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：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：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：EP1891021A1

公开(公告)日：2008-02-27

申请号：EP06772934.3

申请日：2006-06-12

申请人： Schering Corporation ,  PHARMACOPEIA, INC.

发明人： ZHU, Zhaoning ,  MCKITTRICK, Brian ,  STAMFORD, Andrew, W. ,  LE, Thuy, X.H. ,  GUO, Tao

IPC分类号： C07D239/70 ,  C07D491/10 ,  C07D495/10 ,  C07D471/10 ,  C07D487/10

CPC分类号： C07D471/10 ,  C07D239/70 ,  C07D487/10 ,  C07D491/10 ,  C07D495/10

摘要： Disclosed are certain substituted spiro iminopyrimidinones and other compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein U, W, A, R, R1, R2, R6a and R7, are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of using such compounds and compositions to inhibit aspartyl protease, and to treat a variety of disease and indications including (but not limited) to cardiovascular disease and cognitive and neurodegenerative disease. The compounds of the present invention are disclosed for use alone or in combination with one or more additional active ingredients such as cholinesterase inhibitors and a muscarinic m1 agonist and/or m2 antagonists.

摘要翻译： 本文公开了式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，其中U，W，A，R，R1，R2，R6a和R7如说明书中所定义; 以及包含式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拮抗剂组合治疗认知或神经退行性疾病的方法。

公开(公告)号：EP1896477B1

公开(公告)日：2010-09-22

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.

公开(公告)号：EP2061791A1

公开(公告)日：2009-05-27

申请号：EP07838173.8

申请日：2007-09-13

申请人： Schering Corporation

发明人： MCKITTRICK, Brian ,  SMITH, Elizabeth, M. ,  BENNETT, Chad, E. ,  HARRIS, Joel, M. ,  KISELGOF, Eugenia, Y. ,  KNUTSON, Chad, E. ,  KORAKAS, Peter ,  TULSHIAN, Deen ,  KIM, Hyunjin

IPC分类号： C07D471/08 ,  A61K31/438 ,  A61P3/00

CPC分类号： C07D471/08

摘要： Disclosed are compounds of the formula (I): and compounds of the formula (IIA): wherein R1, R2, R3, R4, R5, u and v are as defined herein. These compounds can be used in methods of treating pain (e.g., inflammatory pain, chronic pain, and neuropathic pain), methods of treating diabetes, and methods of inhibiting the absorption of cholesterol.

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：EP1943246A1

公开(公告)日：2008-07-16

申请号：EP06826991.9

申请日：2006-10-30

申请人： Schering Corporation

发明人： ZHU, Zhaoning ,  STAMFORD, Andrew, W. ,  MCKITTRICK, Brian

IPC分类号： C07D411/04 ,  A61K31/553

CPC分类号： C07D413/04 ,  C07F9/65848

摘要： Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein (W, 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：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：EP2300435A2

公开(公告)日：2011-03-30

申请号：EP09751268.5

申请日：2009-05-18

申请人： Schering Corporation

发明人： CLASBY, Martin, C. ,  GREENLEE, William, J. ,  CHACKALAMANNIL, Samuel ,  XIA, Yan ,  GAO, Xiaobang ,  CHELLIAH, Mariappan, V. ,  EAGEN, Keith, A. ,  VACCARO, Henry ,  CHAN, Tin-yau ,  MCKITTRICK, Brian ,  WANG, Li Yuan ,  PU, Haiyan

IPC分类号： C07D231/18 ,  C07D487/04 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04 ,  C07D413/14 ,  C07D403/14 ,  C07D401/14 ,  A61P7/02 ,  A61K31/416 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4152

CPC分类号： C07D487/04 ,  C07D231/18 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/04 ,  C07D413/14

摘要： The present invention relates to novel heterocyclic compounds of Formulae I-III: Formula I; [Chemical Formulas should be inserted here as they appears on abstract in.pdf form.] Formula II; Formula III as disclosed herein or a pharmaceutically acceptable salt, solvate, ester, prodrug or stereoisomer thereof. Also disclosed are pharmaceutical compositions comprising said compounds, and methods for using said compounds for treating or preventing a thromboembolic disorder.