公开(公告)号：WO2016187308A1

公开(公告)日：2016-11-24

申请号：PCT/US2016/033088

申请日：2016-05-18

Applicant: AMGEN INC.

Inventor： CHEN, Ning ,  CHEN, Xiaoqi ,  CHEN, Yinhong ,  CHENG, Alan C. ,  CONNORS, Richard V. ,  DEIGNAN, Jeffrey ,  DRANSFIELD, Paul John ,  DU, Xiaohui ,  FU, Zice ,  HEATH, Julie Anne ,  HORNE, Daniel B. ,  HOUZE, Jonathan ,  KALLER, Matthew R. ,  KHAKOO, Aarif Yusuf ,  KOPECKY, David John ,  LAI, Su-Jen ,  MA, Zhihua ,  MCGEE, Lawrence R. ,  MEDINA, Julio C. ,  MIHALIC, Jeffrey T. ,  NISHIMURA, Nobuko ,  OLSON, Steven H. ,  PATTAROPONG, Vatee ,  SWAMINATH, Gayathri ,  WANG, Xiaodong ,  YANG, Kevin ,  YEH, Wen-Chen ,  DEBENEDETTO, Mikkel V. ,  FARRELL, Robert P. ,  HEDLEY, Simon J. ,  JUDD, Ted C. ,  KAYSER, Frank

IPC: C07D401/14 ,  C07D401/04 ,  C07D413/04 ,  A61K31/4196 ,  A61K31/4439 ,  A61P9/00

CPC classification number: C07D401/14 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/513 ,  A61K31/695 ,  A61K45/06 ,  C07B57/00 ,  C07B59/002 ,  C07B2200/05 ,  C07B2200/07 ,  C07C311/13 ,  C07D211/54 ,  C07D213/61 ,  C07D213/71 ,  C07D213/82 ,  C07D239/26 ,  C07D239/30 ,  C07D239/34 ,  C07D241/12 ,  C07D241/18 ,  C07D241/24 ,  C07D249/08 ,  C07D295/16 ,  C07D401/04 ,  C07D401/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07F7/08

Abstract: Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures where the definitions of the variables are provided herein.

Abstract translation: 式I和式II的化合物，其药学上可接受的盐，前述任何一种的立体异构体或其混合物是APJ受体的激动剂，并且可用于治疗心血管和其它病症。 式I和式II的化合物具有以下结构，其中本文提供变量的定义。

公开(公告)号：WO2013049250A1

公开(公告)日：2013-04-04

申请号：PCT/US2012/057389

申请日：2012-09-26

Applicant: AMGEN INC. ,  BARTBERGER, Michael D. ,  BECK, Hilary Plake ,  CHEN, Xiaoqi ,  CONNORS, Richard V. ,  DEIGNAN, Jeffrey ,  DUQUETTE, Jason A. ,  EKSTEROWICZ, John ,  FOX, Brian M. ,  FU, Jiasheng ,  GONZALEZ BUENROSTRO, Ana ,  GONZALEZ LOPEZ DE TURISO, Felix ,  GUSTIN, Darin J. ,  HEATH, Julie A. ,  JOHNSON, Michael G. ,  KAYSER, Frank ,  KOPECKY, David J. ,  LI, Yihong ,  LI, Zhihong ,  MA, Zhihua ,  MCINTOSH, Joel ,  MEDINA, Julio C. ,  MIHALIC, Jeffrey T. ,  OLSON, Steven H. ,  REW, Yosup ,  ROVETO, Philip M. ,  SCHMITT, Michael J. ,  SUN, Daqing ,  WANG, Xiaodong ,  WANSKA, Malgorzata ,  WEATHERS, Christine ,  YAN, Xuelei

Inventor： BARTBERGER, Michael D. ,  BECK, Hilary Plake ,  CHEN, Xiaoqi ,  CONNORS, Richard V. ,  DEIGNAN, Jeffrey ,  DUQUETTE, Jason A. ,  EKSTEROWICZ, John ,  FOX, Brian M. ,  FU, Jiasheng ,  GONZALEZ BUENROSTRO, Ana ,  GONZALEZ LOPEZ DE TURISO, Felix ,  GUSTIN, Darin J. ,  HEATH, Julie A. ,  JOHNSON, Michael G. ,  KAYSER, Frank ,  KOPECKY, David J. ,  LI, Yihong ,  LI, Zhihong ,  MA, Zhihua ,  MCINTOSH, Joel ,  MEDINA, Julio C. ,  MIHALIC, Jeffrey T. ,  OLSON, Steven H. ,  REW, Yosup ,  ROVETO, Philip M. ,  SCHMITT, Michael J. ,  SUN, Daqing ,  WANG, Xiaodong ,  WANSKA, Malgorzata ,  WEATHERS, Christine ,  YAN, Xuelei

IPC: C07D265/06 ,  C07D413/04 ,  C07D413/10 ,  C07D417/04 ,  C07D413/12

CPC classification number: C07D413/04 ,  C07D265/06 ,  C07D265/32 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04

Abstract: The present invention provides MDM2 inhibitor compounds of Formula I or II, or the pharmaceutically acceptable salts thereof, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

Abstract translation: 本发明提供式I或II的MDM2抑制剂化合物或其药学上可接受的盐，其中变量如上所定义，哪些化合物可用作治疗剂，特别是用于治疗癌症。 本发明还涉及含有MDM2抑制剂的药物组合物。

公开(公告)号：WO2014130470A1

公开(公告)日：2014-08-28

申请号：PCT/US2014/016971

申请日：2014-02-18

Applicant: AMGEN INC.

Inventor： BARTBERGER, Michael, D. ,  BECK, Hilary, Plake ,  DEGRAFFENREID, Michael, R. ,  FOX, Brian, M. ,  GONZALEZ LOPEZ DE TURISO, Felix ,  JULIAN, Lisa, D. ,  KAYSER, Frank ,  MEDINA, Julio, C. ,  OLSON, Steven, H. ,  REW, Yosup ,  ROVETO, Philip, M. ,  SUN, Daqing ,  YAN, Xuelei

IPC: C07D265/32 ,  C07D413/04 ,  C07D413/06 ,  C07D279/12 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/54 ,  A61P35/00

CPC classification number: C07D265/32 ,  C07D279/12 ,  C07D413/04 ,  C07D413/06 ,  C07D487/04

Abstract: The present invention provides MDM2 inhibitor compounds of Formula (I), or the pharmaceutically acceptable salts thereof, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

Abstract translation: 本发明提供式（I）的MDM2抑制剂化合物或其药学上可接受的盐，其中变量如上所定义，哪些化合物可用作治疗剂，特别是用于治疗癌症。 本发明还涉及含有MDM2抑制剂的药物组合物。

公开(公告)号：WO2006130160A2

公开(公告)日：2006-12-07

申请号：PCT/US2005/025725

申请日：2005-07-19

Applicant: AMGEN INC. ,  NUNES, Joseph, J. ,  MARTIN, Matthew, W. ,  WHITE, Ryan ,  MCGOWAN, David ,  BEMIS, Jean, E. ,  KAYSER, Frank ,  FU, Jiasheng ,  LIU, Jinqian ,  JIAO, XianYun

Inventor： NUNES, Joseph, J. ,  MARTIN, Matthew, W. ,  WHITE, Ryan ,  MCGOWAN, David ,  BEMIS, Jean, E. ,  KAYSER, Frank ,  FU, Jiasheng ,  LIU, Jinqian ,  JIAO, XianYun

CPC classification number: C07D491/04 ,  C07D491/14

Abstract: The present invention relates to furanopyridine compounds having the general Formula I (I) and stereoisomers, tautomers, solvates, pharmaceutically acceptable salts and derivatives, and prodrugs thereof. The invention also includes pharmaceutical compositions comprising a compound of Formula I, methods of modulating Lck and ACK-1 enzymes and of treating various related diseases and conditions, including inflammation, inhibition of T cell activation, proliferation, arthritis, organ transplant, ischemic or reperfusion injury, myocardial infarction, stroke, multiple sclerosis, inflammatory bowel disease, Crohn's disease, lupus, hypersensitivity, type 1 diabetes, psoriasis, dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism, Addison's disease, autoimmune diseases, glomerulonephritis, allergic diseases, asthma, hayfever, eczema, cancer, colon carcinoma, thymoma, just to name a few, in a mammal, comprising administering to the mammal a therapeutically effective amount a compound of Formula I, as described above, and methods of manufacturing medicaments comprising the compound of Formula I.

Abstract translation: 本发明涉及具有通式I（I）的呋喃并吡啶化合物及其立体异构体，互变异构体，溶剂合物，药学上可接受的盐和衍生物及其前药。 本发明还包括药物组合物，其包含式I化合物，调节Lck和ACK-1酶的方法以及治疗各种相关疾病和病症，包括炎症，T细胞活化抑制，增殖，关节炎，器官移植，缺血或再灌注 损伤，心肌梗塞，中风，多发性硬化，炎性肠病，克罗恩病，狼疮，超敏反应，1型糖尿病，牛皮癣，皮炎，桥本氏甲状腺炎，干燥综合征，自身免疫性甲状腺功能亢进，艾迪生病，自身免疫性疾病，肾小球肾炎，过敏性疾病，哮喘 ，干草组织，湿疹，癌症，结肠癌，胸腺瘤，仅举几个例子，在哺乳动物中，包括向哺乳动物施用治疗有效量的如上所述的式I化合物和制备包含以下化合物的药物的方法： 一级方程式

公开(公告)号：WO2006004658A3

公开(公告)日：2006-01-12

申请号：PCT/US2005/022727

申请日：2005-06-29

Applicant: AMGEN INC. ,  BUCHANAN, John L. ,  BUCKNER, William H. ,  BURKITT, Simon A. ,  DIMAURO, Erin F. ,  FARTHING, Christopher N. ,  FRENKEL, Alexander David ,  HARRISON, Martin J. ,  KAYSER, Frank ,  LIU, Jinqian ,  LIVELY, Sarah E. ,  MARSHALL, Teresa L. ,  MCGOWAN, David C. ,  SHARMA, Rajiv ,  SHUTTLEWORTH, Stephen Joseph ,  ZHU, Xiaotian

Inventor： BUCHANAN, John L. ,  BUCKNER, William H. ,  BURKITT, Simon A. ,  DIMAURO, Erin F. ,  FARTHING, Christopher N. ,  FRENKEL, Alexander David ,  HARRISON, Martin J. ,  KAYSER, Frank ,  LIU, Jinqian ,  LIVELY, Sarah E. ,  MARSHALL, Teresa L. ,  MCGOWAN, David C. ,  SHARMA, Rajiv ,  SHUTTLEWORTH, Stephen Joseph ,  ZHU, Xiaotian

IPC: C07D498/04 ,  A61K31/519

Abstract: The present invention relates to furanopyrimidine compounds having the general Formula (I) and stereoisomers, tautomers, solvates, pharmaceutically acceptable salts and derivatives, and prodrugs thereof. The invention also includes pharmaceutical compositions comprising a compound of Formula (I), methods of treating various diseases and conditions in a mammal, including inflammation, inhibition of T cell activation, proliferation, arthritis, organ transplant, ischemic or reperfusion injury, myocardial infarction, stroke, multiple sclerosis, inflammatory bowel disease, Crohn's disease, lupus, hypersensitivity, type 1 diabetes, psoriasis, dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism, Addison's disease, autoimmune diseases, glomerulonephritis, allergic diseases, asthma, hayfever, eczema, cancer, colon carcinoma and thymoma, comprising administering to the mammal a therapeutically effective amount of a compound of Formula (I). The invention also relates to methods of manufacturing medicaments, which comprise one or more compounds of Formula (I).

公开(公告)号：WO2018097945A1

公开(公告)日：2018-05-31

申请号：PCT/US2017/059824

申请日：2017-11-03

Applicant: AMGEN INC.

Inventor： CHEN, Ning ,  CHEN, Xiaoqi ,  CHEN, Yinhong ,  CHENG, Alan C. ,  CONNORS, Richard V. ,  DEIGNAN, Jeffrey ,  DRANSFIELD, Paul John ,  DU, Xiaohui ,  FU, Zice ,  HARVEY, James S. ,  HEATH, Julie Anne ,  HEUMANN, Lars V. ,  HORNE, Daniel B. ,  HOUZE, Jonathan ,  KALLER, Matthew R. ,  KAYSER, Frank ,  KHAKOO, Aarif Yusuf ,  KOPECKY, David J. ,  LAI, Su-Jen ,  MA, Zhihua ,  MEDINA, Julio C. ,  MIHALIC, Jeffrey T. ,  NISHIMURA, Nobuko ,  OLSON, Steven H. ,  PATTAROPONG, Vatee ,  SWAMINATH, Gayathri ,  WANG, Xiaodong ,  WANSKA, Malgorzata ,  YANG, Kevin ,  YEH, Wen-Chen

IPC: C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D487/04 ,  A61K31/341 ,  A61K31/4196 ,  A61P9/00 ,  A61P9/02

Abstract: Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

公开(公告)号：WO2018097944A1

公开(公告)日：2018-05-31

申请号：PCT/US2017/059822

申请日：2017-11-03

Applicant: AMGEN INC.

Inventor： BROWN, Matthew ,  CHEN, Ning ,  CHEN, Xiaoqi ,  CHEN, Yinhong ,  CHENG, Alan C. ,  CONNORS, Richard V. ,  DEIGNAN, Jeffrey ,  DRANSFIELD, Paul John ,  DU, Xiaohui ,  FU, Zice ,  HARVEY, James S. ,  HEATH, Julie Anne ,  HEUMANN, Lars V. ,  HOUZE, Jonathan ,  KAYSER, Frank ,  KHAKOO, Aarif Yusuf ,  KOPECKY, David J. ,  LAI, Su-Jen ,  MA, Zhihua ,  MEDINA, Julio C. ,  MIHALIC, Jeffrey T. ,  OLSON, Steven H. ,  PATTAROPONG, Vatee ,  SWAMINATH, Gayathri ,  WANG, Xiaodong ,  WANSKA, Malgorzata ,  YEH, Wen-Chen

IPC: C07D307/54 ,  C07D405/04 ,  C07D405/14 ,  A61K31/341 ,  A61K31/4196 ,  A61P9/02 ,  A61P9/00

Abstract: Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula (I) and Formula (II) have the following structures: (I); (II). Intermediates (V) are also claimed.

公开(公告)号：WO2011153509A1

公开(公告)日：2011-12-08

申请号：PCT/US2011/039184

申请日：2011-06-03

Applicant: AMGEN INC. ,  BARTBERGER, Michael David ,  GONZALEZ BUENROSTRO, Ana ,  BECK, Hilary Plake ,  CHEN, Xiaoqi ,  CONNORS, Richard Victor ,  DEIGNAN, Jeffery ,  DUQUETTE, Jason ,  EKSTEROWICZ, John ,  FISHER, Benjamin ,  FOX, Brian Matthew ,  FU, Jiasheng ,  FU, Zice ,  GONZALEZ LOPEZ DE TURISO, Felix ,  GRIBBLE, JR., Michael William ,  GUSTIN, Darin James ,  HEATH, Julie Anne ,  HUANG, Xin ,  JIAO, Xianyun ,  JOHNSON, Michael ,  KAYSER, Frank ,  KOPECKY, David John ,  LAI, Sujen ,  LI, Yihong ,  LI, Zhihong ,  LIU, Jiwen ,  LOW, Jonathan Dante ,  LUCAS, Brian Stuart ,  MA, Zhihua ,  MCGEE, Lawrence ,  MCINTOSH, Joel ,  MCMINN, Dustin ,  MEDINA, Julio Cesar ,  MIHALIC, Jeffrey Thomas ,  OLSON, Steven Howard ,  REW, Yosup ,  ROVETO, Philip Marley ,  SUN, Daqing ,  WANG, Xiaodong ,  WANG, Yingcai ,  YAN, Xuelei ,  YU, Ming ,  ZHU, Jiang

Inventor： BARTBERGER, Michael David ,  GONZALEZ BUENROSTRO, Ana ,  BECK, Hilary Plake ,  CHEN, Xiaoqi ,  CONNORS, Richard Victor ,  DEIGNAN, Jeffery ,  DUQUETTE, Jason ,  EKSTEROWICZ, John ,  FISHER, Benjamin ,  FOX, Brian Matthew ,  FU, Jiasheng ,  FU, Zice ,  GONZALEZ LOPEZ DE TURISO, Felix ,  GRIBBLE, JR., Michael William ,  GUSTIN, Darin James ,  HEATH, Julie Anne ,  HUANG, Xin ,  JIAO, Xianyun ,  JOHNSON, Michael ,  KAYSER, Frank ,  KOPECKY, David John ,  LAI, Sujen ,  LI, Yihong ,  LI, Zhihong ,  LIU, Jiwen ,  LOW, Jonathan Dante ,  LUCAS, Brian Stuart ,  MA, Zhihua ,  MCGEE, Lawrence ,  MCINTOSH, Joel ,  MCMINN, Dustin ,  MEDINA, Julio Cesar ,  MIHALIC, Jeffrey Thomas ,  OLSON, Steven Howard ,  REW, Yosup ,  ROVETO, Philip Marley ,  SUN, Daqing ,  WANG, Xiaodong ,  WANG, Yingcai ,  YAN, Xuelei ,  YU, Ming ,  ZHU, Jiang

IPC: C07D211/40 ,  C07D401/04 ,  C07D401/06 ,  C07D407/04 ,  C07D407/06 ,  C07D409/04 ,  C07D413/06 ,  C07D417/06 ,  C07D471/20 ,  C07D279/02 ,  C07D401/12 ,  C07D498/08 ,  C07D498/20 ,  A61K31/4412 ,  A61P35/00

CPC classification number: C07D211/76 ,  C07D221/20 ,  C07D279/02 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D407/04 ,  C07D407/06 ,  C07D409/04 ,  C07D409/12 ,  C07D413/06 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/10 ,  C07D491/08 ,  C07D491/153 ,  C07D498/08 ,  C07D498/14 ,  C07D498/20

Abstract: The present invention provides MDM2 inhibitor compounds of Formula (I), wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

Abstract translation: 本发明提供式（I）的MDM2抑制剂化合物，其中变量如上所定义，哪些化合物可用作治疗剂，特别是用于治疗癌症。 本发明还涉及含有MDM2抑制剂的药物组合物。

公开(公告)号：WO2007024680A1

公开(公告)日：2007-03-01

申请号：PCT/US2006/032314

申请日：2006-08-18

Applicant: AMGEN INC. ,  BUCHANAN, John L. ,  BUCKNER, William H. ,  CARDOZO, Mario G. ,  DIMAURO, Erin F. ,  FU, Jiasheng ,  HAO, Xiaolin ,  JIAO, XianYun ,  KAYSER, Frank ,  KOPECKY, David J. ,  MASSE, Craig E. ,  TOMLINSON, Susan A. ,  WHITE, Ryan ,  ZHU, Xiaotian

Inventor： BUCHANAN, John L. ,  BUCKNER, William H. ,  CARDOZO, Mario G. ,  DIMAURO, Erin F. ,  FU, Jiasheng ,  HAO, Xiaolin ,  JIAO, XianYun ,  KAYSER, Frank ,  KOPECKY, David J. ,  MASSE, Craig E. ,  TOMLINSON, Susan A. ,  WHITE, Ryan ,  ZHU, Xiaotian

IPC: C07D487/04 ,  C07D231/56 ,  C07D403/06 ,  C07D405/06 ,  C07D401/14 ,  A61K31/519 ,  A61K31/416 ,  A61P19/00 ,  A61P17/00 ,  A61P35/00

CPC classification number: C07D403/06 ,  C07D231/56 ,  C07D401/14 ,  C07D405/06 ,  C07D487/04

Abstract: The present invention relates to compounds of Formula (I) or a stereomer, a tautomer, a solvate, a pharmaceutically acceptable salt, or a prodrug thereof, pharmaceutical formulations containing the compounds, methods of treatments using the compounds, for example, protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders and methods of preparing medicaments comprising the compounds.

Abstract translation: 本发明涉及式（I）的化合物或立体异构体，互变异构体，溶剂化物，药学上可接受的盐或其前药，含有该化合物的药物制剂，使用该化合物的治疗方法，例如蛋白酪氨酸激酶 - 相关疾病如免疫学和肿瘤学疾病以及制备包含该化合物的药物的方法。

公开(公告)号：WO2008002591A3

公开(公告)日：2008-01-03

申请号：PCT/US2007/014873

申请日：2007-06-26

Applicant: AMGEN INC ,  KAYSER, Frank ,  LABELLE, Marc ,  SHAN, Bei ,  ZHANG, Jian ,  ZHOU, Mingyue

Inventor： KAYSER, Frank ,  LABELLE, Marc ,  SHAN, Bei ,  ZHANG, Jian ,  ZHOU, Mingyue

IPC: A61K31/497 ,  A61P9/10 ,  A61P25/28 ,  A61P9/12 ,  A61P3/00 ,  A61P3/06

Abstract: The invention provides compounds, pharmaceutical compositions and methods for treating atherosclerosis, inflammation, thrombosis and other conditions and for decreasing or prevention of accumulation of cholesterol in a subject by modifying LCAT polypeptide.