公开(公告)号：EP2097387B1

公开(公告)日：2016-05-04

申请号：EP08714220.4

申请日：2008-02-20

申请人： Merck Sharp & Dohme Corp. ,  Pharmacopeia, LLC

发明人： ZHU, Zhaoning ,  MCKITTRICK, Brian ,  SUN, Zhong-Yue ,  YE, Yuanzan, C. ,  VOIGT, Johannes, H. ,  STRICKLAND, Corey ,  SMITH, Elizabeth, M. ,  STAMFORD, Andrew ,  GREENLEE, William, J. ,  MAZZOLA, JR., Robert, D. ,  CALDWELL, John ,  CUMMING, Jared, N. ,  WANG, Lingyan ,  WU, Yusheng ,  ISERLOH, Ulrich ,  LIU, Xiaoxiang ,  HUANG, Ying ,  LI, Guoqing ,  PAN, Jianping ,  MISIASZEK, Jeffrey, A. ,  GUO, Tao ,  LE, Thuy X. H. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D. ,  HUNTER, Rachael, C. ,  MORRIS, Michelle, L. ,  GU, Huizhong ,  QIAN, Gang ,  TADESSE, Dawit ,  LAI, Gaifa ,  DUO, Jingqi ,  QU, Chuanxing ,  SHAO, Yuefei

IPC分类号： C07D233/88 ,  C07D239/22 ,  C07D401/06 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/14 ,  C07D495/10 ,  C07D401/10 ,  C07D417/10 ,  A61K31/513 ,  A61P25/28

CPC分类号： C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  C07D239/22 ,  C07D401/06 ,  C07D401/10 ,  C07D403/06 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/10 ,  C07D417/14 ,  C07D495/10

公开(公告)号：EP1699455B1

公开(公告)日：2013-05-08

申请号：EP04813947.1

申请日：2004-12-13

申请人： Merck Sharp & Dohme Corp. ,  Pharmacopeia, LLC

发明人： ZHU, Zhaoning ,  MCKITTRICK, Brian ,  SUN, Zhong-Yue ,  YE, Yuanzan, C. ,  STRICKLAND, Corey ,  SMITH, Elizabeth, M. ,  STAMFORD, Andrew ,  GREENLEE, William, J. ,  WU, Yusheng ,  ISERLOH, Ulrich ,  MAZZOLA, Robert ,  CALDWELL, John ,  CUMMING, Jared ,  WANG, Lingyan ,  GUO, Tao ,  LE, Thuy, X. H. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D. ,  VOIGT, Johannes H. ,  HUNTER, Rachael C.

IPC分类号： A61K31/4168 ,  A61K31/4178 ,  C07D233/88 ,  C07D239/22 ,  C07D271/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/06 ,  C07D403/10 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D407/14

CPC分类号： C07D233/88 ,  C07D235/02 ,  C07D239/22 ,  C07D271/07 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/10 ,  C07D405/12 ,  C07D405/14 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

公开(公告)号：EP2485591A1

公开(公告)日：2012-08-15

申请号：EP10822571.5

申请日：2010-10-06

申请人： Merck Sharp & Dohme Corp.

发明人： SCOTT, Jack, D. ,  STAMFORD, Andrew, W. ,  GILBERT, Eric, J. ,  CUMMING, Jared, N. ,  ISERLOH, Ulrich ,  WANG, Lingyan ,  LI, Wei

IPC分类号： A01N43/54 ,  A61K31/505

CPC分类号： C07D417/04 ,  C07D285/18 ,  C07D417/10

摘要： In its many embodiments, the present invention provides provides certain iminothiadiazine dioxide compounds, including compounds Formula (a) and include tautomers, solvates, prodrugs, esters, and deuterates thereof, and pharmaceutically acceptable salts of said compounds, tautomers, solvates, prodrugs, esters, and deuterates, wherein each of R
1 , R
2 , R
3 , R
4 , R
5 , R
9 , ring A, ring B, ring C, m, n, p, q, -L
1 -, -L
2 -,L
3 -, and L
4 - is selected independently and as defined herein. The compounds of the invention have, surprisingly and advantageously, improved solution stability. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed.

摘要翻译： 在其许多实施方案中，本发明提供了某些亚氨基噻二嗪二氧化物化合物，包括式（a）化合物，包括其互变异构体，溶剂化物，前药，酯和氘化物，以及所述化合物的可药用盐，互变异构体，溶剂化物，前药，酯 ，氘代，其中R 1，R 2，R 3，R 4，R 5，R 9，环A，环B，环C，m，n，p，q，-L 1 - ， - L 2 - ，L 3-和L 4-独立地选择并如本文所定义。 本发明的化合物令人惊讶且有利地具有改进的溶液稳定性。 还公开了包含一种或多种此类化合物（单独和与一种或多种其它活性剂组合）的药物组合物，以及它们的制备方法和用于治疗与淀粉样蛋白β（Aβ）蛋白相关的病理学，包括阿尔茨海默氏病。

公开(公告)号：EP2485591B1

公开(公告)日：2016-03-23

申请号：EP10822571.5

申请日：2010-10-06

申请人： Merck Sharp & Dohme Corp.

发明人： SCOTT, Jack, D. ,  STAMFORD, Andrew, W. ,  GILBERT, Eric, J. ,  CUMMING, Jared, N. ,  ISERLOH, Ulrich ,  WANG, Lingyan ,  LI, Wei

IPC分类号： C07D285/18 ,  C07D417/04 ,  C07D417/10 ,  A01N43/54 ,  A61K31/505 ,  A61P25/00

CPC分类号： C07D417/04 ,  C07D285/18 ,  C07D417/10

公开(公告)号：EP2908824A1

公开(公告)日：2015-08-26

申请号：EP13846341.9

申请日：2013-10-14

申请人： Merck Sharp & Dohme Corp.

发明人： GILBERT, Eric, J. ,  CUMMING, Jared, N. ,  STAMFORD, Andrew, W. ,  YU, Younong ,  SCOTT, Jack, D. ,  ISERLOH, Ulrich ,  WANG, Lingyan ,  CALDWELL, John, P.

IPC分类号： A61K31/54 ,  A01N43/00

CPC分类号： C07D417/14 ,  A61K31/549 ,  A61K45/06 ,  C07D417/10 ,  C07D495/04

摘要： In its many embodiments, the present invention provides provides certain iminothiazine dioxide compounds, including compounds Formula (I): (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein the middle ring (referred to herein as "ring B") of the tricyclic substituent is an optionally substituted 6-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

公开(公告)号：EP2919792A1

公开(公告)日：2015-09-23

申请号：EP13854794.8

申请日：2013-11-14

申请人： Merck Sharp & Dohme Corp.

发明人： BENNETT, Frank ,  HUANG, Yuhua ,  WANG, Lingyan ,  BOGEN, Stephane, L. ,  KEREKES, Angela, D. ,  GIRIJAVALLABHAN, Vinay M. ,  BUTORA, Gabor ,  TRUONG, Quang ,  DAVIES, Ian ,  WEBER, Anne E.

IPC分类号： A61K31/7068 ,  C07H19/02 ,  C07H19/10

CPC分类号： C07H19/10 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7068 ,  A61K31/7072 ,  A61K45/06 ,  C07H19/06 ,  C07H19/067 ,  C07H19/09 ,  C07H19/11

摘要： The present invention relates to 2′-Alkynyl Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2, R3 and R4 are as defined herein. The present invention also relates to compositions comprising at least one 2′-Alkynyl Substituted Nucleoside Derivative, and methods of using the 2′-Alkynyl Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

摘要翻译： 本发明涉及式（I）的2'-炔炔基取代的核苷衍生物及其药学上可接受的盐，其中B，X，R 1，R 2，R 3和R 4如本文所定义。 本发明还涉及包含至少一种2'-炔炔基取代的核苷衍生物的组合物，以及使用2'-炔基取代的核苷衍生物治疗或预防患者HCV感染的方法。

公开(公告)号：EP2908824B1

公开(公告)日：2018-05-02

申请号：EP13846341.9

申请日：2013-10-14

申请人： Merck Sharp & Dohme Corp.

发明人： GILBERT, Eric, J. ,  CUMMING, Jared, N. ,  STAMFORD, Andrew, W. ,  YU, Younong ,  SCOTT, Jack, D. ,  ISERLOH, Ulrich ,  WANG, Lingyan ,  CALDWELL, John, P.

IPC分类号： C07D417/14 ,  C07D417/10 ,  C07D495/04 ,  A61K31/549 ,  A61P25/28 ,  A61P25/16

CPC分类号： C07D417/14 ,  A61K31/549 ,  A61K45/06 ,  C07D417/10 ,  C07D495/04

摘要： In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein the middle ring (referred to herein as “ring B”) of the tricyclic substituent is an optionally substituted 6-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

公开(公告)号：EP1838304B1

公开(公告)日：2009-08-19

申请号：EP05766007.8

申请日：2005-06-09

申请人： Schering Corporation ,  Pharmacopeia, LLC

发明人： ZHU, Zhaoning ,  MCKITTRICK, Brian ,  SUN, Zhong-Yue ,  YE, Yuanzan ,  VOIGT, Johannes H. ,  STRICKLAND, Corey ,  SMITH, Elizabeth M. ,  STAMFORD, Andrew ,  GREENLEE, William J. ,  MAZZOLA, Robert ,  CALDWELL, John ,  CUMMING, Jared ,  WANG, Lingyan ,  WU, Yusheng ,  ISERLOH, Ulrich ,  GUO, Tao ,  LE, Thuy X.H. ,  SAIONZ, Kurt W. ,  BABU, Suresh D. ,  HUNTER, Rachael C. ,  MORRIS, Michelle L. ,  GU, Huizhong ,  QIAN, Gang ,  TADESSE, Dawit

IPC分类号： A61K31/4168 ,  A61K31/4178 ,  C07D233/46 ,  C07D233/88 ,  C07D239/22 ,  C07D271/06 ,  C07D273/00 ,  C07D401/10 ,  C07D403/06 ,  C07D403/12 ,  C07D407/10 ,  C07D409/04 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  A61P9/00 ,  A61P25/00

CPC分类号： C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/655 ,  A61K45/06 ,  C07D233/46 ,  C07D233/70 ,  C07D235/02 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D295/15 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D407/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  Y02A50/411

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(-S)-, -S(O)-, -S(O)2-, -C(-O)-, -O-, -C(R6)(R7)-, -N(R5)- or -C(-N(R5))-; X is -O-, -N(R5)- or -C(R6)(R7)-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(-O)- or -C(-NR5)-; U is a bond, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(-NR5)-, -(C(R6)(R7))b- or -N(R5)-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, U is not -S(O)-, -S(O)2-, -O-, or -N(R5)-; provided that when X is -N(R5)- and W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.