公开(公告)号：US20070060575A1

公开(公告)日：2007-03-15

申请号：US11451541

申请日：2006-06-12

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Andrew Stamford ,  William Greenlee ,  Xiaoxiang Liu ,  Mihirbaran Mandal ,  Johannes Voigt ,  Corey Strickland

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Andrew Stamford ,  William Greenlee ,  Xiaoxiang Liu ,  Mihirbaran Mandal ,  Johannes Voigt ,  Corey Strickland

IPC分类号： A61K31/5513 ,  A61K31/53 ,  A61K31/519 ,  C07D487/02

CPC分类号： C07D487/04

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein j, k, U, W, R, R1, R2, R3, R4, R6, R7 and R7a 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，互变异构体或其药学上可接受的盐或溶剂化物，其中j，k，U，W，R，R 1，R 2， R 3，R 4，R 4，R 6，R 7和R 7a， >如说明书中所述。 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，认知和神经变性疾病的方法。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱m 1激动剂或m 2 H 2拮抗剂组合治疗认知或神经变性疾病的方法。

公开(公告)号：US20080200445A1

公开(公告)日：2008-08-21

申请号：US11710582

申请日：2007-02-23

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

IPC分类号： A61K31/506 ,  A61K31/4178 ,  A61K31/4245 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/541 ,  A61P31/00 ,  C07D233/02 ,  C07D271/00 ,  C07D413/14 ,  C07D409/14 ,  C07D409/04 ,  C07D403/06 ,  C07D401/14 ,  C07D401/12 ,  C07D401/10 ,  C07D401/06 ,  C07D239/04 ,  A61P9/00 ,  A61P25/00 ,  A61K31/5377 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/498

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 1. 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：US20070072852A1

公开(公告)日：2007-03-29

申请号：US11010772

申请日：2004-12-13

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter

IPC分类号： A61K31/549 ,  A61K31/5395 ,  A61K31/513

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：US20060111370A1

公开(公告)日：2006-05-25

申请号：US11149027

申请日：2005-06-09

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

IPC分类号： A61K31/519 ,  A61K31/497 ,  A61K31/513 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4245 ,  C07D413/02 ,  C07D403/02

CPC分类号： C07D233/46 ,  C07D233/70 ,  C07D233/88 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D401/04 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/10 ,  C07D409/04 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06

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：US07868000B2

公开(公告)日：2011-01-11

申请号：US11451541

申请日：2006-06-12

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Andrew Stamford ,  William J. Greenlee ,  Xiaoxiang Liu ,  Mihirbaran Mandal ,  Johannes H. Voigt ,  Corey O. Strickland

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Andrew Stamford ,  William J. Greenlee ,  Xiaoxiang Liu ,  Mihirbaran Mandal ,  Johannes H. Voigt ,  Corey O. Strickland

IPC分类号： A61K31/55 ,  A61K31/53 ,  A61K31/519 ,  A01N43/62 ,  A01N43/64 ,  A01N43/90 ,  C07D253/08 ,  C07D487/00 ,  C07D491/00 ,  C07D513/00 ,  C07D515/00

CPC分类号： C07D487/04

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein j, k, U, W, R, R1, R2, R3, R4, R6, R7 and R7a 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，互变异构体或其药学上可接受的盐或溶剂合物，其中j，k，U，W，R，R1，R2，R3，R4，R6，R7和R7a如上所述 规格。 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，认知和神经变性疾病的方法。 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变性疾病的方法。

公开(公告)号：US08450331B2

公开(公告)日：2013-05-28

申请号：US12988464

申请日：2009-04-21

申请人： Zhaoning Zhu ,  Andrew Stamford ,  Mihirbaran Mandal ,  Xiaoxiang Liu

发明人： Zhaoning Zhu ,  Andrew Stamford ,  Mihirbaran Mandal ,  Xiaoxiang Liu

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/28 ,  A61P3/10

CPC分类号： C07D487/04

摘要： In its many embodiments, the present invention provides certain thiophenyl-substituted 2-imino-3-methyl pyrrolo pyrimidone compounds, including compounds (or tautomers or a pharmaceutically acceptable salts thereof) having the structural Formula (III): wherein R2, R3, R4, R5, R6, R7, R8, and R9 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.

摘要翻译： 在其许多实施方案中，本发明提供了具有结构式（III）的化合物（或其互变异构体或其药学上可接受的盐）的某些噻吩基取代的2-亚氨基-3-甲基吡咯烷酮化合物：其中R2，R3，R4 ，R 5，R 6，R 7，R 8和R 9各自独立地并如本文所定义。 还公开了包含一种或多种这样的化合物的药物组合物，及其制备和用于治疗与包括阿尔茨海默病在内的淀粉样蛋白β（Abeta）蛋白相关的病理学的方法。

公开(公告)号：US20100069406A1

公开(公告)日：2010-03-18

申请号：US12517744

申请日：2007-12-10

申请人： Zhaoning Zhu ,  Andrew Stamford ,  Mihirbaran Mandal ,  Xiaoxiang Liu

发明人： Zhaoning Zhu ,  Andrew Stamford ,  Mihirbaran Mandal ,  Xiaoxiang Liu

IPC分类号： A61K31/5025 ,  C07D471/22 ,  A61P25/28

CPC分类号： C07D471/14 ,  C07D239/95

摘要： Disclosed are compounds of formula I (Chemical formula should be inserted here as it appears on abstract in paper form) Formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4, R14, V, W, X, Y, Z, p, and ring A are as described 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的化合物（化学式应该在此插入，如其以纸的形式呈现）式I或其立体异构体，互变异构体或其药学上可接受的盐或溶剂化物，其中R1，R2，R3，R4，R14，V ，W，X，Y，Z，p和环A如说明书中所述。 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，认知和神经变性疾病的方法。 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变性疾病的方法。

公开(公告)号：US08093254B2

公开(公告)日：2012-01-10

申请号：US12517744

申请日：2007-12-10

申请人： Zhaoning Zhu ,  Andrew Stamford ,  Mihirbaran Mandal ,  Xiaoxiang Liu

发明人： Zhaoning Zhu ,  Andrew Stamford ,  Mihirbaran Mandal ,  Xiaoxiang Liu

IPC分类号： A01N43/54 ,  A61K31/505 ,  C07D239/70 ,  C07D471/00 ,  C07D471/22 ,  C07D487/00 ,  C07D491/00

CPC分类号： C07D471/14 ,  C07D239/95

摘要： Disclosed are compounds of formula I (Chemical formula should be inserted here as it appears on abstract in paper form) Formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4, R14, V, W, X, Y, Z, p, and ring A are as described 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的化合物（化学式应该在此插入，如其以纸的形式呈现）式I或其立体异构体，互变异构体或其药学上可接受的盐或溶剂化物，其中R1，R2，R3，R4，R14，V ，W，X，Y，Z，p和环A如说明书中所述。 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，认知和神经变性疾病的方法。 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变性疾病的方法。

公开(公告)号：US20120276118A1

公开(公告)日：2012-11-01

申请号：US13420007

申请日：2012-03-14

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert D. Mazzola ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy X.E. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey A. Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert D. Mazzola ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy X.E. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey A. Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

IPC分类号： A61K39/395

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 each variable in Formula 1 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods 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.

摘要翻译： 公开了式I化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂化物，其中式1中的每个变量如说明书中所定义; 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，以及抑制人类免疫缺陷病毒，plasmepins，组织蛋白酶D和 原生动物酶。 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变性疾病的方法。

公开(公告)号：US20120231018A1

公开(公告)日：2012-09-13

申请号：US13416140

申请日：2012-03-09

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voigt ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert D. Mozzola ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy X. E. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey A. Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voigt ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert D. Mozzola ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy X. E. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey A. Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

IPC分类号： A61K31/513 ,  A61P25/28 ,  A61P31/10 ,  A61P25/00 ,  A61P29/00 ,  A61K39/395 ,  A61P31/04 ,  A61P9/00 ,  A61P33/02

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 each variable in Formula 1 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods 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.