公开(公告)号：WO2022020550A1

公开(公告)日：2022-01-27

申请号：PCT/US2021/042702

申请日：2021-07-22

申请人： MERCK SHARP & DOHME CORP. ,  ALI, Amjad ,  BOYCE, Christopher, W. ,  CUMMING, Jared, N. ,  DEMONG, Duane ,  GRAHAM, Thomas, H. ,  GUDIPATI, Subrahmanyam ,  HOOVER, Andrew, J. ,  HUANG, Xianhai ,  KUANG, Rongze ,  KIM, Jae-Hun ,  KELLY, Joseph, M. ,  LIM, Yeon-Hee ,  LO, Michael, Man-Chu ,  MORENO, Jesus ,  SU, Jing ,  WU, Heping ,  XIAO, Dong ,  YU, Younong ,  ZHU, Xiaohong

发明人： ALI, Amjad ,  BOYCE, Christopher, W. ,  CUMMING, Jared, N. ,  DEMONG, Duane ,  GRAHAM, Thomas, H. ,  GUDIPATI, Subrahmanyam ,  HOOVER, Andrew, J. ,  HUANG, Xianhai ,  KUANG, Rongze ,  KIM, Jae-Hun ,  KELLY, Joseph, M. ,  LIM, Yeon-Hee ,  LO, Michael, Man-Chu ,  MORENO, Jesus ,  SU, Jing ,  WU, Heping ,  XIAO, Dong ,  YU, Younong ,  ZHU, Xiaohong

IPC分类号： A61K31/519 ,  C07D487/04 ,  C07D487/08 ,  C07D513/04

摘要： The present invention provides compounds of the structural Formula (I) and pharmaceutically acceptable salts thereof, wherein, are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.

公开(公告)号：WO2021202254A1

公开(公告)日：2021-10-07

申请号：PCT/US2021/024267

申请日：2021-03-26

申请人： MERCK SHARP & DOHME CORP. ,  HICKS, Jacqueline, D. ,  ALI, Amjad ,  DEBENHAM, John, S. ,  DONOFRIO, Anthony ,  FU, Wenlang ,  GAO, Ying-Duo ,  HRUZA, Alan, W. ,  LIM, Yeon-Hee ,  LOMBARDO, Matthew, J. ,  NIZNER, Peter ,  SO, Sung-Sau ,  TAN, Zheng ,  TATOSIAN, Daniel, A. ,  XIAO, Dong ,  YANG, Dexi ,  YU, Yang

发明人： HICKS, Jacqueline, D. ,  ALI, Amjad ,  DEBENHAM, John, S. ,  DONOFRIO, Anthony ,  FU, Wenlang ,  GAO, Ying-Duo ,  HRUZA, Alan, W. ,  LIM, Yeon-Hee ,  LOMBARDO, Matthew, J. ,  NIZNER, Peter ,  SO, Sung-Sau ,  TAN, Zheng ,  TATOSIAN, Daniel, A. ,  XIAO, Dong ,  YANG, Dexi ,  YU, Yang

IPC分类号： A61K31/444 ,  A61K31/4709 ,  A61K31/4725

摘要： The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XI activation inhibitors.

公开(公告)号：WO2014101373A1

公开(公告)日：2014-07-03

申请号：PCT/CN2013/076853

申请日：2013-06-06

申请人： MERCK SHARP & DOHME CORP. ,  ALI, Amjad ,  LO, Michael Man-Chu ,  LIM, Yeon-Hee ,  STAMFORD, Andrew ,  KUANG, Rongze ,  TEMPEST, Paul ,  YU, Younong ,  HUANG, Xianhai ,  HENDERSON, Timothy J. ,  KIM, Jae-Hun ,  BOYCE, Christopher ,  TING, Pauline ,  ZHENG, Junying ,  METZGER, Edward ,  ZORN, Nicolas ,  XIAO, Dong ,  GALLO, Gioconda V. ,  WON, Walter ,  WU, Heping

发明人： ALI, Amjad ,  LO, Michael Man-Chu ,  LIM, Yeon-Hee ,  STAMFORD, Andrew ,  KUANG, Rongze ,  TEMPEST, Paul ,  YU, Younong ,  HUANG, Xianhai ,  HENDERSON, Timothy J. ,  KIM, Jae-Hun ,  BOYCE, Christopher ,  TING, Pauline ,  ZHENG, Junying ,  METZGER, Edward ,  ZORN, Nicolas ,  XIAO, Dong ,  GALLO, Gioconda V. ,  WON, Walter ,  WU, Heping

IPC分类号： C07D519/00 ,  A61K31/519 ,  A61P25/16

CPC分类号： C07D519/00 ,  C07D487/04

摘要： Disclosed are compounds of heterobicyclo-substituted [1,2,4]triazolo[1,5-c]quinazolin-5-amine herein, which have specific binding on an A 2A -receptor and are useful for quantifying in vivo receptor-site occupancy of various compounds which have an affinity for binding to an A 2A -receptor.

摘要翻译： 公开了本文中具有与A2A受体的特异性结合的异二环取代的[1,2,4]三唑并[1,5-c]喹唑啉-5-胺的化合物，并且可用于定量体内受体位点占有率 具有与A2A受体结合的亲和力的各种化合物。

公开(公告)号：WO2009085880A2

公开(公告)日：2009-07-09

申请号：PCT/US2008087301

申请日：2008-12-18

申请人： SCHERING CORP ,  WANG HONGWU ,  LIM YEON HEE ,  LEE YOON JON ,  BITAR REMA DANIELLE ,  ANTHES JOHN C ,  MCCORMICK KEVIN D ,  HEY JOHN A ,  ASLANIAN ROBERT G ,  BIJU PURAKKATTLE J ,  BERLIN MICHAEL Y ,  SOLOMON DANIEL M

发明人： ANTHES JOHN C ,  MCCORMICK KEVIN D ,  HEY JOHN A ,  ASLANIAN ROBERT G ,  BIJU PURAKKATTLE J ,  BERLIN MICHAEL Y ,  SOLOMON DANIEL M

IPC分类号： C07J43/00 ,  A61K31/573 ,  A61K31/58 ,  A61P5/44 ,  C07J31/00 ,  C07J71/00

CPC分类号： C07J43/003 ,  C07J31/006 ,  C07J71/0031

摘要： The present invention provides compounds of Formula (VII) and 11-keto analogs thereof, and pharmaceutically acceptable salts, solvates, esters, prodrugs, tautomers, and isomers of said compounds and said 11-keto analogs, having the general structure formula (VII): wherein L, R1, R2, R3, R4, and R5 are selected independently of each other and as defined herein. Also provided are pharmaceutical compositions, methods of preparing, and methods of using such compounds in the treatment and prophylaxis of a wide range of immune, autoimmune, and inflammatory diseases and conditions. The novel compounds of the present invention possess useful pharmacological activity while having unexpectedly low systemic activiy. Thus, the compounds of the invention represent a safer alternative to those known glucocorticoids which have poor side-effect profiles.

摘要翻译： 本发明提供具有通式（Ⅶ）的所述化合物和所述11-酮类似物的式（Ⅶ）化合物及其11-酮类似物及其药学上可接受的盐，溶剂合物，酯，前药，互变异构体和异构体， ：其中L，R 1，R 2，R 3，R 4和R 5彼此独立地选择并如本文所定义。 还提供了药物组合物，制备方法和使用这些化合物在治疗和预防广泛范围的免疫，自身免疫和炎性疾病和病症中的方法。 本发明的新化合物具有有用的药理活性，同时具有出人意料的低全身活性。 因此，本发明的化合物代表具有差的副作用特征的已知糖皮质激素的更安全的替代方案。

公开(公告)号：WO2022076495A1

公开(公告)日：2022-04-14

申请号：PCT/US2021/053680

申请日：2021-10-06

申请人： MERCK SHARP & DOHME CORP. ,  LIM, Yeon-Hee ,  ASHLEY, Eric, R. ,  BAO, Jianming ,  CHENG, Chen ,  ROANE, James, P. ,  SOUTHGATE, Emma Helen

发明人： LIM, Yeon-Hee ,  ASHLEY, Eric, R. ,  BAO, Jianming ,  CHENG, Chen ,  ROANE, James, P. ,  SOUTHGATE, Emma Helen

IPC分类号： C07D235/26 ,  C07D409/12 ,  C07D409/14 ,  C07D471/04 ,  A61P3/10 ,  A61K31/4184

摘要： Invented are compounds of Formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

公开(公告)号：WO2019118313A1

公开(公告)日：2019-06-20

申请号：PCT/US2018/064649

申请日：2018-12-10

申请人： MERCK SHARP & DOHME CORP. ,  ALI, Amjad ,  LIM, Yeon-Hee ,  GALLO-ETIENNE, Gioconda, V. ,  KELLY, Joseph, Michael ,  BERLIN, Michael ,  TING, Pauline ,  TAGAT, Jayaram, R. ,  XIAO, Dong ,  KUANG, Rongze ,  WU, Heping ,  WANG, Hongwu

发明人： ALI, Amjad ,  LIM, Yeon-Hee ,  GALLO-ETIENNE, Gioconda, V. ,  KELLY, Joseph, Michael ,  BERLIN, Michael ,  TING, Pauline ,  TAGAT, Jayaram, R. ,  XIAO, Dong ,  KUANG, Rongze ,  WU, Heping ,  WANG, Hongwu

IPC分类号： A61K31/4188 ,  A61K31/505 ,  A61K31/519 ,  C07D247/00 ,  C07D247/02 ,  C07D255/00

摘要： Disclosed are compounds having the structure of Formula I, or a pharmaceutically acceptable salt of any thereof: wherein: "Z" and R1 are defined herein, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.

公开(公告)号：WO2017074832A1

公开(公告)日：2017-05-04

申请号：PCT/US2016/058362

申请日：2016-10-24

申请人： MERCK SHARP & DOHME CORP. ,  XU, Jiayi ,  ALI, Amjad ,  ZHOU, Wei ,  GAO, Ying-Duo ,  EDMONDSON, Scott, D. ,  MERTZ, Eric ,  NEELAMKAVIL, Santhosh, F. ,  LIU, Weiguo ,  SUN, Wanying ,  SHEN, Dong-Ming ,  HARPER, Bart ,  ZHU, Cheng ,  BARA, Thomas ,  LIM, Yeon-Hee ,  YANG, Meng

发明人： XU, Jiayi ,  ALI, Amjad ,  ZHOU, Wei ,  GAO, Ying-Duo ,  EDMONDSON, Scott, D. ,  MERTZ, Eric ,  NEELAMKAVIL, Santhosh, F. ,  LIU, Weiguo ,  SUN, Wanying ,  SHEN, Dong-Ming ,  HARPER, Bart ,  ZHU, Cheng ,  BARA, Thomas ,  LIM, Yeon-Hee ,  YANG, Meng

IPC分类号： A61K31/44 ,  A61K31/4418 ,  A61K31/4427 ,  C07D213/02 ,  C07D213/04 ,  C07D401/06

CPC分类号： C07D513/08 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D413/14 ,  C07D471/08 ,  C07D487/04 ,  C07D487/08

摘要： The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma Kallikrein.

摘要翻译： 本发明提供式（I）化合物和包含一种或多种所述化合物的药物组合物，以及使用所述化合物治疗或预防血栓形成，栓塞，高凝状态或纤维化改变的方法。 这些化合物是选择性因子XIa抑制剂或因子XIa和血浆激肽释放酶的双重抑制剂。

公开(公告)号：WO2015031221A1

公开(公告)日：2015-03-05

申请号：PCT/US2014/052442

申请日：2014-08-25

申请人： MERCK SHARP & DOHME CORP. ,  ALI, Amjad ,  GALLO, Gioconda, V. ,  HENDERSON, Timothy, J. ,  KUANG, Rongze ,  LIM, Yeon-Hee ,  LO, Michael Man-Chu ,  METZGER, Edward ,  RUIZ, Manuel de Lera ,  STAMFORD, Andrew ,  TEMPEST, Paul ,  WHITEHEAD, Brent ,  WU, Heping

发明人： ALI, Amjad ,  GALLO, Gioconda, V. ,  HENDERSON, Timothy, J. ,  KUANG, Rongze ,  LIM, Yeon-Hee ,  LO, Michael Man-Chu ,  METZGER, Edward ,  RUIZ, Manuel de Lera ,  STAMFORD, Andrew ,  TEMPEST, Paul ,  WHITEHEAD, Brent ,  WU, Heping

IPC分类号： A01N43/58 ,  A01N43/60

CPC分类号： C07D519/00 ,  C07D491/147

摘要： The present invention is directed to 2,2-difluorodioxolo compounds that are antagonists of A 2A receptor. The present invention is also directed to uses of the 2,2- difluorodioxolo compounds described herein in the potential treatment or prevention of 5 neurological disorders and diseases in which A 2A receptor are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds and to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which A 2A receptors are involved.

摘要翻译： 本发明涉及作为A2A受体拮抗剂的2,2-二氟二氧代己基化合物。 本发明还涉及本文所述的2,2-二氟二氧代己基化合物在潜在的治疗或预防涉及A2A受体的5种神经障碍和疾病中的用途。 本发明还涉及包含这些化合物的药物组合物以及这些药物组合物用于预防或治疗其中涉及A2A受体的疾病的用途。

公开(公告)号：WO2014105666A1

公开(公告)日：2014-07-03

申请号：PCT/US2013/076781

申请日：2013-12-20

申请人： MERCK SHARP & DOHME CORP. ,  ALI, Amjad ,  LO, Michael Man-Chu ,  LIM, Yeon-Hee ,  STAMFORD, Andrew ,  KUANG, Rongze ,  TEMPEST, Paul ,  YU, Younong ,  HUANG, Xianhai ,  HENDERSON, Timothy, J. ,  KIM, Jae-Hun ,  BOYCE, Christopher ,  TING, Pauline ,  ZHENG, Junying ,  METZGER, Edward ,  ZORN, Nicolas ,  XIAO, Dong ,  GALLO, Gioconda, V. ,  WON, Walter ,  WU, Heping

发明人： ALI, Amjad ,  LO, Michael Man-Chu ,  LIM, Yeon-Hee ,  STAMFORD, Andrew ,  KUANG, Rongze ,  TEMPEST, Paul ,  YU, Younong ,  HUANG, Xianhai ,  HENDERSON, Timothy, J. ,  KIM, Jae-Hun ,  BOYCE, Christopher ,  TING, Pauline ,  ZHENG, Junying ,  METZGER, Edward ,  ZORN, Nicolas ,  XIAO, Dong ,  GALLO, Gioconda, V. ,  WON, Walter ,  WU, Heping

IPC分类号： A61K31/4985 ,  A61K31/519 ,  C07D487/04 ,  A61P25/16

CPC分类号： C07D519/00 ,  C07D487/04

摘要： Disclosed are compounds of Formula Gl (structurally represented): where "RG3" "Rd1" to "Rd4", "n", "m", "p", "W", "X", "Y", and "Z" are defined herein which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2a receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions.

摘要翻译： 公开了式（式III）化合物：其中“RG3”“Rd1”至“Rd4”，“n”，“m”，“p”，“W”，“X”，“Y” “在本文中定义为哪些化合物是A2A受体的拮抗剂。 本文还公开了本文所述的化合物作为A2a受体的拮抗剂的潜在治疗或预防涉及A2A受体的神经障碍和疾病的用途。 本文还公开了包含这些化合物的药物组合物和这些药物组合物的用途。

公开(公告)号：WO2014105664A1

公开(公告)日：2014-07-03

申请号：PCT/US2013/076775

申请日：2013-12-20

申请人： MERCK SHARP & DOHME CORP. ,  ALI, Amjad ,  LO, Michael Man-Chu ,  LIM, Yeon-Hee ,  STAMFORD, Andrew ,  KUANG, Rongze ,  TEMPEST, Paul ,  YU, Younong ,  BERLIN, Michael ,  TING, Pauline ,  ZHOU, Gang ,  YU, Tao ,  BOYCE, Christopher ,  KELLY, Joseph Michael ,  TAGAT, Jayaram, R. ,  ZHENG, Junying ,  HUANG, Xianhai ,  ZHOU, Wei ,  KIM, Jae-Hun ,  ZORN, Nicolas ,  XIAO, Dong ,  GALLO, Gioconda, V. ,  WON, Walter ,  WU, Heping ,  ANAND, Rajan

发明人： ALI, Amjad ,  LO, Michael Man-Chu ,  LIM, Yeon-Hee ,  STAMFORD, Andrew ,  KUANG, Rongze ,  TEMPEST, Paul ,  YU, Younong ,  BERLIN, Michael ,  TING, Pauline ,  ZHOU, Gang ,  YU, Tao ,  BOYCE, Christopher ,  KELLY, Joseph Michael ,  TAGAT, Jayaram, R. ,  ZHENG, Junying ,  HUANG, Xianhai ,  ZHOU, Wei ,  KIM, Jae-Hun ,  ZORN, Nicolas ,  XIAO, Dong ,  GALLO, Gioconda, V. ,  WON, Walter ,  WU, Heping ,  ANAND, Rajan

IPC分类号： A61K31/4985 ,  A61K31/519

CPC分类号： C07D487/04 ,  C07D487/08 ,  C07D487/18 ,  C07D513/04

摘要： Disclosed are compounds of Formula A: (structurally represented) where "RG1", "RG2a", "RG4", "RG5", "MG1", "n" and "m" are defined herein which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2a receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions.

摘要翻译： 公开了式A化合物（结构上表示），其中“RG1”，“RG2a”，“RG4”，“RG5”，“MG1”，“n”和“m”在本文中定义为哪些化合物是A2A受体的拮抗剂。 本文还公开了本文所述的化合物作为A2a受体的拮抗剂的潜在治疗或预防涉及A2A受体的神经障碍和疾病的用途。 本文还公开了包含这些化合物的药物组合物和这些药物组合物的用途。