公开(公告)号：US10906890B2

公开(公告)日：2021-02-02

申请号：US16347955

申请日：2017-11-03

Applicant: AMGEN INC.

Inventor： Ning Chen ,  Yinhong Chen ,  Mikkel V. Debenedetto ,  Paul John Dransfield ,  James S. Harvey ,  Julie Anne Heath ,  Jonathan Houze ,  Aarif Yusuf Khakoo ,  Su-Jen Lai ,  Zhihua Ma ,  Nobuko Nishimura ,  Vatee Pattaropong ,  Gayathri Swaminath ,  Wen-Chen Yeh ,  Charles Kreiman

IPC: C07D403/14 ,  C07D239/24 ,  C07D241/12 ,  C07D249/14 ,  C07D401/04 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D417/12 ,  C07D417/14 ,  C07D239/26 ,  A61P9/04 ,  C07D401/14

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 may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: (I), (II) where the definitions of the variables are provided herein.

公开(公告)号：US09868721B2

公开(公告)日：2018-01-16

申请号：US15297272

申请日：2016-10-19

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

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：US09845310B2

公开(公告)日：2017-12-19

申请号：US15298748

申请日：2016-10-20

Applicant: AMGEN INC.

Inventor： Ning Chen ,  Xiaoqi 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 ,  David John Kopecky ,  Su-Jen Lai ,  Zhihua Ma ,  Lawrence R. McGee ,  Julio C. Medina ,  Jeffrey T. Mihalic ,  Nobuko Nishimura ,  Steven H. Olson ,  Vatee Pattaropong ,  Xiaodong Wang ,  Kevin Yang ,  Mikkel V. Debenedetto ,  Simon J. Hedley

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

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 VII, salts thereof, tautomers thereof, and salts of the tautomers are useful intermediates in the synthesis of agonists of the APJ Receptor. Compounds of Formula VII have the following structure: where the definitions of the variables are provided herein.

公开(公告)号：US09573936B2

公开(公告)日：2017-02-21

申请号：US15158174

申请日：2016-05-18

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 ,  A61K45/06 ,  C07D213/82 ,  C07D241/24 ,  C07D239/30 ,  C07D239/26 ,  C07D401/04 ,  A61K31/4439 ,  A61K31/506 ,  C07D413/14 ,  C07B59/00 ,  A61K31/497 ,  A61K31/513 ,  C07D471/04 ,  A61K31/444 ,  C07D417/14 ,  C07B57/00 ,  C07D405/14 ,  A61K31/501 ,  C07D249/08 ,  C07D241/12 ,  C07D213/71 ,  C07D211/54

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.

Abstract translation: 其中在这里提供变量的定义。

公开(公告)号：US20170042871A1

公开(公告)日：2017-02-16

申请号：US15297487

申请日：2016-10-19

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: A61K31/4439 ,  A61K31/501 ,  A61K31/444 ,  A61K31/506 ,  A61K31/497

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：US09296734B2

公开(公告)日：2016-03-29

申请号：US14192710

申请日：2014-02-27

Applicant: AMGEN INC.

Inventor： Ana Elena Minatti ,  Jonathan D. Low ,  Jennifer R. Allen ,  Jian Chen ,  Ning Chen ,  Yuan Cheng ,  Ted Judd ,  Qingyian Liu ,  Patricia Lopez ,  Wenyuan Qian ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Nuria A. Tamayo ,  Qiufen Xue ,  Bryant Yang ,  Wenge Zhong

IPC: C07D413/14 ,  C07D413/12 ,  C07D471/04 ,  C07D513/04 ,  C07F7/08 ,  C07D413/04 ,  C07D413/10 ,  C07D265/08 ,  C07D498/04

CPC classification number: C07D413/14 ,  C07D265/08 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F7/0812

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 A4, A5, A6, A8, each of R1 and R2, R3 and R7 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 Formulas II and III, and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III.

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中的各个R 1和R 2，R 3和R 7各自独立地定义的变量A4，A5，A6，A8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和III的化合物及其分式实施方案，可用于制备式I-III化合物的中间体和方法和方法。