公开(公告)号：US20240050430A1

公开(公告)日：2024-02-15

申请号：US18213464

申请日：2023-06-23

Applicant: Amgen Inc.

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

IPC: A61K31/517 ,  A61P35/00 ,  A61K31/4985 ,  A61K39/395 ,  C07D403/04 ,  C07D471/04

CPC classification number: A61K31/517 ,  A61P35/00 ,  C07D471/04 ,  A61K39/39558 ,  C07D403/04 ,  A61K31/4985

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：US20180319773A1

公开(公告)日：2018-11-08

申请号：US16033632

申请日：2018-07-12

Applicant: AMGEN INC.

Inventor： Ning CHEN ,  Xiaoqi CHEN ,  Yinhong CHEN ,  Alan C. CHENG ,  Richard V. CONNORS ,  Jeffrey DEIGNAN ,  Paul John DRANSFIELD ,  Xiaohui DU ,  Zice FU ,  Julie Anne HEATH ,  Daniel B. HORNE ,  Jonathan HOUZE ,  Matthew R. KALLER ,  Aarif Yusuf KHAKOO ,  David John KOPECKY ,  Su-Jen LAI ,  Zhihua MA ,  Lawrence R. MCGEE ,  Julio C. MEDINA ,  Jeffrey T. MIHALIC ,  Nobuko NISHIMURA ,  Steven H. OLSON ,  Vatee PATTAROPONG ,  Gayathri SWAMINATH ,  Xiaodong WANG ,  Kevin YANG ,  Wen-Chen YEH ,  Mikkel V. DEBENEDETTO ,  Robert P. FARRELL ,  Simon J. HEDLEY ,  Ted C. JUDD ,  Frank KAYSER

IPC: C07D401/14 ,  C07D401/12 ,  A61K31/437 ,  C07D417/14 ,  A61K45/06 ,  C07B57/00 ,  C07B59/00 ,  C07D211/54 ,  C07D213/71 ,  C07D213/82 ,  C07D239/26 ,  C07D239/30 ,  C07D241/12 ,  C07D241/24 ,  C07D249/08 ,  C07D471/04 ,  C07D413/14 ,  C07D413/04 ,  C07D401/04 ,  C07D213/61 ,  C07D239/34 ,  C07D241/18 ,  C07F7/08 ,  C07D295/16 ,  C07C311/13 ,  A61K31/695 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/513 ,  C07D405/14

CPC classification number: C07D401/14 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/513 ,  A61K31/695 ,  A61K45/06 ,  C07B57/00 ,  C07B59/002 ,  C07B2200/05 ,  C07B2200/07 ,  C07C311/13 ,  C07D211/54 ,  C07D213/61 ,  C07D213/71 ,  C07D213/82 ,  C07D239/26 ,  C07D239/30 ,  C07D239/34 ,  C07D241/12 ,  C07D241/18 ,  C07D241/24 ,  C07D249/08 ,  C07D295/16 ,  C07D401/04 ,  C07D401/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07F7/08

Abstract: Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

公开(公告)号：US20170044131A1

公开(公告)日：2017-02-16

申请号：US15298434

申请日：2016-10-20

Applicant: AMGEN INC.

Inventor： Ning CHEN ,  Xiaoqi CHEN ,  Yinhong CHEN ,  Alan C. CHENG ,  Richard V. CONNORS ,  Jeffrey DEIGNAN ,  Paul John DRANSFIELD ,  Xiaohui DU ,  Zice FU ,  Julie Anne HEATH ,  Daniel B. HORNE ,  Jonathan HOUZE ,  Matthew R. KALLER ,  Aarif Yusuf KHAKOO ,  David John KOPECKY ,  Su-Jen LAI ,  Zhihua MA ,  Lawrence R. MCGEE ,  Julio C. MEDINA ,  Jeffrey T. MIHALIC ,  Nobuko NISHIMURA ,  Steven H. OLSON ,  Vatee PATTAROPONG ,  Gayathri SWAMINATH ,  Xiaodong WANG ,  Kevin YANG ,  Wen-Chen YEH ,  Mikkel V. DEBENEDETTO ,  Robert P. FARRELL ,  Simon J. HEDLEY ,  Ted C. JUDD ,  Frank KAYSER

IPC: C07D401/04 ,  A61K45/06 ,  C07D401/14 ,  A61K31/506 ,  C07D417/14 ,  A61K31/444 ,  A61K31/497 ,  A61K31/513 ,  C07D471/04 ,  A61K31/4439 ,  C07D413/14

CPC classification number: A61K31/506 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/497 ,  A61K31/501 ,  A61K31/513 ,  A61K31/695 ,  A61K45/06 ,  C07B57/00 ,  C07B59/002 ,  C07B2200/05 ,  C07B2200/07 ,  C07C311/13 ,  C07D211/54 ,  C07D213/61 ,  C07D213/71 ,  C07D213/82 ,  C07D239/26 ,  C07D239/30 ,  C07D239/34 ,  C07D241/12 ,  C07D241/18 ,  C07D241/24 ,  C07D249/08 ,  C07D295/16 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07F7/08

Abstract: Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

公开(公告)号：US20230091042A1

公开(公告)日：2023-03-23

申请号：US17788272

申请日：2021-01-08

Applicant: AMGEN INC.

Inventor： Abhisek BANERJEE ,  Victor J. CEE ,  Ning CHEN ,  Xiaofen LI ,  Ryan Paul WURZ

IPC: C07D417/14

Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.

公开(公告)号：US20200207747A1

公开(公告)日：2020-07-02

申请号：US16466211

申请日：2017-12-13

Applicant: AMGEN INC.

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

IPC: C07D413/10 ,  C07D413/14 ,  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, R2, R2′, R3, R4, R5, R6, and R7 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：US20150307521A1

公开(公告)日：2015-10-29

申请号：US14435516

申请日：2013-11-12

Applicant: AMGEN INC.

Inventor： Ryan WHITE ,  Oleg EPSTEIN ,  Jason B. HUMAN ,  Xiao Mei ZHENG ,  Yuan CHENG ,  Kelvin SHAM ,  Qingyian Liu ,  Ning CHEN

IPC: C07D519/00 ,  C07D491/052 ,  C07D513/20 ,  C07D498/10 ,  C07D513/10 ,  C07D311/80 ,  C07D498/20

CPC classification number: C07D519/00 ,  C07D311/80 ,  C07D491/052 ,  C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  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 A1, A2, A3, A4, A5, A6, L, R2, R7, 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中的A1，A2，A3，A4，A5，A6，L，R2，R7，X，Y和Z如本文所定义。 本发明还包括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：US20250122222A1

公开(公告)日：2025-04-17

申请号：US18695673

申请日：2022-08-10

Applicant: AMGEN INC.

Inventor： Michael M. YAMANO ,  Yunxiao LI ,  Primali Vasundera NAVARATNE ,  Jose M. MEDINA ,  Ning CHEN ,  Liping PETTUS ,  Rene RAHIMOFF ,  Xiaofen LI ,  John STELLWAGEN ,  Francesco MANONI ,  Kexue LI ,  Brian Alan LANMAN ,  Ryan Paul Wurz ,  Wei ZHAO ,  Huan RUI ,  Josephine ESHON

IPC: C07D519/00 ,  A61K31/519 ,  A61K31/5386 ,  A61K31/541 ,  A61K31/553 ,  A61K31/554 ,  C07D471/04

Abstract: The present disclosure provides compounds useful for the inhibition of KRAS. 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, cancer.

公开(公告)号：US20250034167A1

公开(公告)日：2025-01-30

申请号：US18695693

申请日：2022-08-10

Applicant: AMGEN INC.

Inventor： Michael M. YAMANO ,  Yunxiao LI ,  Primali Vasundera NAVARATNE ,  Jose M. MEDINA ,  Ning CHEN ,  Liping PETTUS ,  Rene RAHIMOFF ,  Xiaofen LI ,  John STELLWAGEN ,  Francesco MANONI ,  Kexue LI ,  Brian Alan LANMAN ,  Ryan Paul Wurz ,  Wei ZHAO ,  Huan RUI ,  Josephine ESHON

IPC: C07D519/00 ,  A61K31/519 ,  A61K31/55

Abstract: The present disclosure provides compounds useful for the inhibition of KRAS G12D. 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, cancer.

公开(公告)号：US20240294551A1

公开(公告)日：2024-09-05

申请号：US18614911

申请日：2024-03-25

Applicant: AMGEN INC.

Inventor： Ryan Paul Wurz ,  Yunxiao LI ,  Primali Vasundera NAVARATNE ,  Jose M. MEDINA ,  Ning CHEN ,  Liping PETTUS ,  Xiaofen LI ,  John STELLWAGEN ,  Kexue LI ,  Brian Alan LANMAN ,  Michael M. YAMANO ,  Wei ZHAO ,  Benjamin WIGMAN ,  Fabien EMMETIERE ,  Albert K. AMEGADZIE ,  Christopher P. MOHR ,  Aaron C. SIEGMUND ,  Rene RAHIMOFF ,  Zhichen WU ,  Adriano BAUER ,  Andrew SMALIGO ,  Quentin Tercenio ,  Qingyian Liu ,  Shon K. Booker

IPC: C07D519/00 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/55 ,  A61K31/551 ,  A61K31/553 ,  C07D471/22 ,  C07D498/22 ,  C07D513/22

CPC classification number: C07D519/00 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/55 ,  A61K31/551 ,  A61K31/553 ,  C07D471/22 ,  C07D498/22 ,  C07D513/22

Abstract: The present disclosure provides compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G13D, Q61H, Q61L or G12C. 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, cancer.

公开(公告)号：US20240287068A1

公开(公告)日：2024-08-29

申请号：US18640641

申请日：2024-04-19

Applicant: Amgen Inc.

Inventor： Brian Alan LANMAN ,  Shon BOOKER ,  Clifford GOODMAN ,  Anthony B. REED ,  Jonathan D. LOW ,  Hui-Ling WANG ,  Ning CHEN ,  Ana Elena MINATTI ,  Ryan WURZ ,  Victor J. CEE

IPC: C07D471/04 ,  A61K31/519 ,  A61K31/7068 ,  A61K38/07 ,  A61P35/00

CPC classification number: C07D471/04 ,  A61K31/519 ,  A61P35/00 ,  A61K31/7068 ,  A61K38/07 ,  A61K2300/00

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.