公开(公告)号：EP1896032A2

公开(公告)日：2008-03-12

申请号：EP06784808.5

申请日：2006-06-12

申请人： Schering Corporation ,  PHARMACOPEIA, INC.

发明人： STAMFORD, Andrew ,  LI, Guoqing ,  GREENLEE, William, J. ,  ZHU, Zhaoning ,  MCKITTRICK, Brian ,  MAZZOLA, Robert ,  HUANG, Ying ,  GUO, Tao ,  LE, Thuy X. H. ,  QIAN, Gang ,  SHAO, Yuefei

IPC分类号： A61K31/519 ,  A61K31/4035 ,  C07D487/04 ,  A61P33/00 ,  A61P25/28 ,  A61P9/00 ,  A61K31/18

CPC分类号： C07D471/04 ,  C07D209/44 ,  C07D487/04

摘要： Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Q, T, U, Y, Z, ring A and R, R1, R2, R3, R4, R5, R6, R6, R7 and R7' are as defined in the specification; pharmaceutical compositions comprising the compounds of formula I and the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases.

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.

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：EP1781625B1

公开(公告)日：2010-12-15

申请号：EP05773473.3

申请日：2005-07-20

申请人： Schering Corporation

发明人： HUANG, Ying ,  LI, Guoqing ,  STAMFORD, Andrew, W.

IPC分类号： C07D241/08 ,  A61K31/495

CPC分类号： C07D401/12 ,  C07D241/04 ,  C07D241/08 ,  C07D401/10 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

摘要： Disclosed are novel compounds of the formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4 and X 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 methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula (I) and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula (I), HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

公开(公告)号：EP1896477A1

公开(公告)日：2008-03-12

申请号：EP06784753.3

申请日：2006-06-12

申请人： Schering Corporation

发明人： ZHU, Zhaoning ,  MCKITTRICK, Brian ,  STAMFORD, Andrew, W. ,  HUANG, Ying ,  SMITH, Elizabeth, M.

IPC分类号： C07D487/04 ,  C07D498/04 ,  A61P9/00 ,  A61P25/00 ,  A61P25/28 ,  A61P31/18 ,  A61K31/395

CPC分类号： C07D487/04

摘要： Disclosed are compounds of the formula (I) Chemical formula should be inserted here as it appears on the abstract in paper form or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein U, W, R, R1, R2, R3 and R4 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.

摘要翻译： 公开的是式（I）化合物化学式应当以其在摘要中出现的纸形式或其立体异构体，互变异构体或药学上可接受的盐或溶剂化物插入本文，其中U，W，R，R1，R2，R3 和R4如说明书中所定义; 和包含式（I）化合物的药物组合物。 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拮抗剂联合治疗认知或神经退行性疾病的方法。

公开(公告)号：EP1896453B1

公开(公告)日：2009-12-02

申请号：EP06785168.3

申请日：2006-06-19

申请人： Schering Corporation

发明人： ASLANIAN, Robert G. ,  BERLIN, Michael Y. ,  HUANG, Ying ,  MCCORMICK, Kevin D. ,  MUTAHI, Mwangi W. ,  SHIH, Neng-Yang ,  TING, Pauline, C. ,  TOM, Wing, C. ,  ZHENG, Junying

IPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  A61P3/04 ,  A61P29/00 ,  A61P37/00

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14

摘要： Disclosed are compounds of the formula (I); or a pharmaceutically acceptable salt thereof, wherein: M1 and M3 are CH or N; M2 is CH, CF or N; Y is -C(=O)-, -C(=S)-, -(CH2)q-, -C(=NOR7)- or -SO1-2-; Z is a bond or optionally substituted alkylene or alkenylene; R1 is H, alkyl, alkenyl, or optionally substituted cycloalkyl, aryl, heteroaryl, heterocycloalkyl or a group of the formula (II); where ring A is a monoheteroaryl ring; R2 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome nonalcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma or cognition deficit disorders using said compounds, alone or in combination with other agents.

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：EP1237875B1

公开(公告)日：2005-08-31

申请号：EP00986362.2

申请日：2000-12-14

申请人： SCHERING CORPORATION

发明人： STAMFORD, Andrew, W. ,  BOYLE, Craig, D. ,  HUANG, Ying

IPC分类号： C07D233/54 ,  C07D413/10 ,  C07D401/10 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D401/06 ,  A61K31/415

CPC分类号： C07D233/64 ,  C07D233/88 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D417/12

公开(公告)号：EP1418913A1

公开(公告)日：2004-05-19

申请号：EP02752562.5

申请日：2002-07-24

申请人： Schering Corporation

发明人： STAMFORD, Andrew, W. ,  HUANG, Ying ,  LI, Guoqing

IPC分类号： A61K31/4409 ,  A61K31/444 ,  A61P3/04 ,  A61P3/10 ,  C07D211/58 ,  C07D211/96

CPC分类号： C07D409/14 ,  C07D211/58 ,  C07D211/96 ,  C07D401/12 ,  C07D401/14

摘要： The present invention discloses compounds of formula (I) which are novel receptor antagonists for NPY Y5 as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such NPY Y5 receptor antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.