公开(公告)号：EP1699455A1

公开(公告)日：2006-09-13

申请号：EP04813947.1

申请日：2004-12-13

申请人： SCHERING CORPORATION ,  Pharmacopeia Drug Discovery, Inc.

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

摘要： Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof. 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.

公开(公告)号：EP1660443A2

公开(公告)日：2006-05-31

申请号：EP04779938.2

申请日：2004-08-04

申请人： SCHERING CORPORATION ,  Pharmacopeia Drug Discovery, Inc.

发明人： CUMMING, Jared, N. ,  ISERLOH, Ulrich ,  STAMFORD, Andrew ,  STRICKLAND, Corey ,  VOIGT, Johannes, H. ,  WU, Yusheng ,  HUANG, Ying ,  XIA, Yan ,  CHACKALAMANNIL, Samuel ,  GUO, Tao ,  HOBBS, Douglas, W. ,  LE, Thuy, X., H. ,  LOWRIE, Jeffrey, F. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D.

IPC分类号： C07D201/00

CPC分类号： C07D243/08 ,  C07D205/04 ,  C07D207/08 ,  C07D207/09 ,  C07D207/12 ,  C07D207/26 ,  C07D209/52 ,  C07D211/26 ,  C07D211/46 ,  C07D217/18 ,  C07D233/32 ,  C07D241/04 ,  C07D241/08 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D409/06 ,  C07D409/12 ,  C07D413/06

摘要： Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R is-C(O)-N(R27 )(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer’s disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, and N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

摘要翻译： 公开了下式化合物或其药学上可接受的盐或溶剂化物，其中R为-C（O）-N（R 27）（R 28）或其余变量如说明书中所定义。 还公开了包含式I化合物的药物组合物。还公开了治疗认知或神经退行性疾病例如阿尔茨海默氏病的方法。 还公开了治疗认知或神经退行性疾病的药物组合物和方法，其包含式I化合物与不同于式I的那些β-分泌酶抑制剂，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂， 类固醇抗炎剂和N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂或抗淀粉样蛋白抗体。

公开(公告)号：EP1660443B1

公开(公告)日：2009-03-04

申请号：EP04779938.2

申请日：2004-08-04

申请人： Schering Corporation ,  Pharmacopeia Drug Discovery, Inc.

发明人： CUMMING, Jared, N. ,  ISERLOH, Ulrich ,  STAMFORD, Andrew ,  STRICKLAND, Corey ,  VOIGT, Johannes, H. ,  WU, Yusheng ,  HUANG, Ying ,  XIA, Yan ,  CHACKALAMANNIL, Samuel ,  GUO, Tao ,  HOBBS, Douglas, W. ,  LE, Thuy, X., H. ,  LOWRIE, Jeffrey, F. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D.

IPC分类号： C07D201/00

CPC分类号： C07D243/08 ,  C07D205/04 ,  C07D207/08 ,  C07D207/09 ,  C07D207/12 ,  C07D207/26 ,  C07D209/52 ,  C07D211/26 ,  C07D211/46 ,  C07D217/18 ,  C07D233/32 ,  C07D241/04 ,  C07D241/08 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D409/06 ,  C07D409/12 ,  C07D413/06

摘要： Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R is-C(O)-N(R27 )(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer’s disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, and N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

公开(公告)号：EP1660447A1

公开(公告)日：2006-05-31

申请号：EP04780561.9

申请日：2004-08-04

申请人： SCHERING CORPORATION ,  Pharmacopeia Drug Discovery, Inc.

发明人： CUMMING, Jared, N. ,  HUANG, Ying ,  LI, Guoqing ,  ISERLOH, Ulrich ,  STAMFORD, Andrew ,  STRICKLAND, Corey ,  VOIGT, Johannes, H. ,  WU, Yusheng ,  PAN, Jianping ,  GUO, Tao ,  HOBBS, Douglas, W. ,  LE, Thuy, X., H. ,  LOWRIE, Jeffrey, F.

IPC分类号： C07D207/26 ,  C07D413/12 ,  C07D401/12 ,  C07D403/12 ,  C07D401/14 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14 ,  C07D405/06 ,  C07D409/06

CPC分类号： C04B35/632 ,  C07D207/277 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is formula (I) X is -0-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24)(R25) or -SR35; R41 is alkyl, cycloalkyl, -S02(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula (I). Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

公开(公告)号：EP2032542A2

公开(公告)日：2009-03-11

申请号：EP07795971.6

申请日：2007-06-07

申请人： Schering Corporation

发明人： WU, Yusheng ,  ISERLOH, Ulrich ,  CUMMING, Jared ,  LIU, Xiaoxiang ,  MAZZOLA, Robert, D. ,  SUN, Zhong-Yue ,  HUANG, Ying ,  STAMFORD, Andrew ,  MCKITTRICK, Brian ,  ZHU, Zhaoning

IPC分类号： C07D239/20 ,  C07D401/04 ,  C07D401/10 ,  C07D403/04 ,  C07D405/04 ,  C07D409/14 ,  C07D411/04 ,  C07D417/14 ,  C07D495/20 ,  A61K31/513 ,  A61P25/28

CPC分类号： C07D239/20 ,  C07D401/04 ,  C07D401/10 ,  C07D403/04 ,  C07D405/04 ,  C07D409/14 ,  C07D411/04 ,  C07D417/04 ,  C07D417/14 ,  C07D495/20

摘要： Disclosed are compounds of formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, U, W, X, R1, R2, R6, R7, R30 and R31 are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. 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 m1 agonist or m2 antagonist.

摘要翻译： 公开了式（I）化合物或其立体异构体，互变异构体或药学上可接受的盐或溶剂合物，U，W，X，R 1，R 2，R 6，R 7，R 30和R 31如上文在说明书中所述。 还公开了抑制天冬氨酰蛋白酶的方法，特别是治疗心血管疾病，认知和神经退行性疾病的方法。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱m1激动剂或m2拮抗剂组合治疗认知或神经退行性疾病的方法。

公开(公告)号：EP1660447B1

公开(公告)日：2008-07-30

申请号：EP04780561.9

申请日：2004-08-04

申请人： Schering Corporation ,  PHARMACOPEIA, INC.

发明人： CUMMING, Jared, N. ,  HUANG, Ying ,  LI, Guoqing ,  ISERLOH, Ulrich ,  STAMFORD, Andrew ,  STRICKLAND, Corey ,  VOIGT, Johannes, H. ,  WU, Yusheng ,  PAN, Jianping ,  GUO, Tao ,  HOBBS, Douglas, W. ,  LE, Thuy, X., H. ,  LOWRIE, Jeffrey, F.

IPC分类号： C07D207/26 ,  C07D413/12 ,  C07D401/12 ,  C07D403/12 ,  C07D401/14 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14 ,  C07D405/06 ,  C07D409/06

CPC分类号： C04B35/632 ,  C07D207/277 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is formula (I) X is -0-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24)(R25) or -SR35; R41 is alkyl, cycloalkyl, -S02(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula (I). Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

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.

公开(公告)号：EP1902057A1

公开(公告)日：2008-03-26

申请号：EP06772846.9

申请日：2006-06-12

申请人： Schering Corporation

发明人： ISERLOH, Ulrich ,  ZHU, Zhaoning ,  STAMFORD, Andrew ,  VOIGT, Johannes, H.

IPC分类号： C07D487/08 ,  A61K31/395 ,  A61P9/00 ,  A61P25/00 ,  A61P31/00 ,  A61P33/00

CPC分类号： C07D487/08

摘要： ABSTRACT Disclosed are compounds of the formula I (Chemical formula should be inserted here as it appears on abstract in final form) or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R1, R2, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 , R17 and R18 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. 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 m1 agonist or m2 antagonist.

公开(公告)号：EP1838304A2

公开(公告)日：2007-10-03

申请号：EP05766007.8

申请日：2005-06-09

申请人： Schering Corporation ,  PHARMACOPEIA, INC.

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.

公开(公告)号：EP2097387A2

公开(公告)日：2009-09-09

申请号：EP08714220.4

申请日：2008-02-20

申请人： Schering Corporation ,  Pharmacopeia, Inc.

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

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 m1 agonist or m2 antagonist.