公开(公告)号：US20140005198A1

公开(公告)日：2014-01-02

申请号：US14012861

申请日：2013-08-28

Applicant: AMGEN INC.

Inventor： Adrian L. SMITH ,  Elizabeth M. DOHERTY ,  Qi HUANG ,  Gang LIU

IPC: C07D487/04 ,  C07D473/00

CPC classification number: C07D487/04 ,  C07D473/00

Abstract: The present invention comprises a new class of compounds capable of modulating the activity of Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have a general Formula I wherein each of A1, A2, A3, A4, A5, A6, A7, A8, A9, bond B, X, rings Z1 and Z2, R1 and R3 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

Abstract translation: 本发明包括能够调节Raf激酶活性的新一类化合物，因此可用于治疗Raf激酶介导的疾病，包括黑素瘤，肿瘤和其它癌症相关病症。 该化合物具有通式I，其中A1，A2，A3，A4，A5，A6，A7，A8，A9，键B，X，环Z1和Z2，R1和R3各自定义。 本发明还包括药物组合物，用于治疗Raf激酶介导的疾病的方法，以及可用于制备本发明化合物的中间体和方法。

公开(公告)号：US20150329538A1

公开(公告)日：2015-11-19

申请号：US14380918

申请日：2013-02-27

Applicant: AMGEN INC.

Inventor： Victor CEE ,  Frank CHAVEZ, JR. ,  Jian J. CHEN ,  Essa Hu HARRINGTON ,  Bradley HERBERICH ,  Claire L.M. JACKSON ,  Brian A. LANMAN ,  Thomas T. NGUYEN ,  Mark H. NORMAN ,  Liping H. PETTUS ,  Anthony B. REED ,  Adrian L. SMITH ,  Nuria A. TAMAYO ,  Andrew TASKER ,  Hui-Ling WANG ,  Bin WU ,  Ryan WURZ

IPC: C07D471/04 ,  C07D401/04 ,  C07D487/04

CPC classification number: C07D471/04 ,  C07D401/04 ,  C07D487/04

Abstract: The invention relates to amide-containing compounds of formula (1), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

Abstract translation: 本发明涉及式（1）的含酰胺化合物及其盐。 在一些实施方案中，本发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。 在另外的实施方案中，本发明涉及包含本文公开的化合物的药物组合物及其在预防和治疗Pim激酶相关病症和疾病，优选癌症中的用途。

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：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。