公开(公告)号：US20210171529A1

公开(公告)日：2021-06-10

申请号：US17103350

申请日：2020-11-24

Applicant: Amgen Inc.

Inventor： Jennifer R. ALLEN ,  Albert AMEGADZIE ,  Matthew P. BOURBEAU ,  Ning CHEN ,  Clifford GOODMAN ,  Giulia LATTANZI ,  Iain LINGARD ,  Qingyian LIU ,  Jonathan D. LOW ,  Vu Van MA ,  Ana E. MINATTI ,  Alfonso POZZAN ,  Corey REEVES ,  Aaron C. SIEGMUND ,  Sabrina TASSINI ,  Federica TONELLI ,  Mary WALTON

IPC: C07D487/04 ,  A61P3/04 ,  C07D471/04 ,  C07D498/04

Abstract: The present disclosure provides compounds useful for the inhibition of Delta-5 Desaturase (“D5D”). The compounds have a general Formula 1: 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, a metabolic or cardiovascular disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula I.

公开(公告)号：US20160176874A1

公开(公告)日：2016-06-23

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: C07D471/04 ,  C07D403/14 ,  C07D401/14

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：US20150038497A1

公开(公告)日：2015-02-05

申请号：US14445498

申请日：2014-07-29

Applicant: AMGEN INC.

Inventor： Richard T. LEWIS ,  Jennifer R. ALLEN ,  James BROWN ,  Angel GUZMAN-PEREZ ,  Zihao HUA ,  Ted JUDD ,  Qingyian LIU ,  Philip R. OLIVIERI ,  Karina ROMERO ,  Laurie SCHENKEL ,  John STELLWAGEN ,  Ryan WHITE

IPC: C07D513/06

CPC classification number: C07D513/08 ,  C07D513/06 ,  C07D519/00

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, R1, R2, R3, R7 and n 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 Formula II and sub-formula embodiments thereof, compounds of Formula III, intermediates and processes and methods useful for the preparation of compounds of Formulas I-III, and sub-Formulas thereof.

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的变量A4，A5，A6，A8，R1，R2，R3，R7和n独立地在本文中定义。 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化合物及其次级实施方案，式III化合物，可用于制备式I-III化合物的中间体和方法和方法及其分式。

公开(公告)号：US20140249104A1

公开(公告)日：2014-09-04

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 ,  C07F7/08 ,  C07D513/04 ,  C07D413/12 ,  C07D471/04

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。 本发明进一步提供式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：US20240101570A1

公开(公告)日：2024-03-28

申请号：US18255575

申请日：2021-11-22

Applicant: AMGEN INC.

Inventor： Albert AMEGADZIE ,  Diane Jennifer BEYLKIN ,  Shon BOOKER ,  Matthew Paul BOURBEAU ,  John R. BUTLER ,  Sanne Ormholt Schroder GLAD ,  Todd J. KOHN ,  Brian Alan LANMAN ,  Kexue LI ,  Qingyian LIU ,  Patricia LOPEZ ,  Francesco MANONI ,  Primali Vasundera NAVARATNE ,  Liping H. PETTUS ,  Rene RAHIMOFF ,  Nuria A. TAMAYO ,  Mikkel VESTERGAARD ,  Hui-Ling WANG ,  Nicholas Anthony WEIRES

IPC: C07D491/048 ,  A61K35/00 ,  C07D401/12 ,  C07D401/14 ,  C07D471/04 ,  C07D471/14 ,  C07D487/04 ,  C07D491/147 ,  C07D495/04 ,  C07D498/04 ,  C07D519/00

CPC classification number: C07D491/048 ,  A61K35/00 ,  C07D401/12 ,  C07D401/14 ,  C07D471/04 ,  C07D471/14 ,  C07D487/04 ,  C07D491/147 ,  C07D495/04 ,  C07D498/04 ,  C07D519/00

Abstract: Described herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, such as cancer, metabolic and blood disorders. Compounds of Formula (I) have the following structure of Formula (I).

公开(公告)号：US20230159510A1

公开(公告)日：2023-05-25

申请号：US17799077

申请日：2021-02-11

Applicant: AMGEN INC.

Inventor： Jennifer Rebecca ALLEN ,  Albert AMEGADZIE ,  Diane Jennifer BEYLKIN ,  Shon BOOKER ,  Matthew Paul BOURBEAU ,  John R. BUTLER ,  Michael J. FROHN ,  Sanne Ormholt Schroder GLAD ,  Birgitte Weinreich HUSEMOEN ,  Matthew R. KALLER ,  Todd J. KOHN ,  Brian Alan LANMAN ,  Kexue LI ,  Qingyian LIU ,  Patricia LOPEZ ,  Vu Van MA ,  Francesco MANONI ,  Jose MEDINA ,  Ana Elena MINATTI ,  Jorge PEIRO CADAHIA ,  Liping PETTUS ,  Alexander J. PICKRELL ,  Ian SARVARY ,  Nuria A. TAMAYO ,  Mikkel VESTERGAARD

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

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

Abstract: Described herein are compounds of Formula I and pharmaceutically acceptable salt thereof, stereoisomers, tautomers as well as 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: (I)

公开(公告)号：US20200231601A1

公开(公告)日：2020-07-23

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 ,  C07D417/10 ,  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: 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：US20180222876A1

公开(公告)日：2018-08-09

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

CPC classification number: C07D279/08 ,  A61P25/00 ,  A61P25/16 ,  A61P25/28 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D491/056 ,  C07D491/08 ,  C07D491/107 ,  C07D498/10 ,  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, 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：US20160102075A1

公开(公告)日：2016-04-14

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 ,  C07D409/14 ,  C07D403/14 ,  C07D491/107 ,  C07D487/10 ,  C07C53/18 ,  C07D405/14 ,  C07D413/14 ,  C07D487/04 ,  C07D491/08 ,  C07D487/08 ,  C07D471/04 ,  C07D491/056 ,  C07D513/04 ,  C07D417/14

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：US20140107109A1

公开(公告)日：2014-04-17

申请号：US14051339

申请日：2013-12-18

Applicant: Amgen Inc.

Inventor： Richard T. LEWIS ,  Jennifer R. ALLEN ,  Yuan CHENG ,  Deborah CHOQUETTE ,  Oleg EPSTEIN ,  Angel GUZMAN-PEREZ ,  Paul E. HARRINGTON ,  Zihao HUA ,  Randall W. HUNGATE ,  Jason Brooks HUMAN ,  Ted JUDD ,  Qingyian LIU ,  Patricia LOPEZ ,  Ana Elena MINATTI ,  Philip OLIVIERI ,  Karina ROMERO ,  Shannon RUMFELT ,  Robert M. RZASA ,  Laurie SCHENKEL ,  John STELLWAGEN ,  Ryan WHITE ,  Qiufen XUE ,  Xiao ZHENG ,  Wenge ZHONG

IPC: C07D513/04 ,  C07D513/10 ,  C07D279/12 ,  C07D498/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D279/14 ,  C07D417/04

CPC classification number: C07D279/12 ,  C07D213/79 ,  C07D239/74 ,  C07D241/44 ,  C07D279/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  C07D513/10 ,  C07D519/00

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, R1, R2, R3, R7 and n 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 Formula II and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.

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的变量A4，A5，A6，A8，R1，R2，R3，R7和n独立地在本文中定义。 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化合物及其次级实施方案，可用于制备式I-II化合物的中间体和方法和方法。