公开(公告)号：WO2013188724A1

公开(公告)日：2013-12-19

申请号：PCT/US2013/045768

申请日：2013-06-14

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer R. ,  CHEN, Jian J. ,  FROHN, Michael J. ,  KALLER, Matthew Richard ,  LIU, Qingyian ,  NGUYEN, Thomas T. ,  PICKRELL, Alexander J. ,  QIAN, Wenyuan ,  RZASA, Robert M. ,  ZHONG, Wenge

IPC: C07D401/14 ,  C07D403/14 ,  A61K31/497 ,  A61P25/00

CPC classification number: C07D471/04 ,  A61K31/497 ,  A61K31/517 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14

Abstract: Azetidine and piperidine compounds of formula (I) as defined in the specification, compositions containing them, and processes for preparing such compounds and intermediates thereof. Provided herein also are methods of treating cognitive disorders or diseases treatable by inhibition of PDE10, such as Huntington's Disease, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 说明书中定义的式（I）的氮杂环丁烷和哌啶化合物，含有它们的组合物，以及制备这些化合物的方法及其中间体。 本文还提供治疗认知障碍或通过抑制PDE10可治疗的疾病的方法，例如亨廷顿病，精神分裂症，双相障碍，强迫症等。

公开(公告)号：WO2007070359A2

公开(公告)日：2007-06-21

申请号：PCT/US2006/046785

申请日：2006-12-08

Applicant: AMGEN INC. ,  ALLEN, Jennifer R. ,  TEGLEY, Christopher M. ,  BISWAS, Kaustav ,  BURLI, Roland ,  MULLER, Kristine M. ,  FROHN, Michael J. ,  GOLDEN, Jennifer E. ,  MERCEDE, Stephanie J. ,  NEIRA, Susana C. ,  PETERKIN, Tanya A. N. ,  HUNGATE, Randall W. ,  KURZEJA, Robert ,  YU, Violeta ,  DAO, Jennifer

Inventor： ALLEN, Jennifer R. ,  TEGLEY, Christopher M. ,  BISWAS, Kaustav ,  BURLI, Roland ,  MULLER, Kristine M. ,  FROHN, Michael J. ,  GOLDEN, Jennifer E. ,  MERCEDE, Stephanie J. ,  NEIRA, Susana C. ,  PETERKIN, Tanya A. N. ,  HUNGATE, Randall W. ,  KURZEJA, Robert ,  YU, Violeta ,  DAO, Jennifer

CPC classification number: C07D215/22 ,  C07D215/56 ,  C07D401/04 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  G01N33/542

Abstract: This invention relates to new quinolone based compounds that exhibit prolyl hydroxylase inhibitory activity. This invention also relates to methods of increasing HIF levels or activity in a subject or treating a condition associated with HIF levels or activity in a subject by administering to the subject at least one quinolone based compound. This invention further involves assays for the detection of a hydroxyproline residue in a HIF molecule.

Abstract translation: 本发明涉及显示脯氨酰羟化酶抑制活性的新型喹诺酮类化合物。 本发明还涉及通过向受试者施用至少一种基于喹诺酮的化合物来增加受试者中HIF水平或活性或治疗与受试者中HIF水平或活性相关的病症的方法。 本发明还涉及用于检测HIF分子中的羟脯氨酸残基的测定法。

公开(公告)号：WO2021108404A1

公开(公告)日：2021-06-03

申请号：PCT/US2020/062011

申请日：2020-11-24

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer R. ,  AMEGADZIE, Albert ,  BOURBEAU, Matthew P. ,  CHEN, Ning ,  GOODMAN, Clifford ,  LATTANZI, Giulia ,  LINGARD, Iain ,  LIU, Qingyian ,  LOW, Jonathan D. ,  MA, Vu Van ,  MINATTI, Ana E. ,  POZZAN, Alfonso ,  REEVES, Corey ,  SIEGMUND, Aaron C. ,  TASSINI, Sabrina ,  TONELLI, Federica ,  WALTON, Mary

IPC: C07D471/04 ,  A61K31/517 ,  A61K31/519 ,  C07D487/04 ,  C07D498/04 ,  A61P3/00 ,  A61P9/00

Abstract: The present disclosure provides compounds useful for the inhibition of Delta-5 Desaturase ("D5D"). The compounds have a general Formula (I): wherein the variables of Formula (I) are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a metabolic or cardiovascular disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

公开(公告)号：WO2014120658A1

公开(公告)日：2014-08-07

申请号：PCT/US2014/013340

申请日：2014-01-28

Applicant: AMGEN INC.

Inventor： WHITE, Ryan ,  ALLEN, Jennifer R. ,  EPSTEIN, Oleg ,  HONG, Fang-Tsao ,  HUA, Zihao ,  HUMAN, Jason Brooks ,  LOPEZ, Patricia ,  OLIVIERI, Philip R. ,  ROMERO, Karina ,  SCHENKEL, Laurie ,  STELLWAGEN, John ,  TAMAYO, Nuria A. ,  ZHENG, Xiao Mei

IPC: C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  C07D513/10 ,  C07D513/14 ,  C07D513/20 ,  C07D519/00 ,  A61K31/5415 ,  A61K31/542 ,  A61K31/547 ,  A61K31/55 ,  A61P25/00 ,  A61P25/28

CPC classification number: C07D513/04 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/10 ,  C07D513/14 ,  C07D513/20 ,  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 5 , A 6 , A 8 , R 1 , R 2 , R 3 , R 7 , X, Y, n and o 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, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.

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A5，A6，A8，R1，R2，R3，R7，X，Y，n和o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。 本发明进一步提供式II化合物及其分式实施方案，式III化合物，可用于制备式I-III化合物及其分式的中间体和方法和方法。

公开(公告)号：WO2010057126A1

公开(公告)日：2010-05-20

申请号：PCT/US2009/064643

申请日：2009-11-16

Applicant: AMGEN INC. ,  ALLEN, Jennifer R. ,  BISWAS, Kaustav ,  CHAVEZ, Frank, Jr. ,  CHEN, Ning ,  DEMORIN, Frenel Fils ,  FALSEY, James R. ,  FROHN, Mike ,  HARRINGTON, Paul ,  HORNE, Dan ,  HU, Essa ,  KALLER, Matthew R. ,  KUNZ, Roxanne ,  MONENSCHEIN, Holger ,  NGUYEN, Tom ,  PICKRELL, Alex ,  REICHELT, Andreas ,  RUMFELT, Shannon ,  RZASA, Rob ,  SHAM, Kelvin ,  YAO, Guomin

Inventor： ALLEN, Jennifer R. ,  BISWAS, Kaustav ,  CHAVEZ, Frank, Jr. ,  CHEN, Ning ,  DEMORIN, Frenel Fils ,  FALSEY, James R. ,  FROHN, Mike ,  HARRINGTON, Paul ,  HORNE, Dan ,  HU, Essa ,  KALLER, Matthew R. ,  KUNZ, Roxanne ,  MONENSCHEIN, Holger ,  NGUYEN, Tom ,  PICKRELL, Alex ,  REICHELT, Andreas ,  RUMFELT, Shannon ,  RZASA, Rob ,  SHAM, Kelvin ,  YAO, Guomin

IPC: C07D401/12 ,  C07D401/14 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  A61K31/4184 ,  A61P25/18 ,  A61P3/00

CPC classification number: C07D413/14 ,  C07D401/12 ,  C07D401/14 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00

Abstract: Pyridine and pyrimidine 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 PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 吡啶和嘧啶化合物，以及含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症，非胰岛素依赖型糖尿病，精神分裂症，双相情感障碍，强迫症等。

公开(公告)号：WO2008137060A1

公开(公告)日：2008-11-13

申请号：PCT/US2008/005664

申请日：2008-04-29

Applicant: AMGEN INC. ,  ALLEN, Jennifer R. ,  BURLI, Roland ,  FROHN, Michael J. ,  HUNGATE, Randall W. ,  NEIRA, Susana C. ,  REED, Anthony B.

Inventor： ALLEN, Jennifer R. ,  BURLI, Roland ,  FROHN, Michael J. ,  HUNGATE, Randall W. ,  NEIRA, Susana C. ,  REED, Anthony B.

IPC: A61K31/4365 ,  A61K31/437 ,  A61P7/06 ,  A61P9/10 ,  A61P9/12 ,  A61P3/10 ,  A61P17/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D495/04 ,  C07D513/04

CPC classification number: A61K31/4365 ,  A61K31/437 ,  C07D495/04 ,  C07D513/04

Abstract: Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have the following structure:(I) where the definitions of the variables are provided herein.

Abstract translation: 式I化合物是HIF脯氨酰羟化酶的有用抑制剂。 式I化合物具有以下结构：（I）其中本文提供变量的定义。

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：WO2015017407A1

公开(公告)日：2015-02-05

申请号：PCT/US2014/048610

申请日：2014-07-29

Applicant: AMGEN INC.

Inventor： LEWIS, Richard T. ,  ALLEN, Jennifer R. ,  BROWN, James ,  GUZMAN-PEREZ, Angel ,  HUA, Zihao ,  JUDD, Ted ,  LIU, Qingyian ,  OLIVIERI, Philip R. ,  SCHENKEL, Laurie ,  STELLWAGEN, John ,  VAIDA, Karina R. ,  WHITE, Ryan

IPC: C07D513/08 ,  C07D519/00 ,  A61K31/547 ,  A61P25/00

CPC classification number: C07D513/08 ,  C07D513/06 ,  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 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.

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。 本发明还提供包含化合物的药物组合物和用于治疗由BACE的生物活性产生的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。 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。

公开(公告)号：WO2008130508A1

公开(公告)日：2008-10-30

申请号：PCT/US2008/004634

申请日：2008-04-09

Applicant: AMGEN INC. ,  ALLEN, Jennifer R. ,  BURLI, Roland ,  GOLDEN, Jennifer E. ,  MULLER, Kristine M. ,  REED, Anthony B.

Inventor： ALLEN, Jennifer R. ,  BURLI, Roland ,  GOLDEN, Jennifer E. ,  MULLER, Kristine M. ,  REED, Anthony B.

IPC: C07D213/16 ,  C07D309/04 ,  C07D333/10 ,  C07C15/24 ,  C07C235/04 ,  A61K31/44 ,  A61K31/381

CPC classification number: C07D213/16 ,  C07D213/56 ,  C07D309/04 ,  C07D309/06 ,  C07D333/10 ,  C07D333/24

Abstract: Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Abstract translation: 式I化合物是HIF脯氨酰羟化酶的有用抑制剂。 式I的化合物具有以下结构：其中本文提供变量的定义。