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31. 发明授权

US5243073A Hexadentate ligands useful in radiographic imaging agents 失效
标题翻译：用于放射成像剂的十六进制配体
公开(公告)号：US5243073A
公开(公告)日：1993-09-07
申请号：US627176
申请日：1990-12-14
申请人： William L. Neumann , Raghavan Rajagopalan
发明人： William L. Neumann , Raghavan Rajagopalan
IPC分类号： A61K51/00 , A61K51/04 , C07B59/00 , C07C225/14 , C07C229/04 , C07C229/16 , C07C237/06 , C07C271/20 , C07C275/14 , C07F9/50 , C07F9/70 , C07F13/00
CPC分类号： C07F13/005 , A61K51/0478 , C07B59/004 , C07C229/16 , C07F9/5027 , A61K2123/00
摘要： The present invention relates to novel preorganized hexadentate ligands suitable for complexing with a radionuclide to form imaging agents for diagnostic purposes. The ligands have the formula: ##STR1## wherein a) R.sub.2 is hydrogen and R.sub.3 is methyl; or R.sub.2 and R.sub.3 together form a methoxy benzene ring.
摘要翻译：本发明涉及适于与放射性核素络合以形成用于诊断目的的成像剂的新型预组织六齿配体。配体具有下式：其中a）R 2是氢，R 3是甲基; 或R 2和R 3一起形成甲氧基苯环。

32. 发明申请

US20080318917A1 POLYETHYLENE GLYCOLATED SUPEROXIDE DISMUTASE MIMETICS 有权
标题翻译：聚乙烯甘油超氧化物歧化酶
公开(公告)号：US20080318917A1
公开(公告)日：2008-12-25
申请号：US11766221
申请日：2007-06-21
申请人： Daniela Salvemini , William L. Neumann , Samuel Tremont , Kishore Udipi , Amruta Reddy Poreddy
发明人： Daniela Salvemini , William L. Neumann , Samuel Tremont , Kishore Udipi , Amruta Reddy Poreddy
IPC分类号： A61K31/555 , A61P25/00 , A61P37/00 , C07D259/00
CPC分类号： A61K47/60
摘要： Compounds and methods for utilizing compounds comprising a superoxide dismutase mimetic covalently linked to polyethylene glycol. Methods are also provided for preparing a superoxide dismutase mimetic covalently linked to a polyethylene glycol, the methods comprising reacting an activated polyethylene glycol with a superoxide, dismutase mimetic, or alternatively, reacting a superoxide dismutase mimetic with an activated polyethylene glycol. A method is also provided for preventing or treating a disease or disorder in which superoxide anions are implicated, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound comprising a superoxide dismutase mimetic covalently linked to a polyethylene glycol. Methods of determining the safety and efficacy of the compounds ere also provided. Methods for determining the safety and efficacy can include methods in lab animals and humans.
摘要翻译：用于利用包含与聚乙二醇共价连接的超氧化物歧化酶模拟物的化合物的化合物和方法。还提供了用于制备与聚乙二醇共价连接的超氧化物歧化酶模拟物的方法，所述方法包括使活化的聚乙二醇与超氧化物反应，模拟物歧化酶，或者将超氧化物歧化酶模拟物与活化的聚乙二醇反应。还提供了一种用于预防或治疗涉及超氧化物阴离子的疾病或病症的方法，包括向有需要的受试者施用治疗有效量的包含与聚乙二醇共价连接的超氧化物歧化酶模拟物的化合物。还提供了确定化合物的安全性和功效的方法。确定安全性和功效的方法可以包括实验动物和人类的方法。

33. 发明授权

US07015223B1 Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade 失效
标题翻译：用于选择性抑制凝血级联的取代的多环芳基和杂芳基1,2,4-三嗪酮
公开(公告)号：US07015223B1
公开(公告)日：2006-03-21
申请号：US10275856
申请日：2000-11-20
申请人： Michael S. South , Ashton T. Hamme, II , William L. Neumann , Darin E. Jones , Melvin L. Rueppel
发明人： Michael S. South , Ashton T. Hamme, II , William L. Neumann , Darin E. Jones , Melvin L. Rueppel
IPC分类号： C07D253/07 , C07D413/02 , A61K31/53 , A61P7/02
CPC分类号： C07D401/04
摘要： The invention relates to substituted polycyclic aryl and heteroaryl pyrimidinone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.
摘要翻译：本发明涉及可用作凝血级联丝氨酸蛋白酶抑制剂的取代的多环芳基和杂芳基嘧啶酮化合物，以及用于治疗和预防各种血栓形成疾病（包括冠状动脉和脑血管疾病）的抗凝血治疗的化合物，组合物和方法。

34. 发明授权

US06969715B2 6-membered heterocyclic compounds useful for selective inhibition of the coagulation cascade 失效
标题翻译：可用于选择性抑制凝血级联的6元杂环化合物
公开(公告)号：US06969715B2
公开(公告)日：2005-11-29
申请号：US10263637
申请日：2002-10-03
申请人： Michael S. South , Ronald K. Webber , Horng-Chih Huang , Mihaly V. Toth , Alan E. Moormann , Jeffery S. Snyder , Jeffrey A. Scholten , Danny J. Garland , Melvin L. Rueppel , William L. Neumann , Scott Long , Wei Huang , John Trujillo , John J. Parlow , Darin E. Jones , Brenda Case , Michael J. Hayes
发明人： Michael S. South , Ronald K. Webber , Horng-Chih Huang , Mihaly V. Toth , Alan E. Moormann , Jeffery S. Snyder , Jeffrey A. Scholten , Danny J. Garland , Melvin L. Rueppel , William L. Neumann , Scott Long , Wei Huang , John Trujillo , John J. Parlow , Darin E. Jones , Brenda Case , Michael J. Hayes
IPC分类号： C07D249/12 , A61K31/451 , A61K31/495 , A61K31/50 , A61K31/513 , A61K31/53 , A61K31/535 , A61K45/00 , A61P7/02 , A61P9/10 , A61P43/00 , C07C257/18 , C07D207/32 , C07D211/56 , C07D211/98 , C07D213/74 , C07D231/38 , C07D231/48 , C07D237/04 , C07D239/10 , C07D239/22 , C07D241/04 , C07D241/20 , C07D249/14 , C07D253/06 , C07D253/075 , C07D263/48 , C07D265/02 , C07D277/42 , C07D307/22 , C07D333/36 , C07D401/12 , C07D403/10 , C07D413/12 , C07D471/04
CPC分类号： C07D213/74 , C07C257/18 , C07C2601/04 , C07C2601/10 , C07D207/32 , C07D211/56 , C07D211/98 , C07D231/38 , C07D231/48 , C07D237/04 , C07D239/10 , C07D239/22 , C07D241/04 , C07D241/20 , C07D249/14 , C07D253/06 , C07D253/075 , C07D263/48 , C07D265/02 , C07D277/42 , C07D307/22 , C07D333/36 , C07D401/12 , C07D403/10 , C07D413/12 , C07D471/04
摘要： The present invention relates to compounds, and prodrugs thereof, compositions and methods useful for preventing and treating thrombotic conditions in mammals. The compounds of the present invention, and prodrugs thereof, selectively inhibit certain proteases of the coagulation cascade.
摘要翻译：本发明涉及化合物及其前药，可用于预防和治疗哺乳动物血栓形成病症的组合物和方法。本发明的化合物及其前药选择性地抑制凝血级联的某些蛋白酶。

35. 发明授权

US06664255B1 Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade 失效
标题翻译：用于选择性抑制凝血级联的取代的多环芳基和杂芳基吡嗪酮
公开(公告)号：US06664255B1
公开(公告)日：2003-12-16
申请号：US09574752
申请日：2000-05-18
申请人： Michael South , John J. Parlow , Darin E. Jones , Brenda Case , Tom Dice , Richard Lindmark , Michael J. Hayes , Melvin L. Rueppel , Horng-Chih Huang , Wei Huang , Scott A. Long , Matthew Mahoney , William L. Neumann , David Reitz , John I. Trujillo , Ching-Cheng Wang , Rhonda Wood , Qingping Zeng , Rick Fenton , Gary W. Franklin , Carrie Kusturin
发明人： Michael South , John J. Parlow , Darin E. Jones , Brenda Case , Tom Dice , Richard Lindmark , Michael J. Hayes , Melvin L. Rueppel , Horng-Chih Huang , Wei Huang , Scott A. Long , Matthew Mahoney , William L. Neumann , David Reitz , John I. Trujillo , Ching-Cheng Wang , Rhonda Wood , Qingping Zeng , Rick Fenton , Gary W. Franklin , Carrie Kusturin
IPC分类号： C07D24120
CPC分类号： C07D417/12 , A61K38/00 , C07D241/20 , C07D401/12 , C07D403/12 , C07D405/04 , C07D409/04 , C07D409/12 , C07D413/12 , C07K5/06139 , C07K5/06191
摘要： The invention relates to substituted polycyclic aryl and heteroaryl pyrazinone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.
摘要翻译：本发明涉及可用作凝血级联丝氨酸蛋白酶抑制剂的取代的多环芳基和杂芳基吡嗪酮化合物，以及用于治疗和预防各种血栓形成病症（包括冠状动脉和脑血管疾病）的抗凝血治疗的化合物，组合物和方法。

36. 发明授权

US06525041B1 Manganese or iron complexes of nitrogen-containing macrocyclic ligands effective as catalysts for dismutating superoxide 失效
标题翻译：含氮大环配体的锰或铁络合物有效作为用于分解超氧化物的催化剂
公开(公告)号：US06525041B1
公开(公告)日：2003-02-25
申请号：US08596887
申请日：1996-03-14
申请人： William L. Neumann , Dennis P. Riley , Randy H. Weiss , Susan L. Henke , Patrick J. Lennon , Karl W. Aston
发明人： William L. Neumann , Dennis P. Riley , Randy H. Weiss , Susan L. Henke , Patrick J. Lennon , Karl W. Aston
IPC分类号： A61K31555
CPC分类号： C07D259/00 , C07F9/6524 , C07F13/005 , C07F15/025 , Y10S977/904 , Y10S977/915
摘要： Low molecular weight mimics of superoxide dismutase (SOD) represented by the formula: wherein R, R′, R1, R′1, R2, R′2, R3, R′3, R4, R′4, R5, R′5, R6, R′6, R7, R′7, R8, R′8, R9, and R′9, M, X, Y, Z and n are as defined herein, useful as therapeutic agents for inflammatory disease states and disorders, ischemic/reperfusion injury, stroke, atherosclerosis, and all other conditions of oxidant-induced tissue damage or injury.
摘要翻译：由下式表示的超氧化物歧化酶（SOD）的低分子量模拟物：其中R，R'，R1，R'1，R2，R'2，R3，R'3，R4，R'4，R5，R'5 ，R6，R'6，R7，R'7，R8，R'8，R9和R'9，M，X，Y，Z和n如本文所定义，可用作炎性疾病状态和病症的治疗剂，缺血/再灌注损伤，中风，动脉粥样硬化和所有其他氧化剂诱导的组织损伤或损伤的病症。

37. 发明授权

US06214817B1 Substituted pyridino pentaazamacrocyle complexes having superoxide dismutase activity 有权
标题翻译：具有超氧化物歧化酶活性的取代的吡啶并五氮杂胞苷复合物
公开(公告)号：US06214817B1
公开(公告)日：2001-04-10
申请号：US09398120
申请日：1999-09-16
申请人： Dennis P. Riley , William L. Neumann , Susan L. Henke , Patrick Lennon , Karl W. Aston , Daniela Salvemini , James A. Sikorski , Yvette M. Fobian , Margaret Lanahan Grapperhaus , Carrie L. Kusturin
发明人： Dennis P. Riley , William L. Neumann , Susan L. Henke , Patrick Lennon , Karl W. Aston , Daniela Salvemini , James A. Sikorski , Yvette M. Fobian , Margaret Lanahan Grapperhaus , Carrie L. Kusturin
IPC分类号： C07D48722
CPC分类号： C07D471/06 , A61K31/555 , C07D471/08 , C07F13/005 , Y02A50/473
摘要： The present invention relates to compounds which are effective as catalysts for dismutating superoxide and, more particularly, the manganese or iron complexes of substituted, unsaturated heterocyclic pentaazacyclopentadecane ligands which catalytically dismutate superoxide.
摘要翻译：本发明涉及有效作为用于分解超氧化物的催化剂的化合物，更具体地说，涉及催化分解超氧化物的取代的，不饱和杂环五氮杂环十五烷配体的锰或铁络合物。

38. 发明授权

US5976498A Methods of diagnostic image analysis using metal complexes of nitrogen-containing macrocyclic ligands 失效
标题翻译：使用含氮大环配体的金属络合物进行诊断图像分析的方法
公开(公告)号：US5976498A
公开(公告)日：1999-11-02
申请号：US698612
申请日：1996-08-16
申请人： William L. Neumann , Dennis P. Riley , Randy H. Weiss , Susan L. Henke , Patrick J. Lennon , Karl W. Aston
发明人： William L. Neumann , Dennis P. Riley , Randy H. Weiss , Susan L. Henke , Patrick J. Lennon , Karl W. Aston
IPC分类号： C07D259/00 , A61K49/00 , A61K49/04 , A61K49/06 , A61K51/00 , A61K51/04 , C07F3/00 , G01N31/00
CPC分类号： A61K49/06 , A61K51/0482
摘要： The present invention is directed to complexes represented by the formula: ##STR1## wherein R, R', R.sub.1, R'.sub.1, R.sub.2, R'.sub.2, R.sub.3, R'.sub.3, R.sub.4, R'.sub.4, R.sub.5, R'.sub.5, R.sub.6, R'.sub.6, R.sub.7, R'.sub.7, R.sub.8, R'.sub.8, R.sub.9, R'.sub.9, M, X, Y, Z and n are defined herein for use as contrast agents in diagnostic imaging.
摘要翻译：本发明涉及由下式表示的络合物：其中R，R'，R 1，R'1，R 2，R'2，R 3，R'3，R 4，R'4，R 5，R'5， R'6，R7，R'7，R8，R'8，R9，R'9，M，X，Y，Z和n在本文中定义为用作诊断成像中的造影剂。

39. 发明申请

US20140186267A1 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：US20140186267A1
公开(公告)日：2014-07-03
申请号：US14196188
申请日：2014-03-04
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： 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。

40. 发明授权

US08697033B2 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：US08697033B2
公开(公告)日：2014-04-15
申请号：US13140107
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： 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。

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