公开(公告)号：US10246429B2

公开(公告)日：2019-04-02

申请号：US15749895

申请日：2016-08-04

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Albert Amegadzie ,  Matthew P. Bourbeau ,  James A. Brown ,  Ning Chen ,  Michael J. Frohn ,  Longbin Liu ,  Qingyian Liu ,  Liping H. Pettus ,  Wenyuan Qian ,  Corey M. Reeves ,  Aaron C. Siegmund

IPC: C07D417/10 ,  C07D279/08 ,  C07D417/14 ,  C07D471/04 ,  C07D491/056 ,  A61P25/28 ,  A61P25/00 ,  A61P25/16 ,  C07D491/08 ,  C07D491/107 ,  C07D498/10 ,  C07F7/08

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, A7, and each of Ra, Rb, R1, R2, R3, R8 R9 and R10 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.

公开(公告)号：US11845760B2

公开(公告)日：2023-12-19

申请号：US17552016

申请日：2021-12-15

Applicant: AMGEN INC.

Inventor： Shon Booker ,  Matthew Paul Bourbeau ,  John R. Butler ,  Sanne Ormholt Schroder Glad ,  Brian Alan Lanman ,  Patricia Lopez ,  Francesco Manoni ,  Liping H. Pettus ,  Ian Sarvary ,  Nuria A. Tamayo ,  Mikkel Vestergaard ,  Nicholas Anthony Weires

IPC: C07D471/04 ,  C07D471/14 ,  C07D491/04 ,  C07D491/14 ,  C07D495/04 ,  A61K31/4355 ,  A61K31/436 ,  A61K31/4365 ,  A61K31/437 ,  A61K31/4375 ,  A61P35/00 ,  C07D491/06 ,  C07D471/06 ,  C07D471/16 ,  C07D491/16

CPC classification number: C07D491/06 ,  A61P35/00 ,  C07D471/06 ,  C07D471/16 ,  C07D491/16

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：US11021493B2

公开(公告)日：2021-06-01

申请号：US16466207

申请日：2017-12-13

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Matthew P. Bourbeau ,  James A. Brown ,  Ning Chen ,  Michael J. Frohn ,  Zice Fu ,  Longbin Liu ,  Qingyian Liu ,  Liping H. Pettus ,  Wenyuan Qian ,  Corey Reeves ,  Aaron C. Siegmund

IPC: C07D513/08 ,  A61P25/28 ,  C07D417/10

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: wherein variables A, X, 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 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：US08772480B2

公开(公告)日：2014-07-08

申请号：US13681230

申请日：2012-11-19

Applicant: Amgen Inc.

Inventor： Kristin L. Andrews ,  Yunxin Y. Bo ,  Shon Booker ,  Victor J. Cee ,  Noel D'Angelo ,  Bradley J. Herberich ,  Fang-Tsao Hong ,  Claire L. M. Jackson ,  Brian Alan Lanman ,  Hongyu Liao ,  Longbin Liu ,  Nobuko Nishimura ,  Mark H. Norman ,  Liping H. Pettus ,  Anthony B. Reed ,  Adrian Leonard Smith ,  Seifu Tadesse ,  Nuria A. Tamayo ,  Bin Wu ,  Ryan Wurz ,  Kevin C. Yang

IPC: C07D401/04 ,  C07D401/14 ,  A61K31/444 ,  A61K31/53 ,  A61P35/00

CPC classification number: C07D473/00 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

Abstract translation: 本发明涉及式I化合物或其药学上可接受的盐; 使用该化合物治疗疾病或病症如癌症的方法; 和含有这些化合物的药物组合物，其中变量如本文所定义。

公开(公告)号：US11548903B2

公开(公告)日：2023-01-10

申请号：US16466202

申请日：2017-12-13

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Matthew P. Bourbeau ,  Ning Chen ,  Qingyian Liu ,  Liping H. Pettus ,  Aaron C. Siegmund

IPC: C07D513/04 ,  C07D498/04 ,  A61P25/28

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): (Formula (I)) wherein variables X, Y, R2, R3, R4, R5, R6, and n 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：US09550762B2

公开(公告)日：2017-01-24

申请号：US14819256

申请日：2015-08-05

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Albert Amegadzie ,  Matthew P. Bourbeau ,  James A. Brown ,  Jian J. Chen ,  Yuan Cheng ,  Michael J. Frohn ,  Angel Guzman-Perez ,  Paul E. Harrington ,  Longbin Liu ,  Qingyian Liu ,  Jonathan D. Low ,  Vu Van Ma ,  James Manning ,  Ana Elena Minatti ,  Thomas T. Nguyen ,  Nobuko Nishimura ,  Mark H. Norman ,  Liping H. Pettus ,  Alexander J. Pickrell ,  Wenyuan Qian ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Aaron C. Siegmund ,  Markian M. Stec ,  Ryan D. White ,  Qiufen Xue

IPC: C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10 ,  C07D417/04 ,  C07D279/08

CPC classification number: C07D417/12 ,  C07D279/08 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10

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, and 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。 所述化合物具有通式I：其中式I中的变量A4，A5，A6，A8以及R 1，R b，R 1，R 2，R 3和R 7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：US12054476B2

公开(公告)日：2024-08-06

申请号：US17551105

申请日：2021-12-14

Applicant: AMGEN INC.

Inventor： Nuria A. Tamayo ,  Abhisek Banerjee ,  James Alexander Brown ,  Michael J Frohn ,  Jian Jeffrey Chen ,  Kexue Li ,  Qingyian Liu ,  Jonathan Dante Low ,  Vu Ma ,  Liping H. Pettus ,  Mary Catherine Walton ,  Ana Elena Minatti ,  Matthew Paul Bourbeau ,  Lei Jia

IPC: C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14 ,  C07D419/14 ,  C07D491/107

CPC classification number: C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14 ,  C07D419/14 ,  C07D491/107

Abstract: Compounds of 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：US09394297B2

公开(公告)日：2016-07-19

申请号：US14380918

申请日：2013-02-27

Applicant: AMGEN INC.

Inventor： Victor Cee ,  Frank Chavez, Jr. ,  Jian J. Chen ,  Essa Hu Harrington ,  Bradley Herberich ,  Claire L. M. Jackson ,  Brian A. Lanman ,  Thomas T. Nguyen ,  Mark H. Norman ,  Liping H. Pettus ,  Anthony B. Reed ,  Adrian L. Smith ,  Nuria A. Tamayo ,  Andrew Tasker ,  Hui-Ling Wang ,  Bin Wu ,  Ryan Wurz

IPC: C07D401/04 ,  C07D471/04 ,  C07D487/04

CPC classification number: C07D471/04 ,  C07D401/04 ,  C07D487/04

Abstract: The invention relates to amide-containing compounds of formula (1), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

Abstract translation: 本发明涉及式（1）的含酰胺化合物及其盐。 在一些实施方案中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。 在另外的实施方案中，本发明涉及包含本文公开的化合物的药物组合物及其在预防和治疗Pim激酶相关病症和疾病，优选癌症中的用途。

公开(公告)号：US09346801B2

公开(公告)日：2016-05-24

申请号：US14190400

申请日：2014-02-26

Applicant: AMGEN INC.

Inventor： Andrew Tasker ,  Ryan Wurz ,  Liping H. Pettus ,  Bradley J. Herberich

IPC: C07D487/02 ,  C07D471/04

CPC classification number: C07D471/04

Abstract: The invention encompasses compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions, uses and methods for prophylaxis and treatment of cancer.

Abstract translation: 本发明包括其化合物，类似物，前药和药学上可接受的盐，药物组合物，用途和预防和治疗癌症的方法。

公开(公告)号：US20130079303A1

公开(公告)日：2013-03-28

申请号：US13681230

申请日：2012-11-19

Applicant: Amgen Inc.

Inventor： Kristin L. ANDREWS ,  Yunxin Y. Bo ,  Shon Booker ,  Victor J. Cee ,  Noel D'Angelo ,  Bradley J. Herberich ,  Fang-Tsao Hong ,  Claire I.M. Jackson ,  Brian Alan Lanman ,  Hongyu Liao ,  Longbin Liu ,  Nobuko Nishimura ,  Mark H. Norman ,  Liping H. Pettus ,  Anthony B. Reed ,  Adrian Leonard Smith ,  Seifu Tadesse ,  Nuria A. Tamayo ,  Bin Wu ,  Ryan Wurz ,  Kevin C. Yang

IPC: C07D473/00 ,  C07D417/14 ,  C07D405/14 ,  C07D413/14 ,  C07D401/14

CPC classification number: C07D473/00 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

Abstract translation: 本发明涉及式I化合物或其药学上可接受的盐; 使用该化合物治疗疾病或病症如癌症的方法; 和含有这些化合物的药物组合物，其中变量如本文所定义。