公开(公告)号：US08623867B2

公开(公告)日：2014-01-07

申请号：US13610162

申请日：2012-09-11

申请人： Jared N. Cumming ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voight ,  Yusheng Wu ,  Ying Huang ,  Yan Xia ,  Samuel Chackalamannil ,  Tao Guo ,  Douglas W. Hobbs ,  Thuy X. H. Le ,  Jeffrey H. Lowrie ,  Kurt W. Saionz ,  Suresh D. Babu

发明人： Jared N. Cumming ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voight ,  Yusheng Wu ,  Ying Huang ,  Yan Xia ,  Samuel Chackalamannil ,  Tao Guo ,  Douglas W. Hobbs ,  Thuy X. H. Le ,  Jeffrey H. Lowrie ,  Kurt W. Saionz ,  Suresh D. Babu

IPC分类号： A61K31/445 ,  A61K31/4458 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/5377 ,  C07D295/027 ,  C07D401/06 ,  C07D401/12 ,  C07D413/12

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R1是R是-C（O）-N（R27）（R28），或其余的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。

公开(公告)号：US20130004518A1

公开(公告)日：2013-01-03

申请号：US13610162

申请日：2012-09-11

申请人： Jared N. Cumming ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voight ,  Yusheng Wu ,  Ying Huang ,  Yan Xia ,  Samuel Chackalamannil ,  Tao Guo ,  Douglas W. Hobbs ,  Thuy X.H. Le ,  Jeffrey F. Lowrie ,  Kurt W. Saionz ,  Suresh D. Babu

发明人： Jared N. Cumming ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voight ,  Yusheng Wu ,  Ying Huang ,  Yan Xia ,  Samuel Chackalamannil ,  Tao Guo ,  Douglas W. Hobbs ,  Thuy X.H. Le ,  Jeffrey F. Lowrie ,  Kurt W. Saionz ,  Suresh D. Babu

IPC分类号： C07D207/09 ,  C07F9/572 ,  A61K31/675 ,  C07D217/18 ,  A61K31/472 ,  C07F9/62 ,  C07D207/12 ,  A61K31/4025 ,  C07D401/14 ,  A61K31/4439 ,  C07D205/04 ,  A61K31/397 ,  C07D211/26 ,  A61K31/4458 ,  C07D211/46 ,  A61K31/445 ,  C07D413/12 ,  A61K31/5377 ,  C07D401/12 ,  A61K31/454 ,  C07D401/04 ,  A61K31/451 ,  A61K31/4545 ,  C07D241/08 ,  A61K31/495 ,  C07D403/12 ,  A61K31/496 ,  C07D241/24 ,  C07D413/06 ,  C07D243/08 ,  A61K31/551 ,  A61K39/395 ,  A61K31/5415 ,  A61K31/505 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61K31/40

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, whereinR1 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R1是R是-C（O）-N（R27）（R28），或其余的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以外的分泌抑制剂抑制剂，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂，非 - 甾族抗炎药，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：US20110218194A1

公开(公告)日：2011-09-08

申请号：US13108454

申请日：2011-05-16

申请人： Zhaoning Zhu ,  Brian A. Mckittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X. H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachel C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

发明人： Zhaoning Zhu ,  Brian A. Mckittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X. H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachel C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

IPC分类号： A61K31/5395 ,  C07D273/04 ,  C07D413/10 ,  A61P9/00 ,  A61P33/02 ,  A61P31/10 ,  A61P25/28 ,  A61P25/00

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：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：US20140057910A1

公开(公告)日：2014-02-27

申请号：US13402521

申请日：2012-02-22

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert Mazzola ,  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. Voight ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert Mazzola ,  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： A61K31/5377 ,  A61K31/4168 ,  C07D405/06 ,  A61K31/4178 ,  C07D401/04 ,  A61K45/06 ,  A61K31/454 ,  C07D409/06 ,  C07D401/06 ,  C07D295/15 ,  A61K31/4184 ,  C07D233/88 ,  A61K31/4439

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.

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为键，-C（= S） - ， - S（O） - ， - S（O） -C（= O） - ， - O - ， - C（R6）（R7） - ， - N（R5） - 或-C（= N（R5） X是-O - ， - N（R 5） - 或-C（R 6）（R 7） - ; 条件是当X是-O-时，U不是-O-，-S（O） - ， - S（O）2 - ， - C（= O） - 或-C（= NR5） - ; U是一个键，-S（O） - ， - S（O）2 - ， - C（O） - ， - O - ， - O（OR） （C（R6）（R7））b-或-N（R5） - ; 其中b为1或2; 条件是当W是-S（O） - ， - S（O）2 - ， - O-或-N（R 5） - 时，U不是-S（O） - ， - S（O） -O-或-N（R 5） - ; 条件是当X为-N（R5） - 且W为-S（O） - ， - S（O）2 - ， - O-或-N（R5） - 时，则U不为键; 并且R1，R2，R3，R4，R5，R6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，认知和神经变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拮抗剂组合来治疗认知或神经变性疾病的方法。

公开(公告)号：US08691831B2

公开(公告)日：2014-04-08

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. Voight ,  Corey O. 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 ,  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 W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  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： A01N43/54 ,  A61K31/505

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 I 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I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：US08829036B2

公开(公告)日：2014-09-09

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 W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoiang 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 W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoiang 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： A61K31/4168 ,  A61K31/4178 ,  C07D403/06 ,  C07D233/88

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.

公开(公告)号：US08691833B2

公开(公告)日：2014-04-08

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. Voight ,  Corey O. 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 ,  Xiaoiang 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 W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoiang 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： A01N43/54 ,  A61K31/505 ,  C07D239/02

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.

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。