公开(公告)号：EP1794135A1

公开(公告)日：2007-06-13

申请号：EP05802134.6

申请日：2005-09-27

申请人： Amgen Inc.

发明人： ANDERSEN, Denise, Lyn ,  CHANG, Catherine, H. ,  FALSEY, James, R. ,  FROHN, Michael, J. ,  HONG, Fang-Tsao ,  LIAO, Hongyu ,  LIU, Longbin ,  LOPEZ, Patricia ,  RETZ, Daniel, Martin ,  RISHTON, Gilbert, M. ,  RZASA, Robert, M. ,  SIEGMUND, Aaron, C. ,  TADESSE, Seifu ,  TAMAYO, Nuria ,  TEGLEY, Christopher, M.

IPC分类号： C07D239/48 ,  A61K31/506 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14

CPC分类号： C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14

摘要： The present invention relates to pyridines, pyrimidines and derivatives thereof, (I) or a pharmaceutically acceptable salts thereof, wherein X1 is N or CR3; X2 is N or CR4; or -X1=X2- is -C(=O)-N(Ra)- or -N(Ra)-C(=O)-; X3 is N or CR4; X4 is N or CR4; X5 is N or CR6; X6 is N or CR6; wherein only 1, 2 or 3 of X1, X2, X3 and X4 are N; R1 is a saturated partially saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, O and S, wherein the ring is substituted by 0, 1, 2 or 3 substituents. Also included is a method of treatment of inflammation, rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveititis, acute or chronic myelogenous leukemia, pancreatic ß cell destruction, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, adult respiratory distress syndrome (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases, graft vs. host reaction, Alzheimer's disease, stroke, myocardial infarction, ischemia reperfusion injury, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever, myalgias due to HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, the herpes viruses or herpes zoster infection in a mammal comprising administering an effective amount a compound as described above.

公开(公告)号：EP2077998B1

公开(公告)日：2011-03-09

申请号：EP07837737.1

申请日：2007-09-04

申请人： Amgen Inc.

发明人： TASKER, Andrew ,  ZHANG, Dawei ,  PETTUS, Liping, H. ,  RZASA, Robert, M. ,  SHAM, Kelvin, K.C. ,  XU, Shimin ,  CHAKRABARTI, Partha, Pratim

IPC分类号： C07D237/30 ,  C07D237/34 ,  C07D403/12 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04 ,  A61K31/501 ,  A61P29/00

CPC分类号： C07D403/12 ,  C07D237/30 ,  C07D237/34 ,  C07D403/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04

摘要： The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A1, A2, B, R1, R2, R3 and R4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

公开(公告)号：EP2086973B1

公开(公告)日：2012-01-25

申请号：EP07839356.8

申请日：2007-10-05

申请人： Amgen Inc.,

发明人： ZHANG, Dawei ,  TASKER, Andrew ,  SHAM, Kelvin, K.C. ,  CHAKRABARTI, Partha, Pratim ,  FALSEY, Richard, James ,  HERBERICH, Bradley, J. ,  PETTUS, Liping, H. ,  RZASA, Robert, M.

IPC分类号： C07D471/04

CPC分类号： C07D471/04

摘要： The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have general Formula (I), wherein A, B, R1, R2, R3 and R4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula (I), uses of such compounds and compositions for treatment of P38 map kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula (I).

公开(公告)号：EP2300427A1

公开(公告)日：2011-03-30

申请号：EP09743390.8

申请日：2009-05-04

申请人： AMGEN INC.

发明人： BISWAS, Kaustav ,  CHEN, Jian, J. ,  FALSEY, James, Richard ,  GORE, Vijay, Keshav ,  LIU, Qingyian ,  MA, Vu, Van ,  MERCEDE, Stephanie, J. ,  RZASA, Robert, M. ,  TEGLEY, Christopher, M. ,  ZHU, Jiawang

IPC分类号： C07D213/40 ,  C07D213/61 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  A61K31/44 ,  A61K31/4709 ,  A61P25/28

CPC分类号： C07D213/40 ,  C07D213/61 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： The present invention provides compounds Formula (I) that are gamma secretase modulators and are therefore useful for the treatment of diseases treatable by modulation of gamma secretase such as Alzheimer's disease. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

公开(公告)号：EP2086973A2

公开(公告)日：2009-08-12

申请号：EP07839356.8

申请日：2007-10-05

申请人： Amgen Inc.,

发明人： ZHANG, Dawei ,  TASKER, Andrew ,  SHAM, Kelvin, K.C. ,  CHAKRABARTI, Partha, Pratim ,  FALSEY, Richard, James ,  HERBERICH, Bradley, J. ,  PETTUS, Liping, H. ,  RZASA, Robert, M.

IPC分类号： C07D471/04

CPC分类号： C07D471/04

摘要： The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have general Formula (I), wherein A, B, R1, R2, R3 and R4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula (I), uses of such compounds and compositions for treatment of P38 map kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula (I).

公开(公告)号：EP2077998A1

公开(公告)日：2009-07-15

申请号：EP07837737.1

申请日：2007-09-04

申请人： Amgen Inc. ,  Tasker, Andrew ,  Zhang, Dawei

发明人： TASKER, Andrew ,  ZHANG, Dawei ,  PETTUS, Liping, H. ,  RZASA, Robert, M. ,  SHAM, Kelvin, K.C. ,  XU, Shimin ,  CHAKRABARTI, Partha, Pratim

IPC分类号： C07D237/30 ,  C07D237/34 ,  C07D403/12 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04 ,  A61K31/501 ,  A61P29/00

CPC分类号： C07D403/12 ,  C07D237/30 ,  C07D237/34 ,  C07D403/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04

摘要： The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A1, A2, B, R1, R2, R3 and R4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

公开(公告)号：EP2964644B1

公开(公告)日：2018-12-26

申请号：EP14717004.7

申请日：2014-03-06

申请人： AMGEN, INC.

发明人： MINATTI, Ana Elena ,  LOW, Jonathan, D. ,  ALLEN, Jennifer, R. ,  AMEGADZIE, Albert ,  BROWN, James ,  FROHN, Michael, J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul, E. ,  LOPEZ, Patricia ,  MA, Vu Van ,  NISHIMURA, Nobuko ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert, M. ,  SHAM, Kelvin ,  SMITH, Adrian, L. ,  WHITE, Ryan ,  XUE, Qiufen

IPC分类号： C07D413/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D265/12 ,  C07D491/048 ,  A61P25/00 ,  A61K31/536

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：EP2964644A1

公开(公告)日：2016-01-13

申请号：EP14717004.7

申请日：2014-03-06

申请人： Amgen Inc.

发明人： MINATTI, Ana Elena ,  LOW, Jonathan, D. ,  ALLEN, Jennifer, R. ,  AMEGADZIE, Albert ,  BROWN, James ,  FROHN, Michael, J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul, E. ,  LOPEZ, Patricia ,  MA, Vu Van ,  NISHIMURA, Nobuko ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert, M. ,  SHAM, Kelvin ,  SMITH, Adrian, L. ,  WHITE, Ryan ,  XUE, Qiufen

IPC分类号： C07D413/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D265/12 ,  C07D491/048 ,  A61P25/00 ,  A61K31/536

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.

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，以及由BACE的生物活性产生的化合物和组合物用于治疗与A-β斑块形成和沉积相关的病症和/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。