公开(公告)号：US20160280703A1

公开(公告)日：2016-09-29

申请号：US14579733

申请日：2014-12-22

Applicant: Amgen Inc.

Inventor： Jennifer R. Allen ,  Michael J. Frohn ,  Paul E. Harrington ,  Essa Hu Harrington ,  Alexander J. Pickrell

IPC: C07D417/14 ,  C07D413/14 ,  C07D471/04 ,  C07D417/12 ,  C07D487/04 ,  C07D405/14 ,  C07D401/14

CPC classification number: C07D417/14 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04

Abstract: Heteroaryloxycarbocyclyl compounds, 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, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 杂芳氧基碳环化合物和含有它们的组合物，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，亨廷顿舞蹈病，双相情感障碍，强迫症等。

公开(公告)号：US09303028B2

公开(公告)日：2016-04-05

申请号：US14170146

申请日：2014-01-31

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Jian J. Chen ,  Michael J. Frohn ,  Matthew R. Kaller ,  Qingyian Liu ,  Thomas T. Nguyen ,  Alexander J. Pickrell ,  Wenyuan Qian ,  Robert M. Rzasa ,  Wenge Zhong

IPC: A61K31/497 ,  A61K31/517 ,  C07D401/14 ,  C07D403/14 ,  C07D471/04 ,  A61K45/06

CPC classification number: C07D471/04 ,  A61K31/497 ,  A61K31/517 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14

Abstract: Azetidine and piperidine compounds of formula (I): as defined in the specification, compositions containing them, and processes for preparing such compounds and intermediates thereof. Provided herein also are methods of treating cognitive disorders or diseases treatable by inhibition of PDE10, such as Huntington's Disease, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 式（I）的氮杂环丁烷和哌啶化合物：如说明书中所定义，含有它们的组合物，以及制备这些化合物的方法及其中间体。 本文还提供治疗认知障碍或通过抑制PDE10可治疗的疾病的方法，例如亨廷顿舞蹈病，精神分裂症，双相障碍，强迫症等。

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：US09718803B2

公开(公告)日：2017-08-01

申请号：US14973491

申请日：2015-12-17

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Jian J. Chen ,  Michael J. Frohn ,  Essa Hu Harrington ,  Qingyian Liu ,  Alexander J. Pickrell ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Wenge Zhong

IPC: C07D401/14 ,  A61K31/497 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D491/08 ,  C07D487/08 ,  C07D487/10 ,  C07D491/107 ,  C07C53/18 ,  C07D491/056 ,  C07D513/04

CPC classification number: C07D401/14 ,  C07C53/18 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/056 ,  C07D491/08 ,  C07D491/107 ,  C07D513/04

Abstract: Unsaturated nitrogen heterocyclic compounds of formula (I): as defined in the specification, 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, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

公开(公告)号：US09611261B2

公开(公告)日：2017-04-04

申请号：US14932787

申请日：2015-11-04

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 ,  C07D413/14 ,  C07D413/12 ,  C07D417/14 ,  C07D417/12 ,  C07D413/10 ,  C07D491/048 ,  C07D413/04

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.

公开(公告)号：US09493459B2

公开(公告)日：2016-11-15

申请号：US15058023

申请日：2016-03-01

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Jian J. Chen ,  Michael J. Frohn ,  Matthew R. Kaller ,  Qingyian Liu ,  Thomas T. Nguyen ,  Alexander J. Pickrell ,  Wenyuan Qian ,  Robert M. Rzasa ,  Wenge Zhong

IPC: C07D401/04 ,  C07D403/04 ,  C07D471/04 ,  C07D401/14 ,  A61K31/497 ,  A61K45/06 ,  A61K31/517 ,  C07D403/14

CPC classification number: C07D471/04 ,  A61K31/497 ,  A61K31/517 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14

Abstract: Azetidine and piperidine compounds of formula (I): as defined in the specification, compositions containing them, and processes for preparing such compounds and intermediates thereof. Provided herein also are methods of treating cognitive disorders or diseases treatable by inhibition of PDE10, such as Huntington's Disease, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

公开(公告)号：US20140213572A1

公开(公告)日：2014-07-31

申请号：US14242432

申请日：2014-04-01

Applicant: AMGEN INC.

Inventor： Jennifer R. Allen ,  Jian J. Chen ,  Michael J. Frohn ,  Essa Hu Harrington ,  Qingyian Liu ,  Alexander J. Pickrell ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Wenge Zhong

IPC: C07D403/14 ,  C07D417/14 ,  C07D409/14 ,  C07D413/14 ,  C07D487/08 ,  C07D487/10 ,  C07D405/14 ,  C07D487/04 ,  C07D491/08 ,  C07D401/14 ,  C07D491/107

CPC classification number: C07D401/14 ,  C07C53/18 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/056 ,  C07D491/08 ,  C07D491/107 ,  C07D513/04

Abstract: Unsaturated nitrogen heterocyclic compounds of formula (I): as defined in the specification, 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, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 式（I）的不饱和氮杂环化合物：如说明书中所定义，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，亨廷顿舞蹈病，非胰岛素依赖性糖尿病，精神分裂症，双相障碍，强迫症等。

公开(公告)号：US08759532B2

公开(公告)日：2014-06-24

申请号：US13676826

申请日：2012-11-14

Applicant: AMGEN Inc.

Inventor： Jennifer R. Allen ,  Kaustav Biswas ,  Frank Chavez, Jr. ,  Ning Chen ,  Frenel Fils De Morin ,  James R. Falsey ,  Michael J. Frohn ,  Paul E. Harrington ,  Daniel B. Home ,  Essa Hu Harrington ,  Matthew R. Kaller ,  Roxanne K. Kunz ,  Holger Monenschein ,  Thomas T. Nguyen ,  Alexander J. Pickrell ,  Andreas Reichelt ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Kelvin Sham ,  Guomin Yao

IPC: C07D239/02 ,  A61K31/397

CPC classification number: C07D413/14 ,  C07D401/12 ,  C07D401/14 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00

Abstract: Pyridine and pyrimidine compounds, 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, and the like.

Abstract translation: 吡啶和嘧啶化合物，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，非胰岛素依赖型糖尿病，精神分裂症，双相情感障碍，强迫症等。

公开(公告)号：US11090304B2

公开(公告)日：2021-08-17

申请号：US16402538

申请日：2019-05-03

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

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：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。