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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.
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公开(公告)号:US07763609B2
公开(公告)日:2010-07-27
申请号:US11710582
申请日:2007-02-23
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. 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. Voigt , 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: A61K31/535 , C07D273/04
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.
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公开(公告)号:US08242112B2
公开(公告)日:2012-08-14
申请号:US13108454
申请日:2011-05-16
申请人: Zhaoning Zhu , Brian McKittrick , Zhong-Yue Sun , Yuanzan C. Ye , Johannes H. Voigt , Corey Strickland , Elizabeth M. Smith , Andrew W. Stamford , William J. Greenlee , Robert D. Mazzola, Jr. , John P. Caldwell , Jared N. Cumming , Lingyan Wang , Yusheng Wu , Ulrich Iserloh , Tao Guo , Thuy X. H. Le , Kurt W. Saionz , Suresh D. Babu , Rachael C. Hunter , Michelle L. Morris , Huizhong Gu , Gang Qian , Dawit Tadesse
发明人: Zhaoning Zhu , Brian McKittrick , Zhong-Yue Sun , Yuanzan C. Ye , Johannes H. Voigt , Corey Strickland , Elizabeth M. Smith , Andrew W. Stamford , William J. Greenlee , Robert D. Mazzola, Jr. , John P. Caldwell , Jared N. Cumming , Lingyan Wang , Yusheng Wu , Ulrich Iserloh , Tao Guo , Thuy X. H. Le , Kurt W. Saionz , Suresh D. Babu , Rachael C. Hunter , Michelle L. Morris , Huizhong Gu , Gang Qian , Dawit Tadesse
IPC分类号: A61K31/535 , C07D273/04
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.
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24.
公开(公告)号:US20050119227A1
公开(公告)日:2005-06-02
申请号:US10910987
申请日:2004-08-04
申请人: Jared Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes Voigt , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas Hobbs , Thuy Le , Jeffrey Lowrie , Kurt Saionz , Suresh Babu
发明人: Jared Cumming , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes Voigt , Yusheng Wu , Ying Huang , Yan Xia , Samuel Chackalamannil , Tao Guo , Douglas Hobbs , Thuy Le , Jeffrey Lowrie , Kurt Saionz , Suresh Babu
IPC分类号: A61K31/55 , A61K31/553 , A61K31/554 , A61K31/675 , C07D207/09 , C07D211/26 , C07D217/18 , C07D241/04 , C07D243/08 , C07D401/06 , C07D403/12 , C07D403/14 , C07D413/06 , C07F9/38
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 R1 is 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, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.
摘要翻译: 公开了下式的化合物或其药学上可接受的盐或溶剂化物,其中R 1是R是-C(O)-N(R 27) > 28 SUP>)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变性疾病如阿尔茨海默病的方法。 还公开了治疗认知或神经变性疾病的药物组合物和方法,其包含式I化合物与除式I以外的β-分泌酶抑制剂,HMG-CoA还原酶抑制剂,γ-分泌酶抑制剂, 甾族抗炎剂,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。
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公开(公告)号:US20120231017A1
公开(公告)日:2012-09-13
申请号:US13415404
申请日:2012-03-08
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 , Xiaoiang Liu , Tao Guo , Thuy X. E. Le , Kurt W. Sainoz , 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 , Xiaoiang Liu , Tao Guo , Thuy X. E. Le , Kurt W. Sainoz , 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 , C07D239/70 , C07F5/02 , C07D403/10 , A61K31/513 , A61K31/506 , C07D409/04 , C07D409/14 , C07D401/04 , C07D405/14 , C07D417/14 , C07D417/04 , C07D413/14 , C07D413/10 , A61K31/5377 , A61P29/00 , A61P9/00 , A61P25/28 , A61P31/10 , A61P33/02 , C07D495/04 , A61P25/00 , A61P31/04 , C07D239/22
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.
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公开(公告)号:US08178513B2
公开(公告)日:2012-05-15
申请号:US12480391
申请日:2009-06-08
申请人: Zhaoning Zhu , Brian McKittrick , Zhong-Yue Sun , Yuanzan C. Ye , Johannes H. Voigt , Corey O. Strickland , Elizabeth M. Smith , Andrew W. Stamford , William J. Greenlee , Robert D. Mazzola, Jr. , John Caldwell , Jared N. Cumming , Lingyan Wang , Yusheng Wu , Ulrich Iserloh , Tao Guo , Thuy X. H. Le , Kurt W. Saionz , Suresh D. Babu , Rachael C. Hunter
发明人: Zhaoning Zhu , Brian McKittrick , Zhong-Yue Sun , Yuanzan C. Ye , Johannes H. Voigt , Corey O. Strickland , Elizabeth M. Smith , Andrew W. Stamford , William J. Greenlee , Robert D. Mazzola, Jr. , John Caldwell , Jared N. Cumming , Lingyan Wang , Yusheng Wu , Ulrich Iserloh , Tao Guo , Thuy X. H. Le , Kurt W. Saionz , Suresh D. Babu , Rachael C. Hunter
IPC分类号: A01N57/00 , A01N43/54 , A01N43/40 , A61K31/675 , A61K31/44 , A61K31/445 , C07D239/02 , C07D233/00 , C07D239/24 , C07D401/00
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, U, X, R1, R2, R3, and R4 are as defined herein, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of using such compounds to inhibit aspartyl protease and to treat a variety of disease or disorders, including 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 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W,U,X,R 1,R 2,R 3和R 4如本文所定义,并且药物组合物包含式I化合物 还公开了使用这些化合物抑制天冬氨酰蛋白酶和治疗各种疾病或病症(包括心血管疾病,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拮抗剂组合治疗认知或神经变性疾病的方法
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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.
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28.
公开(公告)号:US20050043290A1
公开(公告)日:2005-02-24
申请号:US10911030
申请日:2004-08-04
申请人: Jared Cumming , Ying Huang , Guoqing Li , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes Voigt , Yusheng Wu , Jianping Pan , Tao Guo , Douglas Hobbs , Thuy Le , Jeffrey Lowrie
发明人: Jared Cumming , Ying Huang , Guoqing Li , Ulrich Iserloh , Andrew Stamford , Corey Strickland , Johannes Voigt , Yusheng Wu , Jianping Pan , Tao Guo , Douglas Hobbs , Thuy Le , Jeffrey Lowrie
IPC分类号: C07D207/26 , C07D207/277 , C07D401/12 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/14 , A61K31/55 , C07D43/02
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 or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is X is —O—, —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, —SO2(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.
摘要翻译: 公开了下式的新化合物或其药学上可接受的盐或溶剂化物,其中R 1是X是-O - , - C(R 14)2 - 或-N(R) - ; Z是-C(R 14)2 - 或-N(R) - ; t为0,1,2或3; 每个R和R 2独立地是H,烷基,环烷基,环烷基烷基,芳基,杂芳基,杂环烷基,芳基烷基,杂芳基烷基,杂环烷基烷基,烯基或炔基; 每个R 14是H,烷基,烯基,炔基,卤素,-CN,卤代烷基,环烷基,环烷基烷基,芳基,杂芳基,杂环烷基,芳基烷基,杂芳基烷基,杂环烷基烷基,-OR 35,-N(R 24) )(R 25)或-SR 35; R 41是烷基,环烷基,-SO 2(烷基),-C(O) - 烷基,-C(O) - 环烷基或 - 烷基-NH-C(O)CH 3; 其余变量如本说明书中所定义。 还公开了包含式I化合物的药物组合物和用式I化合物治疗认知障碍或神经变性疾病的方法。还公开了药物组合物和治疗方法,其包含式I化合物与用于治疗认知或神经变性的其它药剂 疾病
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公开(公告)号:US08168641B2
公开(公告)日:2012-05-01
申请号:US11759336
申请日:2007-06-07
申请人: Yusheng Wu , Ulrich Iserloh , Jared N. Cumming , Xiaoxiang Liu , Robert D. Mazzola , Zhong-Yue Sun , Ying Huang , Andrew Stamford , Brian McKittrick , Zhaoning Zhu
发明人: Yusheng Wu , Ulrich Iserloh , Jared N. Cumming , Xiaoxiang Liu , Robert D. Mazzola , Zhong-Yue Sun , Ying Huang , Andrew Stamford , Brian McKittrick , Zhaoning Zhu
IPC分类号: C07D239/20 , C07D239/22 , A61K31/497 , A61K31/513 , A61K31/506 , A61P9/00 , A61P25/28 , A61P31/18 , C07D495/20 , A61K31/527
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,互变异构体或其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。
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公开(公告)号:US20120232064A1
公开(公告)日:2012-09-13
申请号:US13421396
申请日:2012-03-15
申请人: Yusheng Wu , Ulrich Iserloh , Jared N. Cumming , Xiaoxiang Liu , Robert D. Mazzola , Zhong-Yue Sun , Ying Huang , Andrew Stamford , Brian McKittrick , Zhaoning Zhu
发明人: Yusheng Wu , Ulrich Iserloh , Jared N. Cumming , Xiaoxiang Liu , Robert D. Mazzola , Zhong-Yue Sun , Ying Huang , Andrew Stamford , Brian McKittrick , Zhaoning Zhu
IPC分类号: A61K31/506 , C07D403/04 , A61K31/497 , A61P29/00 , A61K31/551 , A61P9/00 , A61P25/28 , C07D409/14 , C07D401/04
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,互变异构体或其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。
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