公开(公告)号：WO2006060318A3

公开(公告)日：2006-06-08

申请号：PCT/US2005/042935

申请日：2005-11-29

Applicant: AMGEN INC. ,  KIM, Tae-seong ,  BELLON, Steven ,  BOOKER, Shon ,  D'ANGELO, Noel ,  DOMINGUEZ, Celia ,  FELLOWS, Ingrid ,  LEE, Matthew ,  LIU, Longbin ,  RAINBEAU, Elizabeth ,  SIEGMUND, Aaron, C. ,  TASKER, Andrew ,  XI, Ning ,  CHENG, Yuan

Inventor： KIM, Tae-seong ,  BELLON, Steven ,  BOOKER, Shon ,  D'ANGELO, Noel ,  DOMINGUEZ, Celia ,  FELLOWS, Ingrid ,  LEE, Matthew ,  LIU, Longbin ,  RAINBEAU, Elizabeth ,  SIEGMUND, Aaron, C. ,  TASKER, Andrew ,  XI, Ning ,  CHENG, Yuan

IPC: A61K31/4709 ,  C07D401/12 ,  C07D401/14 ,  A61P35/00

Abstract: Selected compounds of Formula (I) are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases such as cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. R - X - W - A - Y - R Formula (I) wherein R is X is O, S, NR2 or CR3R4 W is an substituted or unsubstituted aryl or substituted or unsubstituted 5- or 6- membered heteroaryl.

公开(公告)号：WO2017024180A1

公开(公告)日：2017-02-09

申请号：PCT/US2016/045650

申请日：2016-08-04

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer, R. ,  AMEGADZIE, Albert ,  BOURBEAU, Matthew, P. ,  BROWN, James, A. ,  CHEN, Ning ,  FROHN, Michael, J. ,  LIU, Longbin ,  LIU, Qingyian ,  PETTUS, Liping, H. ,  QIAN, Wenyuan ,  REEVES, Corey, M. ,  SIEGMUND, Aaron, C.

IPC: A61K31/5415 ,  A61P25/28 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D491/056 ,  C07D279/08

CPC classification number: C07D417/10 ,  C07D279/08 ,  C07D417/14 ,  C07D471/04 ,  C07D491/056

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 A 4 , A 5 , A 6 , A 7 , and each of R a , R b , R 1 , R 2 , R 3 , R 8 R 9 and R 10 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 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, schizophrenia and other central nervous system conditions.

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中的变量A4，A5，A6，A7以及式I的R a，R b，R 1，R 2，R 3，R 8 R 9和R 10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，以及由BACE的生物活性产生的化合物和组合物用于治疗与Aβ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。

公开(公告)号：WO2010108074A2

公开(公告)日：2010-09-23

申请号：PCT/US2010/027929

申请日：2010-03-19

Applicant: AMGEN INC. ,  BO, Yunxin, Y. ,  LIU, Longbin ,  NISHIMURA, Nobuko ,  NORMAN, Mark, H. ,  SIEGMUND, Aaron, C. ,  TAMAYO, Nuria, A. ,  YANG, Kevin

Inventor： BO, Yunxin, Y. ,  LIU, Longbin ,  NISHIMURA, Nobuko ,  NORMAN, Mark, H. ,  SIEGMUND, Aaron, C. ,  TAMAYO, Nuria, A. ,  YANG, Kevin

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: The present invention relates to compounds of Formula I, II or III or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

Abstract translation: 本发明涉及式I，II或III的化合物或其药学上可接受的盐; 使用该化合物治疗疾病或病症如癌症的方法; 和含有这些化合物的药物组合物，其中变量如本文所定义。

公开(公告)号：WO2006037117A1

公开(公告)日：2006-04-06

申请号：PCT/US2005/035134

申请日：2005-09-27

Applicant: AMGEN INC.

Inventor： ANDERSEN, Denise, Lyn ,  CHANG, Catherine, M. ,  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: C07D239/48 ,  A61K31/506 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14

CPC classification number: C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14

Abstract: The present invention relates to pyridines, pyrimidines and derivatives thereof, (I) or a pharmaceutically acceptable salts thereof, wherein X 1 is N or CR 3 ; X 2 is N or CR 4 ; or -X 1 =X 2 - is -C(=O)-N(R a )- or -N(R a )-C(=O)-; X 3 is N or CR 4 ; X 4 is N or CR 4 ; X 5 is N or CR 6 ; X 6 is N or CR 6 ; wherein only 1, 2 or 3 of X 1 , X 2 , X 3 and X 4 are N; R 1 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.

Abstract translation: 本发明涉及吡啶，嘧啶及其衍生物，（I）或其药学上可接受的盐，其中X 1是N或CR 3; X 2是N或CR 4; 或-X 1 = X 2 - 是-C（= O）-N（R a） - 或-N（R 0） >一） - C（= O） - ; X 3是N或CR 4; X 4是N或CR 4; X 5是N或CR 6; X 6是N或CR 6; 其中X 1，X 2，X 3和X 4中仅有1,2或3是N; R 1是饱和的部分饱和或不饱和的含有0,1,2或3个选自N，O和S的原子的5-，6-或7-元环，其中环被 0,1,2或3个取代基。 还包括治疗炎症，类风湿性关节炎，佩吉特病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺β细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸窘迫综合征 （ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉退化，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应，阿尔茨海默病 ，中风，心肌梗塞，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV-1，HIV-2，HIV-3，巨细胞病毒 ），流感病毒，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的如上所述的化合物。

公开(公告)号：WO2005070932A3

公开(公告)日：2005-08-04

申请号：PCT/US2005/002013

申请日：2005-01-21

Applicant: AMGEN INC.

Inventor： FROHN, Michael, J. ,  HONG, Fang-Tsao ,  LIU, Longbin ,  LOPEZ, Patricia ,  SIEGMUND, Aaron, C. ,  TADESSE, Seifu ,  TAMAYO, Nuria

IPC: C07D487/04

Abstract: The present invention relates to pyrimidinones and pyridones and derivatives thereof, and pharmaceutically acceptable salts thereof. 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：WO2005019202A1

公开(公告)日：2005-03-03

申请号：PCT/US2004/027202

申请日：2004-08-20

Applicant: AMGEN INC.

Inventor： LIU, Longbin ,  LOPEZ, Patricia ,  BAJPAI, Manoj ,  SIEGMUND, Aaron, C.

IPC: C07D401/04

CPC classification number: C07D487/04 ,  C07D401/04

Abstract: The present invention relates to compounds having the general formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 is a saturated or unsaturated 5-, 6- or 7-membered, ring containing 0, 1, 2 or 3 atoms selected from N, 0 and S, wherein the ring may be fused with a benzo group, and is substituted by 0, 1 or 2 oxo groups, and wherein R 1 is additionally substituted; and R 2 is a substituted C 1-6 alkyl. Also included is a method of prophylaxis or 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.

Abstract translation: 本发明涉及具有通式（I）的化合物或其药学上可接受的盐，其中R 1是含有0,1,2或3个原子的饱和或不饱和的5-，6-或7-元环 选自N，O和S，其中所述环可以与苯并稠合，并且被0,1或2个氧代基取代，并且其中R 1另外被取代; R 2是取代的C 1-6烷基。 还包括预防或治疗炎症，类风湿性关节炎，佩吉特病，骨质疏松症，多发性骨髓瘤，葡萄膜炎，急性或慢性骨髓性白血病，胰腺β细胞破坏，骨关节炎，类风湿性脊椎炎，痛风性关节炎，炎性肠病，成人呼吸 窘迫综合征（ARDS），牛皮癣，克罗恩病，过敏性鼻炎，溃疡性结肠炎，过敏反应，接触性皮炎，哮喘，肌肉退化，恶病质，赖特综合征，I型糖尿病，II型糖尿病，骨吸收疾病，移植物抗宿主反应， 阿尔茨海默病，中风，心肌梗死，缺血再灌注损伤，动脉粥样硬化，脑外伤，多发性硬化，脑疟疾，败血症，败血性休克，中毒性休克综合征，发热，HIV-1，HIV-2，HIV-3，巨细胞病毒引起的肌痛 （CMV），流感，腺病毒，哺乳动物中的疱疹病毒或带状疱疹感染，包括给予有效量的化合物，如des 如上所述。