公开(公告)号：US20240327384A1

公开(公告)日：2024-10-03

申请号：US18580564

申请日：2022-07-21

Applicant: Amgen Inc.

Inventor： Tian WU ,  Prashant AGARWAL ,  Andreas R. ROTHELI ,  Hyunsoo PARK ,  Michael J. FROHN

IPC: C07D401/14 ,  A61K31/506 ,  C07C15/06 ,  C07C31/02 ,  C07C31/04 ,  C07C31/08 ,  C07C43/04 ,  C07C43/18 ,  C07C49/08 ,  C07C55/02 ,  C07C55/22 ,  C07C69/003 ,  C07C233/05 ,  C07C255/03 ,  C07C275/06 ,  C07C309/04 ,  C07C309/65 ,  C07C309/73 ,  C07D211/90 ,  C07D275/06 ,  C07D307/06 ,  C07D319/12 ,  C07D487/04

CPC classification number: C07D401/14 ,  A61K31/506 ,  C07C15/06 ,  C07C31/02 ,  C07C31/04 ,  C07C31/08 ,  C07C43/046 ,  C07C43/18 ,  C07C49/08 ,  C07C55/02 ,  C07C55/22 ,  C07C69/003 ,  C07C233/05 ,  C07C255/03 ,  C07C275/06 ,  C07C309/04 ,  C07C309/65 ,  C07C309/73 ,  C07D211/90 ,  C07D275/06 ,  C07D307/06 ,  C07D319/12 ,  C07D487/04 ,  C07B2200/13 ,  C07C2601/08

Abstract: Disclosed herein is a salt, a crystalline anhydrous form, a hydrate, a solvate, or a co-crystal of a free base compound 2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-[(2-hydroxyethanesulfonyl)amino]benzamide (Compound A); method of preparation, pharmaceutical compositions, and method of treating a disease mediated by a motor protein kinesin family member 18A (KIF18A) inhibition, wherein said disease is a neoplastic disease, including a cancer or a tumor.

公开(公告)号：US20240050430A1

公开(公告)日：2024-02-15

申请号：US18213464

申请日：2023-06-23

Applicant: Amgen Inc.

Inventor： 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: A61K31/517 ,  A61P35/00 ,  A61K31/4985 ,  A61K39/395 ,  C07D403/04 ,  C07D471/04

CPC classification number: A61K31/517 ,  A61P35/00 ,  C07D471/04 ,  A61K39/39558 ,  C07D403/04 ,  A61K31/4985

Abstract: 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：US20220372018A1

公开(公告)日：2022-11-24

申请号：US17632334

申请日：2020-08-03

Applicant: AMGEN INC.

Inventor： Nuria A. TAMAYO ,  Abhisek BANERJEE ,  Jian Jeffrey CHEN ,  Matthew Richard KALLER ,  Thomas T. NGUYEN ,  Nobuko NISHIMURA ,  Qiufen May XUE ,  John Gordon ALLEN ,  Michael J. FROHN

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

Abstract: Amide 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：US20240317715A1

公开(公告)日：2024-09-26

申请号：US18680558

申请日：2024-05-31

Applicant: AMGEN INC.

Inventor： 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: C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14 ,  C07D419/14 ,  C07D491/107

CPC classification number: C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14 ,  C07D419/14 ,  C07D491/107

Abstract: 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：US20200239441A1

公开(公告)日：2020-07-30

申请号：US16724119

申请日：2019-12-20

Applicant: AMGEN INC.

Inventor： 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: C07D401/14 ,  C07D401/12 ,  C07D405/14 ,  C07D413/14 ,  C07D419/14 ,  C07D491/107

Abstract: 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：US20150252011A1

公开(公告)日：2015-09-10

申请号：US14691715

申请日：2015-04-21

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: C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D413/12 ,  C07D471/04

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: 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中的每个R a，R b，R 1，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：US20140275058A1

公开(公告)日：2014-09-18

申请号：US14199844

申请日：2014-03-06

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: C07D471/04 ,  C07D265/12 ,  C07D417/12 ,  C07D417/14 ,  C07D413/12 ,  C07D413/14

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: 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中的每个R a，R b，R 1，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：US20200207747A1

公开(公告)日：2020-07-02

申请号：US16466211

申请日：2017-12-13

Applicant: AMGEN INC.

Inventor： Jennifer R. ALLEN ,  Matthew P. BOURBEAU ,  Ning CHEN ,  Michael J. FROHN ,  Paul E. HARRINGTON ,  Qingyian LIU ,  Corey REEVES

IPC: C07D413/10 ,  C07D413/14 ,  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: (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：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。