公开(公告)号：US20170267673A1

公开(公告)日：2017-09-21

申请号：US15354877

申请日：2016-11-17

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 R. 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 ,  C07D279/08 ,  C07D417/04 ,  C07D513/10

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.

公开(公告)号：US20160046618A1

公开(公告)日：2016-02-18

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 ,  C07D471/04 ,  C07D513/10 ,  C07D417/14

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：US20150252059A1

公开(公告)日：2015-09-10

申请号：US14717339

申请日：2015-05-20

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: C07D513/08 ,  C07D519/00

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.

公开(公告)号：US20140213581A1

公开(公告)日：2014-07-31

申请号：US14166012

申请日：2014-01-28

Applicant: AMGEN INC.

Inventor： Ryan WHITE ,  Jennifer R. ALLEN ,  Oleg EPSTEIN ,  Fang-Tsao HONG ,  Zihao HUA ,  Jason Brooks HUMAN ,  Patricia LOPEZ ,  Philip R. OLIVIERI ,  Karina ROMERO ,  Laurie SCHENKEL ,  John STELLWAGEN ,  Nuria A. TAMAYO ,  Xiao Mei ZHENG

IPC: C07D513/04 ,  C07D513/14

CPC classification number: C07D513/04 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/10 ,  C07D513/14 ,  C07D513/20 ,  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 A5, A6, A8, R1, R2, R3, R7, X, Y, n and o 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A5，A6，A8，R1，R2，R3，R7，X，Y，n和o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。 本发明进一步提供式II化合物及其次式实施方案，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：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：US20200231585A1

公开(公告)日：2020-07-23

申请号：US16466199

申请日：2017-12-13

Applicant: AMGEN INC.

Inventor： Jennifer R. ALLEN ,  Albert AMEGADZIE ,  Matthew P. BOURBEAU ,  Jian J. CHEN ,  Michael J. FROHN ,  Paul E. HARRINGTON ,  Jonathan D. LOW ,  Vu V. MA ,  Thomas T. NGUYEN ,  Alexander PICKRELL ,  Corey REEVES

IPC: C07D417/14 ,  C07D417/10

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) wherein variables A, R1, R2, R2′, R3, R4, and R5 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：US20160280695A1

公开(公告)日：2016-09-29

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: C07D413/12

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: 其中式I的Ra，Rb，R1，R2，R3和R7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：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。