公开(公告)号：US09296736B2

公开(公告)日：2016-03-29

申请号：US14316586

申请日：2014-06-26

Applicant: AMGEN INC.

Inventor： Michael D. Bartberger ,  Ana Gonzalez Buenrostro ,  Hilary Plake Beck ,  Xiaoqi Chen ,  Richard Victor Connors ,  Jeffrey Deignan ,  Jason A. Duquette ,  John Eksterowicz ,  Benjamin Fisher ,  Brian M. Fox ,  Jiasheng Fu ,  Zice Fu ,  Felix Gonzalez Lopez De Turiso ,  Michael W. Gribble ,  Darin J. Gustin ,  Julie A. Heath ,  Xin Huang ,  XianYun Jiao ,  Michael G. Johnson ,  Frank Kayser ,  David John Kopecky ,  SuJen Lai ,  Yihong Li ,  Zhihong Li ,  Jiwen Liu ,  Jonathan D. Low ,  Brian S. Lucas ,  Zhihua Ma ,  Lawrence R. McGee ,  Joel McIntosh ,  Dustin L. McMinn ,  Julio C. Medina ,  Jeffrey Thomas Mihalic ,  Steven H. Olson ,  Yosup Rew ,  Philip M. Roveto ,  Daqing Sun ,  Xiaodong Wang ,  Yingcai Wang ,  Xuelei Yan ,  Ming Yu ,  Jiang Zhu

IPC: C07D279/02 ,  C07D417/12 ,  C07D211/76 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D407/04 ,  C07D407/06 ,  C07D409/04 ,  C07D413/06 ,  C07D417/06 ,  C07D471/10 ,  C07D498/08 ,  C07D498/20 ,  C07D405/04 ,  C07D417/14 ,  C07D491/08 ,  C07D491/153

CPC classification number: C07D211/76 ,  C07D221/20 ,  C07D279/02 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D407/04 ,  C07D407/06 ,  C07D409/04 ,  C07D409/12 ,  C07D413/06 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/10 ,  C07D491/08 ,  C07D491/153 ,  C07D498/08 ,  C07D498/14 ,  C07D498/20

Abstract: The present invention provides MDM2 inhibitor compounds of Formula I, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

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。

公开(公告)号：US09085576B2

公开(公告)日：2015-07-21

申请号：US14199844

申请日：2014-03-06

Applicant: AMGEN INC.

Inventor： Ana Elena Minatti ,  Jonathan D. Low ,  Jennifer R. Allen ,  Albert Amegadzie ,  James Brown ,  Michael J. Frohn ,  Angel Guzman-Perez ,  Paul E. Harrington ,  Patricia Lopez ,  Vu Van Ma ,  Nobuko Nishimura ,  Wenyuan Qian ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Kelvin Sham ,  Adrian L. Smith ,  Ryan White ,  Qiufen Xue

IPC: C07D471/04 ,  C07D265/12 ,  C07D417/12 ,  C07D417/14 ,  C07D413/12 ,  C07D413/14 ,  A61K31/537 ,  C07D413/10 ,  C07D491/048

CPC classification number: C07D413/12 ,  C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

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 Ra, Rb, R1, R2, R3 and R7 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 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 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中的每个R a，R b，R 1，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，以及该化合物和组合物用于治疗由BACE的生物学活性产生的与A-β斑块形成和沉积有关的病症和/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：US20240300892A1

公开(公告)日：2024-09-12

申请号：US18484675

申请日：2023-10-11

Applicant: Amgen Inc.

Inventor： Michael D. Bartberger ,  Ana Gonzalez Buenrostro ,  Hilary Plake Beck ,  Xiaoqi Chen ,  Richard Victor Connors ,  Jeffrey Deignan ,  Jason A. Duquette, I ,  John Eksterowicz ,  Benjamin Fisher ,  Brian M. Fox ,  Jiasheng Fu ,  Zice Fu ,  Felix Gonzalez Lopez De Turiso ,  Michael W. Gribble ,  Darin J. Gustin ,  Julie A. Heath ,  Xin Huang ,  XianYun Jiao ,  Michael G. Johnson ,  Frank Kayser ,  David John Kopecky ,  SuJen Lai ,  Yihong Li ,  Zhihong Li ,  Jiwen Liu ,  Jonathan D. Low ,  Brian S. Lucas ,  Zhihua MA ,  Lawrence R. McGee ,  Joel McIntosh ,  Dustin L. McMinn ,  Julio C. Medina ,  Jeffrey Thomas Mihalic ,  Steven H. Olson ,  Yossup Rew ,  Philip M. Roveto ,  Daqing Sun ,  Xiaodong Wang ,  Yingcai Wang ,  Xuelei Yan ,  Ming Yu ,  Jiang Zhu

IPC: C07D211/76 ,  C07D221/20 ,  C07D279/02 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D407/04 ,  C07D407/06 ,  C07D409/04 ,  C07D409/12 ,  C07D413/06 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/10 ,  C07D491/08 ,  C07D491/153 ,  C07D498/08 ,  C07D498/14 ,  C07D498/20

CPC classification number: C07D211/76 ,  C07D221/20 ,  C07D279/02 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D407/04 ,  C07D407/06 ,  C07D409/04 ,  C07D409/12 ,  C07D413/06 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/10 ,  C07D491/08 ,  C07D491/153 ,  C07D498/08 ,  C07D498/14 ,  C07D498/20

Abstract: The present invention provides MDM2 inhibitor compounds of Formula I,






wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

公开(公告)号：US12083121B2

公开(公告)日：2024-09-10

申请号：US17579359

申请日：2022-01-19

Applicant: AMGEN INC.

Inventor： John Gordon Allen ,  Brian Alan Lanman ,  Jian Chen ,  Anthony B. Reed ,  Victor J. Cee ,  Longbin Liu ,  Patricia Lopez ,  Ryan Paul Wurz ,  Thomas T. Nguyen ,  Shon Booker ,  Jennifer Rebecca Allen ,  Margaret Chu-Moyer ,  Albert Amegadzie ,  Ning Chen ,  Clifford Goodman ,  Jonathan D. Low ,  Vu Van Ma ,  Ana Elena Minatti ,  Nobuko Nishimura ,  Alexander J. Pickrell ,  Hui-Ling Wang ,  Youngsook Shin ,  Aaron C. Siegmund ,  Kevin C. Yang ,  Nuria A. Tamayo ,  Mary Walton ,  Qiufen Xue

IPC: C07D241/04 ,  A61K31/519 ,  A61K31/551 ,  A61K39/395 ,  A61P35/00

CPC classification number: A61K31/519 ,  A61K31/551 ,  A61K39/39558 ,  A61P35/00

Abstract: Provided herein are KRAS G12C inhibitors, such as




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：US11993597B2

公开(公告)日：2024-05-28

申请号：US17692026

申请日：2022-03-10

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 ,  A61P35/00 ,  A61K31/7068 ,  A61K38/07

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.

公开(公告)号：US11766436B2

公开(公告)日：2023-09-26

申请号：US17363878

申请日：2021-06-30

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 ,  A61K31/4985 ,  A61K39/39558 ,  A61P35/00 ,  C07D403/04 ,  C07D471/04

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：US11306087B2

公开(公告)日：2022-04-19

申请号：US16817109

申请日：2020-03-12

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 ,  A61P35/00 ,  A61K31/519 ,  A61K31/7068 ,  A61K38/07

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

公开(公告)号：US11285156B2

公开(公告)日：2022-03-29

申请号：US16438349

申请日：2019-06-11

Applicant: Amgen Inc.

Inventor： John Gordon Allen ,  Brian Alan Lanman ,  Jian Chen ,  Anthony B. Reed ,  Victor J. Cee ,  Longbin Liu ,  Patricia Lopez ,  Ryan Paul Wurz ,  Thomas T. Nguyen ,  Shon Booker ,  Jennifer Rebecca Allen ,  Margaret Chu-Moyer ,  Albert Amegadzie ,  Ning Chen ,  Clifford Goodman ,  Jonathan D. Low ,  Vu Van Ma ,  Ana Elena Minatti ,  Nobuko Nishimura ,  Alexander J. Pickrell ,  Hui-Ling Wang ,  Youngsook Shin ,  Aaron C. Siegmund ,  Kevin C. Yang ,  Nuria A. Tamayo ,  Mary Walton ,  Qiufen Xue

IPC: A61K31/497 ,  C07D241/04 ,  A61K31/519 ,  A61K31/551 ,  A61K39/395 ,  A61P35/00

Abstract: Provided herein are KRAS G12C inhibitors, such as 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：US11279712B2

公开(公告)日：2022-03-22

申请号：US16642441

申请日：2018-08-27

Applicant: AMGEN INC.

Inventor： Sean P. Brown ,  Yunxiao Li ,  Paul E. Harrington ,  Brian Alan Lanman ,  Jonathan D. Low ,  Ana Elena Minatti ,  Vu Van Ma ,  Kexue Li

IPC: C07D513/04 ,  C07D513/08 ,  C07D519/00 ,  A61P35/00 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/7068

Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stenoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.