公开(公告)号：US11905281B2

公开(公告)日：2024-02-20

申请号：US17031607

申请日：2020-09-24

申请人： Amgen Inc.

发明人： Brian Alan Lanman ,  Jian Chen ,  Anthony B. Reed ,  Victor J. Cee ,  Longbin Liu ,  David John Kopecky ,  Patricia Lopez ,  Ryan Paul Wurz ,  Thomas T. Nguyen ,  Shon Booker ,  Nobuko Nishimura ,  Youngsook Shin ,  Nuria A. Tamayo ,  John Gordon Allen ,  Jennifer Rebecca Allen

IPC分类号： C07D471/04 ,  C07D213/82 ,  C07D417/04 ,  A61K38/07 ,  C07D487/08 ,  C07D417/12 ,  C07D513/04 ,  C07D487/10 ,  C07D487/04 ,  C07D401/04 ,  C07D239/80 ,  C07D401/14 ,  C07D237/34 ,  C07D403/04 ,  A61K31/496 ,  A61K31/416 ,  A61K31/55 ,  A61K31/454 ,  A61K31/519 ,  A61K31/502 ,  A61K31/517 ,  A61K31/5025 ,  A61P35/00 ,  A61K31/7068 ,  C07D275/04 ,  C07D475/00

CPC分类号： C07D417/04 ,  A61K31/416 ,  A61K31/454 ,  A61K31/496 ,  A61K31/502 ,  A61K31/5025 ,  A61K31/517 ,  A61K31/519 ,  A61K31/55 ,  A61K31/7068 ,  A61K38/07 ,  A61P35/00 ,  C07D237/34 ,  C07D239/80 ,  C07D275/04 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D417/12 ,  C07D471/04 ,  C07D475/00 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D513/04

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：US11845760B2

公开(公告)日：2023-12-19

申请号：US17552016

申请日：2021-12-15

申请人： AMGEN INC.

发明人： Shon Booker ,  Matthew Paul Bourbeau ,  John R. Butler ,  Sanne Ormholt Schroder Glad ,  Brian Alan Lanman ,  Patricia Lopez ,  Francesco Manoni ,  Liping H. Pettus ,  Ian Sarvary ,  Nuria A. Tamayo ,  Mikkel Vestergaard ,  Nicholas Anthony Weires

IPC分类号： C07D471/04 ,  C07D471/14 ,  C07D491/04 ,  C07D491/14 ,  C07D495/04 ,  A61K31/4355 ,  A61K31/436 ,  A61K31/4365 ,  A61K31/437 ,  A61K31/4375 ,  A61P35/00 ,  C07D491/06 ,  C07D471/06 ,  C07D471/16 ,  C07D491/16

CPC分类号： C07D491/06 ,  A61P35/00 ,  C07D471/06 ,  C07D471/16 ,  C07D491/16

摘要： Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the 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:

公开(公告)号：US11827635B2

公开(公告)日：2023-11-28

申请号：US17553598

申请日：2021-12-16

申请人： AMGEN INC.

发明人： Mary Chaves ,  Patricia Lopez ,  Prashant Agarwal ,  Albert Amegadzie ,  Stephanie Azali ,  Roman Shimanovich ,  Ron C. Kelly ,  Darren Leonard Reid

IPC分类号： C07D471/04

CPC分类号： C07D471/04 ,  C07B2200/13

摘要： The present disclosure provides crystalline and amorphous forms of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, including several anhydrous, hydrate and solvate forms, and solid state forms thereof, pharmaceutical compositions, and methods of treating a disease mediated by KRAS G12C inhibition.

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：US11236091B2

公开(公告)日：2022-02-01

申请号：US16878824

申请日：2020-05-20

申请人： AMGEN INC.

发明人： Mary Chaves ,  Patricia Lopez ,  Prashant Agarwal ,  Albert Amegadzie ,  Stephanie Azali ,  Roman Shimanovich ,  Ron C. Kelly ,  Darren Leonard Reid

IPC分类号： C07D471/04

摘要： The present disclosure provides crystalline and amorphous forms of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, including several anhydrous, hydrate and solvate forms, and solid state forms thereof, pharmaceutical compositions, and methods of treating a disease mediated by KRAS G12C inhibition.

公开(公告)号：US11096939B2

公开(公告)日：2021-08-24

申请号：US16428163

申请日：2019-05-31

申请人： Amgen Inc.

发明人： Shon Booker ,  John Gordon Allen ,  Brian Alan Lanman ,  Ryan Paul Wurz ,  Ning Chen ,  Victor J. Cee ,  Patricia Lopez ,  Aaron C. Siegmund ,  Michael D. Bartberger

IPC分类号： C07D471/04 ,  A61K31/497 ,  C07K16/28

摘要： Provided herein are KRAS G12C inhibitors, such as 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：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：US09309263B2

公开(公告)日：2016-04-12

申请号：US14166012

申请日：2014-01-28

申请人： AMGEN INC.

发明人： 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分类号： C07D417/10 ,  C07D417/14 ,  C07D513/04 ,  C07D513/14 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/10 ,  C07D513/20 ,  C07D519/00

CPC分类号： C07D513/04 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/10 ,  C07D513/14 ,  C07D513/20 ,  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 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.

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：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。