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41. 发明授权

US5112595A 99MTC(III) myocardial imaging agents and method of use 失效
标题翻译： 99MTC（III）心肌成像剂及使用方法
公开(公告)号：US5112595A
公开(公告)日：1992-05-12
申请号：US632285
申请日：1990-12-21
申请人： Steven R. Woulfe , Edward A. Deutsch , Mary M. Dyszlewski , William L. Neumann
发明人： Steven R. Woulfe , Edward A. Deutsch , Mary M. Dyszlewski , William L. Neumann
IPC分类号： A61K51/04 , C07B59/00
CPC分类号： C07B59/004 , A61K51/0478 , A61K2123/00
摘要： A myocardial imaging agent for use in humans comprising a Tc(III) complex ligated in a planar position by a tetradentate ligand having incorporated therein four hard atoms and two furanone rings and in the axial positions by phosphines containing dioxanyl or ether moieties. The agent exhibits improved biodistribution, improved labeling and extremely rapid blood clearance following administration to a human. The agent has high myocardial uptake accompanied with exceptionally rapid hepatobilary clearance and extensive renal clearance to give sufficiently high heart/liver and heart/lung ratio that provide nearly ideal myocardial images in humans.
摘要翻译：一种用于人的心肌显像剂，其包含通过四齿配体连接在平面位置的Tc（III）复合物，其四个硬原子和两个呋喃酮环，并且在轴向位置由含有二烷基或醚部分的膦。该药物在施用于人后表现出改善的生物分布，改进的标记和极快的血液清除。该药物具有高心肌摄取，伴随着非常快速的肝胆清除和广泛的肾清除，以提供足够高的心/肝和心/肺比，其在人体中提供几乎理想的心肌图像。

42. 发明授权

US5105014A Synthesis of vicinal diamines 失效
标题翻译：邻氨基二胺的合成
公开(公告)号：US5105014A
公开(公告)日：1992-04-14
申请号：US741012
申请日：1991-08-06
申请人： William L. Neumann
发明人： William L. Neumann
IPC分类号： C07C209/66 , C07C211/09 , C07C211/22 , C07C211/27
CPC分类号： C07C209/66
摘要： The present invention relates to an improved method of forming vicinal diamines. The method according to the present invention has the advantage of being highly stereoselective, capable of forming a wide variety of diamines including racemic and enantiomeric forms, and employing readily available starting and reaction materials.In particular the present invention relates to a method of forming vicinal diamines from a bis-imine precursor using nucleophilic additions of organometallic reagents.
摘要翻译：本发明涉及形成连位二胺的改进方法。根据本发明的方法具有高度立体选择性的优点，能够形成各种各样的二胺，包括外消旋和对映体形式，并且使用容易得到的起始和反应物质。特别地，本发明涉及使用亲核添加有机金属试剂从双亚胺前体形成连位二胺的方法。

43. 发明授权

US09295650B2 Functional, cross-linked nanostructures for tandem optical imaging and therapy 有权
标题翻译：用于串联光学成像和治疗的功能性交联纳米结构
公开(公告)号：US09295650B2
公开(公告)日：2016-03-29
申请号：US13697149
申请日：2011-11-17
申请人： William L. Neumann , Richard B. Dorshow , John N. Freskos , Karen L. Wooley , Nam S. Lee , Yun Lin , Guorong Sun
发明人： William L. Neumann , Richard B. Dorshow , John N. Freskos , Karen L. Wooley , Nam S. Lee , Yun Lin , Guorong Sun
IPC分类号： A61K49/00 , A61K9/14 , A61K9/00 , A61K9/107 , A61K9/51 , A61K31/20 , A61K31/70 , A61K38/16 , A61K38/22 , A61K39/395 , A61M5/00
CPC分类号： A61K41/0057 , A61K9/0092 , A61K9/1075 , A61K9/146 , A61K9/5138 , A61K9/5192 , A61K31/20 , A61K31/337 , A61K31/351 , A61K31/70 , A61K31/704 , A61K38/08 , A61K38/16 , A61K38/22 , A61K45/06 , A61K47/6911 , A61K49/0021 , A61K49/0054 , A61K49/0082 , A61K49/0093 , A61M5/007 , A61K2300/00
摘要： The present invention provides optical agents comprising optically functional cross linked supramolecular structures and assemblies useful for tandem optical imaging and therapy. Supramolecular structures and assemblies of the present invention include optically functional shell-cross linked micelles wherein optical functionality is achieved via incorporation of one or more linking groups that include one or more photoactive moieties. The present invention further includes imaging and therapeutic methods using one or more optical agents of the present invention including optically functional shell cross-linked micelles having an associated therapeutic agent.
摘要翻译：本发明提供包含光学功能交联的超分子结构和用于串联光学成像和治疗的组合物的光学剂。本发明的超分子结构和组件包括光学功能的壳交联胶束，其中通过引入一个或多个包含一个或多个光活性部分的连接基团来实现光学官能团。本发明还包括使用本发明的一种或多种光学剂的成像和治疗方法，其包括具有相关治疗剂的光学功能性壳交联胶束。

44. 发明申请

US20140170071A1 Modified Pyrazine Derivatives and Uses Thereof 审中-公开
标题翻译：改性吡嗪衍生物及其用途
公开(公告)号：US20140170071A1
公开(公告)日：2014-06-19
申请号：US14187530
申请日：2014-02-24
申请人： Amruta Poreddy , William L. Neumann
发明人： Amruta Poreddy , William L. Neumann
IPC分类号： A61K49/00
CPC分类号： A61K49/00 , A61K49/0013 , C07D241/26
摘要： In some embodiments, the invention provides modified pyrazine derivatives containing a central pyrazine ring with two secondary amine groups attached directly to the central pyrazine ring and two amino carbonyl groups attached directly to the central pyrazine ring. The secondary amine groups are terminated by alkyl groups containing from 1 to 6 carbons. The amino carbonyl groups can be terminated by a wide range of substituents including, but not limited to, alkyl and alkylene groups, polyether groups, including poly(ethylene glycol) groups, secondary and tertiary amine groups, polyhydroxylated alkyl groups, amino carbonyl groups, amino thioketone groups, and combinations thereof. In some embodiments, the invention provides modified pyrazine derivatives useful as optical agents in a wide variety of biomedical imaging procedures, including diagnostic and imaging procedures. In an embodiment, for example, modified pyrazine derivatives are provided which are useful in monitoring organ and system functioning, for example in monitoring renal system functioning.
摘要翻译：在一些实施方案中，本发明提供了含有中间吡嗪环的改性吡嗪衍生物，其具有直接连接至中央吡嗪环的两个仲胺基团和直接连接至中央吡嗪环的两个氨基羰基基团。仲胺基团被含有1至6个碳原子的烷基封端。氨基羰基可以通过宽范围的取代基来终止，包括但不限于烷基和亚烷基，聚醚基团，包括聚（乙二醇）基团，仲和叔胺基团，多羟基化烷基基团，氨基羰基基团，氨基硫酮基团及其组合。在一些实施方案中，本发明提供了在多种生物医学成像方法中用作光学剂的改性吡嗪衍生物，包括诊断和成像程序。在一个实施方案中，例如，提供了可用于监测器官和系统功能的修饰的吡嗪衍生物，例如在监测肾系统功能。

45. 发明授权

US08722685B2 Pyrazine derivatives and uses thereof in renal monitoring 有权
标题翻译：吡嗪衍生物及其在肾脏监测中的应用
公开(公告)号：US08722685B2
公开(公告)日：2014-05-13
申请号：US13343231
申请日：2012-01-04
申请人： Raghavan Rajagopalan , Richard B. Dorshow , William L. Neumann
发明人： Raghavan Rajagopalan , Richard B. Dorshow , William L. Neumann
IPC分类号： A61K31/4965 , C07D241/02
CPC分类号： A61K31/4965 , A61K31/5377 , A61K49/0021 , A61K49/0052 , A61K49/0054 , C07D241/26
摘要： The present invention relates to pyrazine derivatives such as those represented by Formulas I and II below. X1 to X4 of the compounds of Formulas I and II may be characterized as electron withdrawing groups. In contrast, Y1 to Y4 of the compounds of Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing renal function. In particular, an effective amount of a pyrazine derivative of the invention may be administered into a body of a patient. The pyrazine derivative that is in the body may be exposed to visible and/or infrared light to cause spectral energy to emanate from the pyrazine derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient.
摘要翻译：本发明涉及吡嗪衍生物，例如由下式I和II表示的衍生物。式I和II化合物的X 1至X 4可以表征为吸电子基团。相反，式I和II化合物的Y1至Y4可以表征为给电子基团。本发明的吡嗪衍生物可用于评估肾功能。特别地，有效量的本发明的吡嗪衍生物可以施用于患者体内。身体中的吡嗪衍生物可能暴露于可见光和/或红外光，导致光谱能量从吡嗪衍生物中发出。这种发出的光谱能量可以被检测并用于确定患者的肾功能。

46. 发明授权

US08703100B2 Modified pyrazine derivatives and uses thereof 有权
标题翻译：改性吡嗪衍生物及其用途
公开(公告)号：US08703100B2
公开(公告)日：2014-04-22
申请号：US13140082
申请日：2009-12-17
申请人： Amruta Poreddy , William L. Neumann
发明人： Amruta Poreddy , William L. Neumann
IPC分类号： A61K49/00 , A61P13/12 , A61P13/10 , C07D241/20 , A61K31/4965
CPC分类号： A61K49/00 , A61K49/0013 , C07D241/26
摘要： Provided herein are compounds, preparations and formulations comprising pyrazine derivatives having multiple poly(ethylene glycol) containing substituents. Many of the compounds disclosed herein are excretable by the renal system of a subject or patient and are useful for visualizing the renal system of a subject or patient. Upon excitation by electromagnetic radiation, a number of the compounds disclosed herein exhibit luminescence and are externally detectable when present in the body fluid of a patient or subject. Also provided herein are methods for visualizing the renal system of a subject or patient.
摘要翻译：本文提供了包含具有多个含（乙二醇）取代基的吡嗪衍生物的化合物，制剂和制剂。本文公开的许多化合物可由受试者或患者的肾系统排泄，并且可用于使受试者或患者的肾脏系统可视化。当通过电磁辐射激发时，本文公开的许多化合物表现出发光，并且当存在于患者或受试者的体液中时可外部检测。本文还提供了用于使受试者或患者的肾系统可视化的方法。

47. 发明申请

US20140039191A1 Fluorescent Pyrazine Derivatives and Methods of Using the Same in Assessing Renal Function 有权
标题翻译：荧光吡嗪衍生物及其在肾功能评估中的应用方法
公开(公告)号：US20140039191A1
公开(公告)日：2014-02-06
申请号：US14047733
申请日：2013-10-07
申请人： Raghavan Rajagopalan , Richard B. Dorshow , William L. Neumann , Dennis A. Moore
发明人： Raghavan Rajagopalan , Richard B. Dorshow , William L. Neumann , Dennis A. Moore
IPC分类号： C07D241/28 , C07D241/20
CPC分类号： C07D241/28 , A61K31/4965 , A61K49/0004 , A61K49/0021 , A61K49/0052 , C07D241/20 , C07D241/26
摘要： The present invention relates to pyrazine derivatives such as those represented by Formulas I and II. X1 to X4 of Formulas I and II may be characterized as electron withdrawing groups, while Y1 to Y4 of Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing organ (e.g., kidney) function. In a particular example, an effective amount of a pyrazine derivative that is capable of being renally cleared may be administered into a patient's body. The pyrazine derivative may capable of one or both absorbing and emanating spectral energy of at least about 400 nm (e.g., visible and/or infrared light). At least some of the derivative that is in the body may be exposed to spectral energy and, in turn, spectral energy may emanate from the derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient.
摘要翻译：本发明涉及吡嗪衍生物，例如由式I和II表示的衍生物。式I和II的X 1至X 4可以表征为吸电子基团，而式I和II的Y1至Y4可以表征为给电子基团。本发明的吡嗪衍生物可用于评估器官（例如肾）功能。在具体实例中，有效量的能够被再次清除的吡嗪衍生物可以被施用到患者体内。吡嗪衍生物可以具有一个或两个吸收和发射至少约400nm的光谱能量（例如可见光和/或红外光）。身体中的至少一些衍生物可能暴露于光谱能量，反过来，光谱能量可能来自衍生物。这种发出的光谱能量可以被检测并用于确定患者的肾功能。

48. 发明授权

US08313729B2 Integrated photoactive small molecules and uses thereof 有权
标题翻译：综合光敏小分子及其用途
公开(公告)号：US08313729B2
公开(公告)日：2012-11-20
申请号：US12528630
申请日：2008-02-26
申请人： William L. Neumann , Raghavan Rajagopalan , Dennis A. Moore , Richard B. Dorshow
发明人： William L. Neumann , Raghavan Rajagopalan , Dennis A. Moore , Richard B. Dorshow
IPC分类号： A61B5/00 , A61B8/00 , A61B10/00 , A61K49/00
CPC分类号： A61K49/001 , A61K41/0019 , A61K47/60 , A61K49/0021 , A61K49/0052
摘要： This invention is directed to the general method of transforming non-photoactive bioactive small molecule compounds of known structure and function into photoactive analogs of the small molecules which exhibit both photoactivity and the original biological targeting activity. The general method for the design of the photoactive analogs of the small molecules includes: (a) selecting a desired bioactive molecule; (b) identifying the region of the molecule that contains an aromatic or a heteroaromatic motif; and (c) either replacing said motif with a photoactive functional group of similar size, or modifying said motif to make it photoactive. Other aspects include photoactive analog compounds and photodiagnostic and phototherapeutic uses thereof.
摘要翻译：本发明涉及将具有已知结构和功能的非光活性生物活性小分子化合物转化为具有光活性和原始生物靶向活性的小分子的光活性类似物的一般方法。设计小分子的光活性类似物的一般方法包括：（a）选择所需的生物活性分子; （b）鉴定含有芳族或杂芳族基序的分子的区域; 和（c）用相似尺寸的光活性官能团取代所述基序，或修饰所述基序以使其具有光活性。其他方面包括光敏类似物化合物及其光诊断和光治疗用途。

49. 发明申请

US20120100078A1 Pyrazine Derivatives and Uses Thereof in Renal Monitoring 有权
标题翻译：吡嗪衍生物及其在肾脏监测中的应用
公开(公告)号：US20120100078A1
公开(公告)日：2012-04-26
申请号：US13343231
申请日：2012-01-04
申请人： Raghavan Rajagopalan , Richard B. Dorshow , William L. Neumann
发明人： Raghavan Rajagopalan , Richard B. Dorshow , William L. Neumann
IPC分类号： A61K49/00 , C07D413/04 , C08B37/00 , C07D241/28
CPC分类号： A61K31/4965 , A61K31/5377 , A61K49/0021 , A61K49/0052 , A61K49/0054 , C07D241/26
摘要： The present invention relates to pyrazine derivatives such as those represented by Formulas I and II below. X1 to X4 of the compounds of Formulas I and II may be characterized as electron withdrawing groups. In contrast, Y1 to Y4 of the compounds of Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing renal function. In particular, an effective amount of a pyrazine derivative of the invention may be administered into a body of a patient. The pyrazine derivative that is in the body may be exposed to visible and/or infrared light to cause spectral energy to emanate from the pyrazine derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient.
摘要翻译：本发明涉及吡嗪衍生物，例如由下式I和II表示的衍生物。式I和II化合物的X 1至X 4可以表征为吸电子基团。相反，式I和II化合物的Y1至Y4可以表征为给电子基团。本发明的吡嗪衍生物可用于评估肾功能。特别地，有效量的本发明的吡嗪衍生物可以施用于患者体内。身体中的吡嗪衍生物可能暴露于可见光和/或红外光，导致光谱能量从吡嗪衍生物中发出。这种发出的光谱能量可以被检测并用于确定患者的肾功能。

50. 发明申请

US20120041479A1 Tissue Sealant Compositions, Vascular Closure Devices, and Uses Thereof 有权
标题翻译：组织密封剂组合物，血管闭合装置及其用途
公开(公告)号：US20120041479A1
公开(公告)日：2012-02-16
申请号：US13266161
申请日：2010-04-27
申请人： Bob O. Basore, JR. , William L. Neumann , Richard B. Dorshow , Raghavan Rajagopalan
发明人： Bob O. Basore, JR. , William L. Neumann , Richard B. Dorshow , Raghavan Rajagopalan
IPC分类号： A61B17/03
CPC分类号： A61L24/102 , A61L24/001 , A61L24/0015 , A61L24/0042 , A61L24/046 , A61L24/106 , A61L24/108 , A61L2300/418 , A61L2300/442 , A61L2300/604 , A61L2400/04 , A61L2430/20 , A61L2430/34
摘要： The present invention provides tissue sealant compositions and vasculature closure devices useful for the optical detection of tissue seal and/or clot formation. Compositions and devices of the present invention comprise optical dyes which undergo an observable change as the compositions and/or devices are incorporated into a tissue seal and/or clot, for example a change in fluorescence quantum yield and/or a change in visual color including a change in emission and/or absorption wavelength. Tissue sealants and vasculature closure devices of the present invention are useful for visualizing seal and/or clot formation, for example, during or after surgical procedures, after catheter removal, etc. The present invention further provides methods for formation and optical detection of tissue seals or vasculature puncture closures as well as medical kits useful for the formation and optical detection of tissue seals or vasculature puncture closures.
摘要翻译：本发明提供组织密封剂组合物和脉管系统闭合装置，其可用于光学检测组织密封和/或凝块形成。本发明的组合物和装置包括当组合物和/或装置结合到组织密封和/或凝块中时经历可观察到的变化的光学染料，例如荧光量子产率的变化和/或视觉颜色的变化，包括发射和/或吸收波长的变化。本发明的组织密封剂和血管闭合装置可用于可视化密封和/或血块形成，例如，在外科手术期间或之后，导管移除之后等。本发明还提供用于组织密封的形成和光学检测的方法或脉管系统穿刺闭合件以及可用于组织密封或脉管系统穿刺闭合件的形成和光学检测的医疗套件。

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