公开(公告)号：US10947223B2

公开(公告)日：2021-03-16

申请号：US16466211

申请日：2017-12-13

申请人： AMGEN INC.

发明人： Jennifer R. Allen ,  Matthew P. Bourbeau ,  Ning Chen ,  Michael J. Frohn ,  Paul E. Harrington ,  Qingyian Liu ,  Corey Reeves

IPC分类号： A61K31/535 ,  A61K31/536 ,  A61K31/537 ,  C07D265/08 ,  C07D265/12 ,  C07D265/30 ,  C07D413/10 ,  A61P25/28 ,  C07D413/14

摘要： 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: (insert Formula I structure) wherein variables W, X, Y, 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 beta amyloid (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：US10889581B2

公开(公告)日：2021-01-12

申请号：US16466199

申请日：2017-12-13

申请人： AMGEN INC.

发明人： 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分类号： C07D471/14 ,  C07D417/14 ,  C07D417/10

摘要： 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：US10246429B2

公开(公告)日：2019-04-02

申请号：US15749895

申请日：2016-08-04

申请人： AMGEN INC.

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

摘要： 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：US11512097B2

公开(公告)日：2022-11-29

申请号：US17103389

申请日：2020-11-24

申请人： Amgen Inc.

发明人： Jennifer R. Allen ,  Michela Beltrani ,  Matthew P. Bourbeau ,  Teodora P. Damyanova ,  Iain Lingard ,  Ana E. Minatti ,  Paolo Vincetti

IPC分类号： C07D513/04 ,  A61P3/04 ,  C07D487/04 ,  C07D498/04

摘要： The present disclosure provides compounds useful for the inhibition of Delta-5 Desaturase (“D5D”). The compounds have a general Formula I 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：US11021493B2

公开(公告)日：2021-06-01

申请号：US16466207

申请日：2017-12-13

申请人： AMGEN INC.

发明人： 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分类号： C07D513/08 ,  A61P25/28 ,  C07D417/10

摘要： 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：US10889579B2

公开(公告)日：2021-01-12

申请号：US16466209

申请日：2017-12-13

申请人： AMGEN INC.

发明人： Matthew P. Bourbeau ,  Paul E. Harrington ,  Qingyian Liu

IPC分类号： C07D417/10 ,  A61P25/28

摘要： 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 R1, R1′, R2, R2′, R3, R4, R5, R6, R7, and b 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：US11548903B2

公开(公告)日：2023-01-10

申请号：US16466202

申请日：2017-12-13

申请人： AMGEN INC.

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

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

摘要： 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

申请人： AMGEN INC.

发明人： 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分类号： C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10 ,  C07D417/04 ,  C07D279/08

CPC分类号： C07D417/12 ,  C07D279/08 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10

摘要： 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.

摘要翻译： 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。