FROHN, Michael J. ,  HARRINGTON, Paul E. ,  PICKRELL, Alexander J. ,  RZASA, Robert M.

IPC: C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D471/14 ,  A61P3/00 ,  A61P25/00 ,  A61K31/444 ,  A61K31/467 ,  A61K31/506 ,  A61K31/4709 ,  A61K31/4375

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

Abstract: Aryl- and heteroaryl-nitrogen heterocyclic compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDEIO, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 芳基和杂芳基氮杂环化合物和含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDEIO可治疗的疾病或疾病的方法，例如肥胖症，非胰岛素依赖性糖尿病，精神分裂症，亨廷顿舞蹈病，双相情感障碍，强迫症等。

公开(公告)号：WO2018183418A1

公开(公告)日：2018-10-04

申请号：PCT/US2018/024723

申请日：2018-03-28

Applicant: AMGEN INC.

Inventor： HARRINGTON, Paul E. ,  ASHTON, Kate ,  BROWN, Sean P. ,  KALLER, Matthew R. ,  KOHN, Todd J. ,  LANMAN, Brian Alan ,  LI, Kexue ,  LI, Yunxiao ,  LOW, Jonathan D. ,  MINATTI, Ana Elena ,  PICKRELL, Alexander J. ,  STEC, Markian M. ,  TAYGERLY, Joshua

IPC: C07D498/08 ,  A61K31/553 ,  A61P35/00 ,  A61P35/02

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (I), or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

公开(公告)号：WO2018112081A1

公开(公告)日：2018-06-21

申请号：PCT/US2017/066177

申请日：2017-12-13

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer R. ,  BOURBEAU, Matthew P. ,  CHEN, Ning ,  FROHN, Michael J. ,  HARRINGTON, Paul E. ,  LIU, Qingyian ,  REEVES, Corey

IPC: C07D413/10 ,  C07D265/08 ,  C07D265/12 ,  C07D265/30 ,  A61K31/5355 ,  A61K31/5377 ,  A61P25/28

Abstract: The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: (insert Formula I structure) wherein variables W, X, Y, R 2 , R 2' , R 3 , R 4 , R 5 , R 6 , and R 7 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to beta amyloid (Aβ) 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, and other central nervous system conditions.

公开(公告)号：WO2016022724A1

公开(公告)日：2016-02-11

申请号：PCT/US2015/043868

申请日：2015-08-05

Applicant: AMGEN INC.

Inventor： 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 ,  MINATTI, Ana Elena ,  NGUYEN, Thomas T. ,  NISHMURA, 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 ,  XUE, Qiufen

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

CPC classification number: C07D417/12 ,  C07D279/08 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10

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 4 , A 5 , A 6 , A 8 , and each of R a , R b , R 1 , R 2 , R 3 and R 7 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 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers 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.

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）的各个变量A4，A5，A6，A8和R a，R b，R 1，R 2，R 3和R 7各自独立地在本文中定义。 本发明还提供了包含该化合物的药物组合物，以及该化合物和组合物用于治疗由BACE生物活性导致的A-β斑块形成和15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：WO2019046150A1

公开(公告)日：2019-03-07

申请号：PCT/US2018/048058

申请日：2018-08-27

Applicant: AMGEN INC.

Inventor： BROWN, Sean P. ,  HARRINGTON, Paul E. ,  LANMAN, Brian Alan ,  LI, Kexue ,  LI, Yunxiao ,  LOW, Jonathan D. ,  MA, Vu Van ,  MINATTI, Ana Elena

IPC: C07D513/08 ,  A61K31/554 ,  A61P35/00

CPC classification number: C07D513/08

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

公开(公告)号：WO2018112086A1

公开(公告)日：2018-06-21

申请号：PCT/US2017/066184

申请日：2017-12-13

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer R. ,  AMEGADZIE, Albert ,  BOURBEAU, Matthew P. ,  CHEN, Jian J. ,  FROHN, Michael J. ,  HARRINGTON, Paul E. ,  LOW, Jonathan D. ,  MA, Vu V. ,  NGUYEN, Thomas T. ,  PICKRELL, Alexander J. ,  REEVES, Corey

IPC: C07D417/10 ,  C07D417/14 ,  C07D279/08 ,  A61P25/28 ,  A61K31/5415

Abstract: The present disclosure 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, R 1 , R 2 , R 2' , R 3 , R 4 , and R 5 of Formula (I) are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to Aβ 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, and other central nervous system conditions.

公开(公告)号：WO2014059185A1

公开(公告)日：2014-04-17

申请号：PCT/US2013/064400

申请日：2013-10-10

Applicant: AMGEN INC.

Inventor： LEWIS, Richard T. ,  CHOQUETTE, Deborah ,  EPSTEIN, Oleg ,  GUZMAN-PEREZ, Angel ,  HUA, Zihao ,  HUMAN, Jason Brooks ,  JUDD, Ted ,  LIU, Qingyian ,  LOPEZ, Patricia ,  MINATTI, Ana Elena ,  OLIVIERI, Philip R. ,  ROMERO, Karina ,  SCHENKEL, Laurie ,  STELLWAGEN, John ,  WHITE, Ryan ,  ZHENG, Xiao Mei ,  ALLEN, Jennifer R. ,  CHENG, Yuan ,  HARRINGTON, Paul E. ,  HUNGATE, Randall W. ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  XUE, Qiufen ,  ZHONG, Wenge

IPC: C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  C07D279/12 ,  C07D279/14 ,  C07D513/04 ,  C07D513/10 ,  C07D519/00 ,  A61P25/18 ,  A61P25/28 ,  A61K31/54 ,  A61K31/541 ,  A61K31/547

CPC classification number: C07D279/12 ,  C07D213/79 ,  C07D239/74 ,  C07D241/44 ,  C07D279/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  C07D513/10 ,  C07D519/00

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 4 , A 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 and n 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 Formula II and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.

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A4，A5，A6，A8，R1，R2，R3，R7和n独立地在本文中定义。 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化合物及其次级实施方案，可用于制备式I-II化合物的中间体和方法和方法。