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：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：EP2288613A1

公开(公告)日：2011-03-02

申请号：EP09734237.2

申请日：2009-04-21

申请人： Schering Corporation

发明人： STAMFORD, Andrew, W. ,  ZHU, Zhaoning ,  MANDAL, Mihirbaran ,  WU, Yusheng ,  CUMMING, Jared, N. ,  LIU, Xiaoxiang ,  LI, Guoqing ,  ISERLOH, Ulrich

IPC分类号： C07D487/04 ,  A61P25/28 ,  A61K31/519

CPC分类号： C07D487/04

摘要： In its many embodiments, the present invention provides provides certain 2-imino-3-methyl pyrrolo pyrimidone compounds, including compounds Formula (II): and include tautomers, steroisomers, or pharmaceutically acceptable salts or solvates of said compounds, stereoisomers, or said tautomers, wherein R
2 , R
3 , R
4 , R
5 , R
6 , R
7 , R
8 , and R
9 are each selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds, and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's Disease, are also disclosed.

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.