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：WO2020132653A1

公开(公告)日：2020-06-25

申请号：PCT/US2019/068174

申请日：2019-12-20

Applicant: AMGEN INC.

Inventor： TAMAYO, Nuria A. ,  BANERJEE, Abhisek ,  FROHN, Michael J. ,  CHEN, Jian Jeffrey ,  LI, Kexue ,  BOURBEAU, Matthew Paul ,  JIA, Lei ,  KALLER, Matthew Richard ,  NGUYEN, Thomas T. ,  NISHIMURA, Nobuko ,  XUE, Qiufen May ,  ALLEN, John Gordon

IPC: C07D221/20 ,  C07D401/14 ,  C07D413/14 ,  A61P35/00 ,  A61K31/497 ,  C07D405/14 ,  C07D491/08 ,  C07D491/107

Abstract: The present invention relates to chemical compounds having a general formula (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

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：WO2020132648A1

公开(公告)日：2020-06-25

申请号：PCT/US2019/068169

申请日：2019-12-20

Applicant: AMGEN INC.

Inventor： TAMAYO, Nuria A. ,  BANERJEE, Abhisek ,  BROWN, James Alexander ,  FROHN, Michael J. ,  CHEN, Jian Jeffrey ,  LI, Kexue ,  LIU, Qingyian ,  LOW, Jonathan Dante ,  MA, Vu ,  PETTUS, Liping H. ,  WALTON, Mary Catherine ,  MINATTI, Ana Elena ,  BOURBEAU, Matthew Paul ,  JIA, Lei

IPC: A61P35/00 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  A61K31/506 ,  C07D419/14 ,  C07D491/044

Abstract: Compounds of formula (I): (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

公开(公告)号：WO2015191781A2

公开(公告)日：2015-12-17

申请号：PCT/US2015/035205

申请日：2015-06-10

Applicant: AMGEN INC.

Inventor： HOLDER, Jerry Ryan ,  SWAMINATH, Gayathri ,  FROHN, Michael J. ,  LANMAN, Brian Alan ,  REED, Anthony B. ,  MIRANDA, Leslie P. ,  ALLEN, John Gordon ,  PICKRELL, Alexander J. ,  SIEGMUND, Aaron C. ,  PENNINGTON, Lewis D. ,  YANG, Bryant

CPC classification number: C07K7/08 ,  A61K38/00 ,  A61K38/10 ,  A61K47/542 ,  A61K47/60 ,  C07K14/47 ,  C07K2319/30

Abstract: The invention provides modified apelin polypeptides having increased stability, circulating half-life, and/or potency relative to the native apelin-13 polypeptide. Compositions comprising the modified apelin polypeptides and methods of using the polypeptides for treating cardiac disorders, such as heart failure, are also disclosed.

Abstract translation: 本发明提供了相对于天然apelin-13多肽具有增加的稳定性，循环半衰期和/或效力的修饰的apelin多肽。 还公开了包含修饰的apelin多肽的组合物和使用该多肽治疗心脏病症如心力衰竭的方法。

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：WO2023004075A1

公开(公告)日：2023-01-26

申请号：PCT/US2022/037928

申请日：2022-07-21

Applicant: AMGEN INC.

Inventor： WU, Tian ,  AGARWAL, Prashant ,  ROTHELI, Andreas R. ,  PARK, Hyunsoo ,  FROHN, Michael J.

IPC: C07D401/14 ,  A61P35/00 ,  A61K31/506

Abstract: Disclosed herein is a salt, a crystalline anhydrous form, a hydrate, a solvate, or a co-crystal of a free base compound 2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-[(2-hydroxyethanesulfonyl)amino]benzamide (Compound A); method of preparation, pharmaceutical compositions, and method of treating a disease mediated by a motor protein kinesin family member 18A (KIF18A) inhibition, wherein said disease is a neoplastic disease, including a cancer or a tumor.

公开(公告)号：WO2020132651A1

公开(公告)日：2020-06-25

申请号：PCT/US2019/068172

申请日：2019-12-20

Applicant: AMGEN INC.

Inventor： TAMAYO, Nuria A. ,  BANERJEE, Abhisek ,  BROWN, James Alexander ,  FROHN, Michael J. ,  CHEN, Jian Jeffrey ,  LI, Kexue ,  LIU, Qingyian ,  LOW, Jonathan Dante ,  MA, Vu ,  PETTUS, Liping H. ,  WALTON, Mary Catherine ,  MINATTI, Ana Elena ,  BOURBEAU, Matthew Paul ,  JIA, Lei ,  NGUYEN, Thomas T. ,  NISHIMURA, Nobuko ,  XUE, Qiufen May ,  ALLEN, John Gordon

IPC: A61P35/00 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  A61K31/497 ,  A61K31/444

Abstract: Compounds of formula (I): (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

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.