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1. 发明申请

US20060111370A1 Heterocyclic aspartyl protease inhibitors 有权
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.

2. 发明申请

US20080200445A1 Heterocyclic aspartyl protease inhibitors 有权
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.

3. 发明申请

US20070072852A1 Heterocyclic aspartyl protease inhibitors 有权
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.

4. 发明申请

US20050119227A1 Cyclic amine bace-1 inhibitors having a benzamide substituent 有权
标题翻译：具有苯甲酰胺取代基的环胺类Bace-1抑制剂
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 ）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。

5. 发明申请

US20050043290A1 Cyclic amine BACE-1 inhibitors having a heterocyclic substituent 有权
标题翻译：具有杂环取代基的环胺BACE-1抑制剂
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

6. 发明申请

US20060287294A1 Aspartyl protease inhibitors 有权
标题翻译：天冬氨酰蛋白酶抑制剂
公开(公告)号：US20060287294A1
公开(公告)日：2006-12-21
申请号：US11451195
申请日：2006-06-12
申请人： Zhaoning Zhu , Brian McKittrick , Andrew Stamford , Tao Guo , Thuy Le
发明人： Zhaoning Zhu , Brian McKittrick , Andrew Stamford , Tao Guo , Thuy Le
IPC分类号： A61K31/554 , A61K31/553 , A61K31/551 , C07D285/36 , C07D243/10 , C07D223/14
CPC分类号： C07D471/10 , C07D239/70 , C07D487/10 , C07D491/10 , C07D495/10
摘要： Disclosed are 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 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U，W，A，R，R 1，R 2， R 6a和R 7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。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。

7. 发明授权

US08428861B1 Wrong way detection system 有权
标题翻译：错误的方式检测系统
公开(公告)号：US08428861B1
公开(公告)日：2013-04-23
申请号：US12797287
申请日：2010-06-09
申请人： Ray Williams , Thuy Le , Tracy Marks
发明人： Ray Williams , Thuy Le , Tracy Marks
IPC分类号： G06F17/10
CPC分类号： G08G1/056 , G08G1/095 , G08G1/164
摘要： The Wrong Way Detection System includes detection stations deployed at each egress point along a tollway in addition to various locations along the tollway's mainline. The detection hardware communicates preferably via fiber optic network to a customized software platform housed at a centrally located Incident Management Center (IMC) of the system, where each site is monitored 24/7 in real time for wrong way vehicles. Once a vehicle is detected, operators at the IMC are able to immediately dispatch law enforcement officers and monitor the vehicle's whereabouts via CCTV cameras.
摘要翻译：错误检测系统包括沿着收费站的每个出口点部署的检测站，以及沿着收费站主干线的各个位置。检测硬件优选地通过光纤网络传送到安装在系统的位于中心位置的事故管理中心（IMC）处的定制软件平台，其中每个站点被实时地全天候监控用于错误的方式车辆。一旦检测到车辆，IMC的操作人员可以立即派出执法人员并通过闭路电视摄像机监控车辆的下落。

8. 发明授权

US06783367B1 Method and system for providing a global product services electronic laboratory 有权
标题翻译：提供全球产品服务电子实验室的方法和系统
公开(公告)号：US06783367B1
公开(公告)日：2004-08-31
申请号：US10079227
申请日：2002-02-19
申请人： Geefu Wang , Douglas Hong , Chun Wu , Thuy Le , Yu-Tien Chi
发明人： Geefu Wang , Douglas Hong , Chun Wu , Thuy Le , Yu-Tien Chi
IPC分类号： G09B2300
CPC分类号： G09B5/00 , G06F19/00 , G06Q50/22
摘要： One embodiment of the present invention provides a global product services electronic laboratory (E-Lab). For example, the E-Lab may be an on-line virtual laboratory for company employees and/or field engineers for learning how to implement new technology products via actual “hands-on” configurations and troubleshooting. Specifically, the E-Lab of the present embodiment enables an authorized user to utilize a computing device to remotely access the E-Lab via the Internet, a company network or a dial-up connection. Once communicatively coupled to the E-Lab, the user is provided a variety of different topics and categories associated with the products and/or equipment labs currently available within the E-Lab. After selecting one of the topics or categories, the user may be provided more specific information regarding tutorials and/or troubleshooting corresponding to the selected lab equipment. Additionally, the user is able to directly interact with the actual equipment on-line thereby having a “hands-on” learning experience.
摘要翻译：本发明的一个实施例提供了一种全球产品服务电子实验室（E-Lab）。例如，电子实验室可能是公司员工和/或现场工程师的在线虚拟实验室，用于通过实际的“动手”配置和故障排除来学习如何实施新技术产品。具体地，本实施例的电子实验室使得授权用户能够利用计算设备经由因特网，公司网络或拨号连接远程访问E-Lab。一旦通信耦合到E-Lab，用户就可以获得与目前在E-Lab中可用的产品和/或设备实验室相关的各种不同的主题和类别。在选择其中一个主题或类别之后，可以向用户提供关于与所选择的实验室设备相对应的教程和/或故障排除的更具体的信息。此外，用户能够直接与实际设备进行在线交互，从而具有“动手”的学习体验。

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