公开(公告)号：WO2022169948A1

公开(公告)日：2022-08-11

申请号：PCT/US2022/015076

申请日：2022-02-03

Applicant: AMGEN INC.

Inventor： AMEGADZIE, Albert ,  BEYLKIN, Diane Jennifer ,  BOOKER, Shon ,  BOURBEAU, Matthew Paul ,  BUTLER, John R. ,  GREENMAN, Kevin Lloyd ,  KOHN, Todd J. ,  LI, Kexue ,  LIU, Qingyian ,  MINATTI, Ana Elena ,  NAVARATNE, Primali Vasundera ,  PETTUS, Liping H. ,  RAHIMOFF, Rene ,  WANG, Hui-Ling ,  WEIRES, Nicholas Anthony

IPC: C07D471/04 ,  C07D471/14 ,  C07D491/048 ,  C07D491/052 ,  C07D491/147 ,  C07D495/04 ,  C07D498/04 ,  C07D519/00 ,  C07B59/00 ,  A61K31/55 ,  A61K31/4375 ,  A61K31/519 ,  A61K31/4355 ,  A61K31/437 ,  A61K31/4365 ,  A61P35/00

Abstract: Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure:

公开(公告)号：WO2019213526A1

公开(公告)日：2019-11-07

申请号：PCT/US2019/030606

申请日：2019-05-03

Applicant: AMGEN INC.

Inventor： WURZ, Ryan Paul ,  CEE, Victor, J. ,  AMEGADZIE, Albert ,  CHEN, Ning ,  LANMAN, Brian, Alan ,  BARTBERGER, Michael, D.

IPC: C07F9/6561 ,  A61K31/553 ,  A61K45/06

Abstract: Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

公开(公告)号：WO2021163344A1

公开(公告)日：2021-08-19

申请号：PCT/US2021/017682

申请日：2021-02-11

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer Rebecca ,  AMEGADZIE, Albert ,  BEYLKIN, Diane Jennifer ,  BOOKER, Shon ,  BOURBEAU, Matthew Paul ,  BUTLER, John R. ,  FROHN, Michael J. ,  GLAD, Sanne Ormholt Schroder ,  HUSEMOEN, Birgitte Weinreich ,  KALLER, Matthew R. ,  KOHN, Todd J. ,  LANMAN, Brian Alan ,  LI, Kexue ,  LIU, Qingyian ,  LOPEZ, Patricia ,  MA, Vu Van ,  MANONI, Francesco ,  MEDINA, Jose ,  MINATTI, Ana Elena ,  PEIRO CADAHIA, Jorge ,  PETTUS, Liping ,  PICKRELL, Alexander J. ,  SARVARY, Ian ,  TAMAYO, Nuria A. ,  VESTERGAARD, Mikkel

IPC: C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  A61P35/00 ,  A61K31/435

Abstract: Described herein are compounds of Formula I and pharmaceutically acceptable salt thereof, stereoisomers, tautomers as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders. Compounds of Formula I have the following structure: (I)

公开(公告)号：WO2019213516A1

公开(公告)日：2019-11-07

申请号：PCT/US2019/030593

申请日：2019-05-03

Applicant: AMGEN INC.

Inventor： ALLEN, John Gordon ,  ALLEN, Jennifer Rebecca ,  MINATTI, Ana Elena ,  XUE, Qiufen ,  WURZ, Ryan Paul ,  TEGLEY, Christopher M. ,  PICKRELL, Alexander J. ,  NGUYEN, Thomas T. ,  MA, Vu Van ,  LOPEZ, Patricia ,  LIU, Longbin ,  KOPECKY, David John ,  FROHN, Michael J. ,  CHEN, Ning ,  CHEN, Jian Jeffrey ,  SIEGMUND, Aaron C. ,  AMEGADZIE, Albert ,  TAMAYO, Nuria A. ,  BOOKER, Shon ,  GOODMAN, Clifford ,  WALTON, Mary ,  NISHIMURA, Nobuko ,  SHIN, Youngsook ,  LOW, Jonathan D. ,  CEE, Victor J. ,  REED, Anthony B. ,  WANG, Hui-Ling ,  LANMAN, Brian Alan

IPC: C07D403/04 ,  C07D403/14 ,  C07D471/04 ,  C07D487/04 ,  A61P35/00 ,  A61K31/519

Abstract: Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

公开(公告)号：WO2013130890A1

公开(公告)日：2013-09-06

申请号：PCT/US2013/028436

申请日：2013-02-28

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer R. ,  AMEGADZIE, Albert ,  ANDREWS, Kristin L. ,  BROWN, James ,  CHEN, Jian J. ,  CHEN, Ning ,  HARRINGTON, Essa Hu ,  LIU, Qingyian ,  NGUYEN, Thomas T. ,  PICKRELL, Alexander J. ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  YUAN, Chester Chenguang ,  ZHONG, Wenge

IPC: C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D473/30 ,  C07D473/34 ,  C07D473/40 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  A61K31/437 ,  A61P25/18

CPC classification number: C07D487/04 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D473/30 ,  C07D473/34 ,  C07D473/40 ,  C07D498/04 ,  C07D513/04 ,  C07D519/00

Abstract: Heterobicyclic compounds of Formula (I): (I); or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, 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, Huntington's Disease, and the like.

Abstract translation: 式（I）的杂双环化合物：（I）; 或其药学上可接受的盐，互变异构体或立体异构体，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，非胰岛素依赖性糖尿病，精神分裂症，双相情感障碍，强迫症，亨廷顿舞蹈病等。

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：WO2017024180A1

公开(公告)日：2017-02-09

申请号：PCT/US2016/045650

申请日：2016-08-04

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer, R. ,  AMEGADZIE, Albert ,  BOURBEAU, Matthew, P. ,  BROWN, James, A. ,  CHEN, Ning ,  FROHN, Michael, J. ,  LIU, Longbin ,  LIU, Qingyian ,  PETTUS, Liping, H. ,  QIAN, Wenyuan ,  REEVES, Corey, M. ,  SIEGMUND, Aaron, C.

IPC: A61K31/5415 ,  A61P25/28 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D491/056 ,  C07D279/08

CPC classification number: C07D417/10 ,  C07D279/08 ,  C07D417/14 ,  C07D471/04 ,  C07D491/056

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 7 , and each of R a , R b , R 1 , R 2 , R 3 , R 8 R 9 and R 10 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 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, 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中的变量A4，A5，A6，A7以及式I的R a，R b，R 1，R 2，R 3，R 8 R 9和R 10各自独立地定义。 本发明还提供包含该化合物的药物组合物，以及由BACE的生物活性产生的化合物和组合物用于治疗与Aβ斑块形成和沉积相关的病症和/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。

公开(公告)号：WO2009075874A1

公开(公告)日：2009-06-18

申请号：PCT/US2008/013639

申请日：2008-12-12

Applicant: AMGEN INC. ,  HITCHCOCK, Stephen ,  CHEN, Jian J. ,  NCUBE, Mqhele ,  NIXEY, Thomas ,  AMEGADZIE, Albert ,  KUNZ, Roxanne ,  QIAN, Wenyuan ,  CHEN, Ning ,  TEGLEY, Christopher M. ,  DEMORIN, Frenel ,  YUAN, Chester Chenguang ,  LIU, Qingyian ,  ZHU, Jiawang ,  PETERKIN, Tanya ,  ADAMS, Jeffrey A. ,  HU, Essa ,  CHAVEZ, JR., Frank

Inventor： HITCHCOCK, Stephen ,  CHEN, Jian J. ,  NCUBE, Mqhele ,  NIXEY, Thomas ,  AMEGADZIE, Albert ,  KUNZ, Roxanne ,  QIAN, Wenyuan ,  CHEN, Ning ,  TEGLEY, Christopher M. ,  DEMORIN, Frenel ,  YUAN, Chester Chenguang ,  LIU, Qingyian ,  ZHU, Jiawang ,  PETERKIN, Tanya ,  ADAMS, Jeffrey A. ,  HU, Essa ,  CHAVEZ, JR., Frank

IPC: C07D213/40 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D413/12 ,  A61K31/00 ,  A61P25/28

CPC classification number: C07D213/40 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D413/12

Abstract: The present invention provides compounds that are gamma secretase modulators and are therefore useful for the treatment of diseases treatable by modulation of gamma secretase such as Alzheimer's disease. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Abstract translation: 本发明提供了γ-分泌酶调节剂的化合物，因此可用于治疗通过调节γ-分泌酶如阿尔茨海默病可治疗的疾病。 还提供含有这些化合物的药物组合物和制备这些化合物的方法。

公开(公告)号：WO2022115377A1

公开(公告)日：2022-06-02

申请号：PCT/US2021/060332

申请日：2021-11-22

Applicant: AMGEN INC.

Inventor： AMEGADZIE, Albert ,  BEYLKIN, Diane Jennifer ,  BOOKER, Shon ,  BOURBEAU, Matthew Paul ,  BUTLER, John R. ,  GLAD, Sanne Omholt Schroder ,  KOHN, Todd J. ,  LANMAN, Brian Alan ,  LI, Kexue ,  LIU, Qingyian ,  LOPEZ, Patricia ,  MANONI, Francesco ,  NAVARATNE, Primali Vasundera ,  PETTUS, Liping H. ,  RAHIMOFF, Rene ,  TAMAYO, Nuria A. ,  VESTERGAARD, Mikkel ,  WANG, Hui-Ling ,  WEIRES, Nicholas Anthony

IPC: C07D471/04 ,  A61K31/4355 ,  A61K31/437 ,  A61K31/501 ,  A61P35/00 ,  C07D491/048 ,  C07D491/147 ,  C07D471/14 ,  C07D498/04 ,  C07D401/14 ,  C07D401/12 ,  C07D495/04

Abstract: Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formule (I).

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).