公开(公告)号：US09777019B2

公开(公告)日：2017-10-03

申请号：US15041835

申请日：2016-02-11

申请人： AMGEN INC.

发明人： Ryan White ,  Yuan Cheng ,  Ana Elena Minatti ,  Bryant Yang ,  Xiao Mei Zheng ,  Patricia Lopez ,  Jason B. Human ,  Oleg Epstein ,  Ted Judd ,  Kelvin Sham ,  Qiufen Xue

IPC分类号： A61K31/537 ,  A61K31/547 ,  C07D498/10 ,  C07D513/10 ,  C07D498/20 ,  C07D513/20

CPC分类号： C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A3, A4, A5, A6, L, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

公开(公告)号：US09012446B2

公开(公告)日：2015-04-21

申请号：US13929483

申请日：2013-06-27

申请人： Amgen Inc.

发明人： Jian Chen ,  Wenge Zhong ,  Patricia Lopez ,  Ryan White ,  Matthew Weiss ,  Ted Judd ,  Timothy Powers ,  Yuan Cheng ,  Thomas Dineen ,  Jonathan D. Low ,  Isaac E. Marx ,  Ana Elena Minatti

IPC分类号： C07D498/10 ,  C07D498/20 ,  C07D513/20 ,  C07D513/10

CPC分类号： C07D513/10 ,  C07D498/10 ,  C07D498/20 ,  C07D513/20

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中式I中的A1，A2，A3，A4，A5，A6，R2，R7，X，Y和Z如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

公开(公告)号：US20180289720A1

公开(公告)日：2018-10-11

申请号：US15938001

申请日：2018-03-28

申请人： AMGEN INC.

发明人： Paul E. Harrington ,  Kate Ashton ,  Sean P. Brown ,  Matthew R. Kaller ,  Todd J. Kohn ,  Brian Alan Lanman ,  Kexue Li ,  Yunxiao Li ,  Jonathan D. Low ,  Ana Elena Minatti ,  Alexander J. Pickrell ,  Markian M. Stec ,  Joshua Taygerly

IPC分类号： A61K31/553 ,  A61P35/00

CPC分类号： A61K31/553 ,  A61P35/00 ,  A61P35/02 ,  C07D498/08

摘要： Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

公开(公告)号：US09611261B2

公开(公告)日：2017-04-04

申请号：US14932787

申请日：2015-11-04

申请人： AMGEN INC.

发明人： 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分类号： C07D471/04 ,  C07D265/12 ,  C07D413/14 ,  C07D413/12 ,  C07D417/14 ,  C07D417/12 ,  C07D413/10 ,  C07D491/048 ,  C07D413/04

CPC分类号： C07D413/12 ,  C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

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, 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：US09556135B2

公开(公告)日：2017-01-31

申请号：US14433769

申请日：2013-10-10

申请人： Amgen Inc.

发明人： 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 Mei Zheng ,  Wenge Zhong

IPC分类号： C07D279/12 ,  C07D417/04 ,  C07D471/04 ,  C07D239/74 ,  C07D495/04 ,  C07D213/79 ,  C07D241/44 ,  C07D417/12 ,  C07D417/14 ,  C07D513/04 ,  C07D498/04 ,  C07D513/10 ,  C07D279/14 ,  C07D519/00

CPC分类号： 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

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, 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.

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。 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。

公开(公告)号：US12054476B2

公开(公告)日：2024-08-06

申请号：US17551105

申请日：2021-12-14

申请人： AMGEN INC.

发明人： 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分类号： C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14 ,  C07D419/14 ,  C07D491/107

CPC分类号： C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14 ,  C07D419/14 ,  C07D491/107

摘要： 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：US11236069B2

公开(公告)日：2022-02-01

申请号：US16724119

申请日：2019-12-20

申请人： AMGEN INC.

发明人： Nuria A. Tamayo ,  Abhisek Banerjee ,  Jian Jeffrey Chen ,  Jonathan Dante Low ,  Ana Elena Minatti ,  Matthew Paul Bourbeau

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

摘要： 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：US11090304B2

公开(公告)日：2021-08-17

申请号：US16402538

申请日：2019-05-03

申请人： Amgen Inc.

发明人： 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分类号： A61K31/517 ,  A61P35/00 ,  A61K31/4985 ,  A61K39/395 ,  C07D403/04 ,  C07D471/04

摘要： 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：US10988485B2

公开(公告)日：2021-04-27

申请号：US16407889

申请日：2019-05-09

申请人： Amgen Inc.

发明人： Ana Elena Minatti ,  Jonathan Dante Low ,  Ryan Paul Wurz ,  Brian Alan Lanman ,  Victor J. Cee ,  Michael D. Bartberger ,  Margaret Chu-Moyer

IPC分类号： C07D513/04 ,  A61K45/06 ,  C07K16/28

摘要： 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

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。