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1. 发明授权

US07612085B2 Sigma 2 receptor ligands and therapeutic uses therefor 有权
标题翻译： Sigma 2受体配体及其治疗用途
公开(公告)号：US07612085B2
公开(公告)日：2009-11-03
申请号：US11776533
申请日：2007-07-11
申请人： Robert H. Mach , Zhude Tu , Wenhua Chu , Suwanna Vangveravong , Richard Hotchkiss , William Hawkins , Rebecca Aft
发明人： Robert H. Mach , Zhude Tu , Wenhua Chu , Suwanna Vangveravong , Richard Hotchkiss , William Hawkins , Rebecca Aft
IPC分类号： A01N43/42 , A61K31/44 , C07D221/02
CPC分类号： C07D451/14 , C07D451/02
摘要： A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (σ1 and σ2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for σ2 versus σ1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the σ2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.
摘要翻译：公开了一系列N-取代的9-氮杂双环[3.3.1]壬烷-3-基苯基氨基甲酸酯类似物及其制备方法。描述了它们对西格玛（sigma1和sigma2）受体的亲和力。两种新化合物N-（9-（4-氨基丁基）-9-氮杂双环[3.3.1]壬-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯和N-（9- 6-氨基己基）-9-氮杂双环[3.3.1]壬-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯显示出对sigma2与σ1受体的高亲和力和选择性。所公开的化合物中有生物素化和荧光类似物。这些化合物可以作为sigma2受体的探针。此外，一些公开的化合物可以通过胱天蛋白酶依赖性和半胱天冬酶非依赖性机制诱导凋亡细胞死亡，并且对于治疗肿瘤是有效的。这些化合物可用作化学治疗剂或化学敏化剂，用于治疗各种实体瘤。

2. 发明申请

US20080161343A1 Sigma 2 Receptor Ligands and Therapeutic Uses Therefor 有权
标题翻译： Sigma 2受体配体及其治疗用途
公开(公告)号：US20080161343A1
公开(公告)日：2008-07-03
申请号：US11776533
申请日：2007-07-11
申请人： Robert H. Mach , Zhude Tu , Wenhua Chu , Suwanna Vangveravong , Richard Hotchkiss , William Hawkins , Rebecca Aft
发明人： Robert H. Mach , Zhude Tu , Wenhua Chu , Suwanna Vangveravong , Richard Hotchkiss , William Hawkins , Rebecca Aft
IPC分类号： A61K31/439 , C07D453/02 , C12N5/06 , A61P35/00
CPC分类号： C07D451/14 , C07D451/02
摘要： A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (σ1 and σ2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for σ2 versus σ1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the σ2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.
摘要翻译：公开了一系列N-取代的9-氮杂双环[3.3.1]壬烷-3-基苯基氨基甲酸酯类似物及其制备方法。描述了它们对西格玛（sigma1和sigma2）受体的亲和力。两种新化合物N-（9-（4-氨基丁基）-9-氮杂双环[3.3.1]壬-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯和N-（9- 6-氨基己基）-9-氮杂双环[3.3.1]壬-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯显示出对sigma2与σ1受体的高亲和力和选择性。所公开的化合物中有生物素化和荧光类似物。这些化合物可以作为sigma2受体的探针。此外，一些公开的化合物可以通过胱天蛋白酶依赖性和半胱天冬酶非依赖性机制诱导凋亡细胞死亡，并且对于治疗肿瘤是有效的。这些化合物可用作化学治疗剂或化学敏化剂，用于治疗各种实体瘤。

3. 发明授权

US08168650B2 Therapeutic uses of bicyclic ligands of sigma 2 receptor 有权
标题翻译： sigma2受体双环配体的治疗用途
公开(公告)号：US08168650B2
公开(公告)日：2012-05-01
申请号：US12543647
申请日：2009-08-19
申请人： Robert H. Mach , Richard Hotchkiss , William Hawkins , Rebecca Aft , Zhude Tu
发明人： Robert H. Mach , Richard Hotchkiss , William Hawkins , Rebecca Aft , Zhude Tu
IPC分类号： A01N43/42 , A61K31/44
CPC分类号： C07D451/14 , C07D451/02
摘要： A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (σ1 and σ2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for σ2 versus σ1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the σ2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.
摘要翻译：公开了一系列N-取代的9-氮杂双环[3.3.1]壬烷-3α-基苯基氨基甲酸酯类似物及其制备方法。描述了它们对西格玛（＆sgr。1和＆sgr; 2）受体的亲和力。两种新化合物N-（9-（4-氨基丁基）-9-氮杂双环[3.3.1]壬烷-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯和N-（9- 6-氨基己基）-9-氮杂双环[3.3.1]壬烷-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯显示出对于＆ 1受体。所公开的化合物中有生物素化和荧光类似物。这些化合物可以作为第二受体的探针。此外，一些公开的化合物可以通过胱天蛋白酶依赖性和半胱天冬酶非依赖性机制诱导凋亡细胞死亡，并且对于治疗肿瘤是有效的。该化合物可用作化学治疗剂或化学敏化剂，用于治疗各种实体瘤。

4. 发明申请

US20100048614A1 THERAPEUTIC USES OF BICYCLIC LIGANDS OF SIGMA 2 RECEPTOR 有权
标题翻译： SIGMA 2受体的双相配体的治疗用途
公开(公告)号：US20100048614A1
公开(公告)日：2010-02-25
申请号：US12543647
申请日：2009-08-19
申请人： Robert H. Mach , Richard Hotchkiss , William Hawkins , Rebecca Aft , Zhude Tu
发明人： Robert H. Mach , Richard Hotchkiss , William Hawkins , Rebecca Aft , Zhude Tu
IPC分类号： A61K31/439 , A61P35/00
CPC分类号： C07D451/14 , C07D451/02
摘要： A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (σ1 and σ2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for σ2 versus σ1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the σ2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.
摘要翻译：公开了一系列N-取代的9-氮杂双环[3.3.1]壬烷-3α-基苯基氨基甲酸酯类似物及其制备方法。描述了它们对西格玛（＆sgr。1和＆sgr; 2）受体的亲和力。两种新化合物N-（9-（4-氨基丁基）-9-氮杂双环[3.3.1]壬烷-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯和N-（9- 6-氨基己基）-9-氮杂双环[3.3.1]壬烷-3α-基）-N' - （2-甲氧基-5-甲基苯基）氨基甲酸酯显示出对于＆ 1受体。所公开的化合物中有生物素化和荧光类似物。这些化合物可以作为第二受体的探针。此外，一些公开的化合物可以通过胱天蛋白酶依赖性和半胱天冬酶非依赖性机制诱导凋亡细胞死亡，并且对于治疗肿瘤是有效的。这些化合物可用作化学治疗剂或化学敏化剂，用于治疗各种实体瘤。

5. 发明申请

US20060206218A1 Flexible Function Blocks 有权
标题翻译：灵活的功能块
公开(公告)号：US20060206218A1
公开(公告)日：2006-09-14
申请号：US11420704
申请日：2006-05-26
申请人： David Glanzer , Stephen Mitschke , William Hawkins , Michael von Le Suire , Sergio Tateishi
发明人： David Glanzer , Stephen Mitschke , William Hawkins , Michael von Le Suire , Sergio Tateishi
IPC分类号： G05B11/01 , G05B19/42
CPC分类号： G05B15/02 , G05B19/042 , G05B19/056 , G05B2219/13101 , G05B2219/13127 , G05B2219/15068 , G05B2219/23256 , G05B2219/25085 , G05B2219/25428 , G05B2219/31118 , H04L67/125 , H04L67/325 , H04L69/08
摘要： A new and improved control system architecture using a combination of standard function blocks and new flexible function blocks eliminates the need for expensive and difficult to maintain custom control software and special I/O gateways for discrete/hybrid/batch and PLC applications. The end user builds application-specific flexible function blocks by configuring the number and type of inputs and outputs, and the block algorithm. Flexible function blocks and gateway flexible function block interconnect and interoperate with each other and with standard function blocks in a distributed control architecture.
摘要翻译：使用标准功能块和新的灵活功能块组合的新型改进的控制系统架构无需昂贵且难以维护的定制控制软件和独立/混合/批量和PLC应用的特殊I / O网关。最终用户通过配置输入和输出的数量和类型以及块算法来构建应用程序特定的灵活功能块。灵活的功能块和网关灵活的功能块互连，并在分布式控制架构中与标准功能块互通。

6. 发明申请

US20080004727A1 Flexible function blocks 审中-公开
标题翻译：灵活的功能块
公开(公告)号：US20080004727A1
公开(公告)日：2008-01-03
申请号：US11900349
申请日：2007-09-10
申请人： David Glanzer , Stephen Mitschke , William Hawkins , Michael von Le Suire , Sergio Tateishi
发明人： David Glanzer , Stephen Mitschke , William Hawkins , Michael von Le Suire , Sergio Tateishi
IPC分类号： G05B15/02
CPC分类号： G05B15/02 , G05B19/042 , G05B19/056 , G05B2219/13101 , G05B2219/13127 , G05B2219/15068 , G05B2219/23256 , G05B2219/25085 , G05B2219/25428 , G05B2219/31118 , H04L67/125 , H04L67/325 , H04L69/08
摘要： A new and improved control system architecture using a combination of standard function blocks and new flexible function blocks eliminates the need for expensive and difficult to maintain custom control software and special I/O gateways for discrete/hybrid/batch and PLC applications. The end user builds application-specific flexible function blocks by configuring the number and type of inputs and outputs, and the block algorithm. Flexible function blocks and gateway flexible function block interconnect and interoperate with each other and with standard function blocks in a distributed control architecture.
摘要翻译：使用标准功能块和新的灵活功能块组合的新型改进的控制系统架构无需昂贵且难以维护的定制控制软件和独立/混合/批量和PLC应用的特殊I / O网关。最终用户通过配置输入和输出的数量和类型以及块算法来构建应用程序特定的灵活功能块。灵活的功能块和网关灵活的功能块互连，并在分布式控制架构中与标准功能块互通。

7. 发明申请

US20050240286A1 Block-oriented control system on high speed ethernet 审中-公开
公开(公告)号：US20050240286A1
公开(公告)日：2005-10-27
申请号：US10874455
申请日：2004-06-22
申请人： David Glanzer , Colin Corles , Steven Brodman , William Hawkins , Michael Hirst , Tony Kozlik , Lee Neitzel , Raymond Sawyer , Johan Tegnell
发明人： David Glanzer , Colin Corles , Steven Brodman , William Hawkins , Michael Hirst , Tony Kozlik , Lee Neitzel , Raymond Sawyer , Johan Tegnell
IPC分类号： G05B9/03 , G05B11/01 , G05B15/00 , G05B15/02 , G05B23/02 , G06F15/173 , H04L29/06
CPC分类号： G05B9/03 , G05B19/4185 , H04J3/0667 , H04L69/08 , H04L69/18 , Y02P90/18 , Y02P90/185
摘要： A distributed control system architecture (HSE) provides an open, interoperable solution optimized for integration of distributed control systems and other control devices in a high performance backbone, provides an open, interoperable solution that provides system time synchronization suitable for distributed control applications operable over a high performance backbone, and provides an open, interoperable solution that provides a fault tolerant high performance backbone as well as fault tolerant devices that are connected to the backbone. The distributed control system architecture comprises a High speed Ethernet Field Device Access (HSE FDA) Agent, which maps services of a distributed control system, e.g., a fieldbus System, to and from a standard, commercial off-the-shelf (COTS) Ethernet/Internet component. The distributed control system architecture also comprises a High speed Ethernet System Management Kernel (HSE SMK) that operates to keep a local time, and keeps the difference between the local time and a system time provided by a time server within a value specified by the time sync class. The local time is used to time stamp events so that event messages from devices may be correlated across the system. The distributed control system architecture further comprises a High speed Ethernet Local Area Network Redundancy Entity (HSE LRE) that provides redundancy transparent to the applications running on the system. The HSE LRE of each device periodically transmits a diagnostic message representing its view of the network to the other Devices on the system. Each device uses the diagnostic messages to maintain a Network Status Table (NST), which is used for fault detection and selection from a redundant pair of resources.

8. 发明申请

US20060281553A1 Creation of game elements using location information 审中-公开
标题翻译：使用位置信息创建游戏元素
公开(公告)号：US20060281553A1
公开(公告)日：2006-12-14
申请号：US11133814
申请日：2005-05-19
申请人： William Hawkins , Rick Marazzani
发明人： William Hawkins , Rick Marazzani
IPC分类号： A63F9/24
CPC分类号： G07F17/32 , G07F17/3223 , G07F17/323
摘要： Methods, systems, and machine-readable mediums are disclosed for creating game elements using location information. In one embodiment, at least one-machine readable medium has instructions stored thereon, which, when executed by a machine cause the machine to implement a game, to obtain information about a location of the machine, and to abstract the information into an element of the game.
摘要翻译：公开了使用位置信息来创建游戏元件的方法，系统和机器可读介质。在一个实施例中，至少一个机器可读介质具有存储在其上的指令，当由机器执行时，使得机器实现游戏，以获得关于机器位置的信息，并将该信息抽象成游戏。

9. 发明申请

US20060277273A1 Online travel system 审中-公开
标题翻译：在线旅游系统
公开(公告)号：US20060277273A1
公开(公告)日：2006-12-07
申请号：US11447651
申请日：2006-06-06
申请人： William Hawkins
发明人： William Hawkins
IPC分类号： G06F15/16
CPC分类号： H04L67/2838 , G06F16/954 , G06Q10/02 , H04L67/02 , H04L67/28
摘要： A unified web portal for potential travelers to find localized information specific to a particular geographic area and assist in direct booking of an itinerary with the selected establishments. The website is implemented on a web-enabled server maintained by a Manager, and includes a home page containing introductory travel information on the localized area and URL links to Business, Tourism, Lodging and Restaurants pages allowing the Client to specify travel categories for submission to a search engine to compile “best match” third-party URL links based on the categories, as we well as a Contact Us page displaying Manager contact info, an Upcoming Events page display a list of upcoming local events in the area. The layout of the web portal provides easy access to localized information specific to a particular geographic area, offers specific answers to questions that they might have, and provides a search engine that facilitates compilation of a personalized itinerary displayed with arrangements for direct booking through the respective establishments.
摘要翻译：一个统一的门户网站，可供潜在旅客查找特定地理区域的本地化信息，并协助与所选企业直接预订行程。该网站在由经理维护的网络服务的服务器上实现，并包括一个主页，其中包含本地化区域的入门旅游信息，以及指向“商业，旅游，住宿和餐馆”页面的URL链接，允许客户指定旅行类别以提交给搜索引擎根据类别编制“最佳匹配”第三方网址链接，以及显示经理联系人信息的“联系我们”页面，即将到来的活动页面将显示该地区即将到来的本地活动的列表。网络门户的布局可以轻松访问特定地理区域的本地化信息，提供他们可能拥有的问题的具体答案，并提供一个搜索引擎，便于汇编显示的个性化行程，并通过相应的方式进行直接预订机构。

10. 发明授权

US6005561A Interactive information delivery system 失效
标题翻译：互动信息传递系统
公开(公告)号：US6005561A
公开(公告)日：1999-12-21
申请号：US355755
申请日：1994-12-14
申请人： William Hawkins , Roderick Perkins , William Duvall
发明人： William Hawkins , Roderick Perkins , William Duvall
IPC分类号： H04N5/44 , H04N21/2343 , H04N21/235 , H04N21/433 , H04N21/435 , H04N21/442 , H04N21/45 , H04N21/4725 , H04N7/10 , H04H1/02
CPC分类号： H04N5/4401 , H04N21/23614 , H04N21/23617 , H04N21/2385 , H04N21/4332 , H04N21/4348 , H04N21/4349 , H04N21/4532 , H04N21/47 , H04N21/6118 , H04N21/47202 , H04N21/47211 , H04N21/47815 , H04N21/482
摘要： An information delivery system including a head end broadcasting a data stream of media objects, the head end being coupled to a broadcast television interface and at least one information service provider and including an encoder for encoding information in the media object is disclosed. The system may deliver and implement a programming guide delineating programming information available on the information delivery system in one or more media objects in the data stream in an encoded fashion by the encoder. A user terminal is coupled to the head-end and receives the media objects. The user terminal has an output and includes a decoder for the media objects. Also provided in one aspect is a user interface, at least partially stored in the user-terminal, which selects a user-defined subset of media objects for provision to the output of the user terminal. Further, an information navigation system for an information delivery system is provided. The navigation system functions with the electronic program guide and includes a user interface having a plurality of icon representations of various functions of the system, and including a broadcast television interface. The navigation system also includes a smart service navigator which interacts with the user interface and the electronic program guide to provide an output to the user.
摘要翻译：一种信息传递系统，包括广播媒体对象的数据流的头端，头端耦合到广播电视接口和至少一个信息服务提供者，并且包括用于对媒体对象中的信息进行编码的编码器。该系统可以编码器以编码的方式传送和实现编程指南，以编码方式描绘在数据流中的一个或多个媒体对象中的信息传递系统上可用的节目信息。用户终端耦合到头端并接收媒体对象。用户终端具有输出并且包括用于媒体对象的解码器。在一个方面还提供了至少部分地存储在用户终端中的用户界面，用户界面选择用户定义的媒体对象子集来提供用户终端的输出。此外，提供了一种用于信息传递系统的信息导航系统。该导航系统与电子节目指南一起工作，并且包括具有系统各种功能的多个图标表示的用户界面，并且包括广播电视接口。导航系统还包括智能服务导航器，其与用户界面和电子节目指南交互以向用户提供输出。

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