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：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.