公开(公告)号：US06514987B1

公开(公告)日：2003-02-04

申请号：US09610652

申请日：2000-07-02

申请人： David Cook ,  John E. Merritt ,  Aileen Nerio ,  Henry Rapoport ,  Adonis Stassinopoulos ,  Susan Wollowitz ,  Jan Matejovic ,  William A. Denny

发明人： David Cook ,  John E. Merritt ,  Aileen Nerio ,  Henry Rapoport ,  Adonis Stassinopoulos ,  Susan Wollowitz ,  Jan Matejovic ,  William A. Denny

IPC分类号： A61K3144

CPC分类号： C07D405/12 ,  A61L2/0082 ,  A61M1/0209 ,  B01J20/28 ,  C07D219/10 ,  C07D493/04 ,  C07F9/64

摘要： Compounds and methods for inactivating pathogens in materials are described, including compositions and methods for inactivating pathogens in biological materials such as red blood cell preparations and plasma. The compounds and methods may be used to treat materials intended for in vitro or in vivo use, such as clinical testing or transfusion. The compounds are designed to specifically bind to and react with nucleic acid, and then to degrade to form breakdown products. The degradation reaction is preferably slower than the reaction with nucleic acid.

摘要翻译： 描述了用于灭活材料中的病原体的化合物和方法，包括用于灭活生物材料如红细胞制剂和血浆中的病原体的组合物和方法。 化合物和方法可以用于治疗用于体外或体内使用的物质，例如临床试验或输血。 该化合物被设计成与核酸特异性结合并与其反应，然后降解以形成分解产物。 降解反应优选比与核酸的反应更慢。

公开(公告)号：US6093725A

公开(公告)日：2000-07-25

申请号：US3115

申请日：1998-01-06

申请人： David Cook ,  John E. Merritt ,  Aileen Nerio ,  Henry Rapoport ,  Adonis Stassinopoulos ,  Susan Wollowitz ,  Jan Matejovic

发明人： David Cook ,  John E. Merritt ,  Aileen Nerio ,  Henry Rapoport ,  Adonis Stassinopoulos ,  Susan Wollowitz ,  Jan Matejovic

IPC分类号： A61L2/00 ,  A61M1/02 ,  B01J20/28 ,  C07D219/10 ,  C07D405/12 ,  C07D493/04 ,  C07F9/64 ,  A61K31/44 ,  C07D219/08

CPC分类号： C07D405/12 ,  A61L2/0082 ,  A61L2/0088 ,  A61M1/0209 ,  B01J20/28 ,  C07D219/10 ,  C07D493/04 ,  C07F9/64

摘要： Compounds and methods for inactivating pathogens in materials are described, including compositions and methods for inactivating pathogens in biological materials such as red blood cell preparations and plasma. The compounds and methods may be used to treat materials intended for in vitro or in vivo use, such as clinical testing or transfusion. The compounds are designed to specifically bind to and react with nucleic acid, and then to degrade to form breakdown products. The degradation reaction is preferably slower than the reaction with nucleic acid.

公开(公告)号：US06709810B2

公开(公告)日：2004-03-23

申请号：US09912031

申请日：2001-07-23

申请人： David Cook ,  Adonis Stassinopoulos

发明人： David Cook ,  Adonis Stassinopoulos

IPC分类号： A01N102

CPC分类号： A61L2/0088

摘要： Methods are provided for quenching undesired side reactions of pathogen inactivating compounds in biological materials. In a particular embodiment, methods are provided for quenching undesired side reactions of a pathogen inactivating compound that includes a functional group which is, or which is capable of forming, an electrophilic group. In this embodiment, the material is treated with the pathogen inactivating compound and a quencher, wherein the quencher comprises a nucleophilic functional group that is capable of covalently reacting with the electrophilic group. The electrophilic group on the pathogen inactivating compound is preferably a non-radical cationic group. In one embodiment, the pathogen inactivating compound includes a nucleic acid binding ligand and a mustard group, wherein the mustard group is capable of reacting in situ to form the electrophilic group. Preferred quenchers are thiols, such as glutathione. Biological materials which may be treated include whole blood, red blood cells, blood plasma, and platelets. The methods permit inhibition of the modification of red blood cells in red blood cell containing materials during pathogen inactivation.

摘要翻译： 提供了用于猝灭病原体灭活化合物在生物材料中的不希望的副反应的方法。 在一个具体实施方案中，提供了用于猝灭病原体灭活化合物的不希望的副反应的方法，其包括可亲电子基团或能够形成亲电基团的官能团。 在该实施方案中，用病原体灭活化合物和猝灭剂处理材料，其中猝灭剂包含能够与亲电子基团共价反应的亲核官能团。 病原体灭活化合物上的亲电基团优选为非自由基阳离子基团。 在一个实施方案中，病原体灭活化合物包括核酸结合配体和芥子基团，其中芥末基团能够在原位反应形成亲电子基团。 优选的猝灭剂是硫醇，如谷胱甘肽。 可以治疗的生物材料包括全血，红细胞，血浆和血小板。 该方法允许在病原体灭活期间抑制含红细胞的材料中的红细胞的修饰。

公开(公告)号：US06270952B1

公开(公告)日：2001-08-07

申请号：US09110776

申请日：1998-07-06

申请人： David Cook ,  Adonis Stassinopoulos

发明人： David Cook ,  Adonis Stassinopoulos

IPC分类号： A01N102

CPC分类号： A61L2/0088

摘要： Methods are provided for quenching undesired side reactions of pathogen inactivating compounds in biological materials. In a particular embodiment, methods are provided for quenching undesired side reactions of a pathogen inactivating compound that includes a functional group which is, or which is capable of forming, an electrophilic group. In this embodiment, the material is treated with the pathogen inactivating compound and a quencher, wherein the quencher comprises a nucleophilic functional group that is capable of covalently reacting with the electrophilic group. The electrophilic group on the pathogen inactivating compound is preferably a non-radical cationic group. In one embodiment, the pathogen inactivating compound includes a nucleic acid binding ligand and a mustard group, wherein the mustard group is capable of reacting in situ to form the electrophilic group. Preferred quenchers are thiols, such as glutathione. Biological materials which may be treated include whole blood, red blood cells, blood plasma, and platelets. The methods permit inhibition of the modification of red blood cells in red blood cell containing materials during pathogen inactivation.

摘要翻译： 提供了用于猝灭病原体灭活化合物在生物材料中的不希望的副反应的方法。 在一个具体实施方案中，提供了用于猝灭病原体灭活化合物的不希望的副反应的方法，其包括可亲电子基团或能够形成亲电基团的官能团。 在该实施方案中，用病原体灭活化合物和猝灭剂处理材料，其中猝灭剂包含能够与亲电子基团共价反应的亲核官能团。 病原体灭活化合物上的亲电基团优选为非自由基阳离子基团。 在一个实施方案中，病原体灭活化合物包括核酸结合配体和芥子基团，其中芥末基团能够在原位反应形成亲电子基团。 优选的猝灭剂是硫醇，如谷胱甘肽。 可以治疗的生物材料包括全血，红细胞，血浆和血小板。 该方法允许在病原体灭活期间抑制含红细胞的材料中的红细胞的修饰。

公开(公告)号：US07293985B2

公开(公告)日：2007-11-13

申请号：US10803109

申请日：2004-03-17

申请人： David Cook ,  Adonis Stassinopoulos

发明人： David Cook ,  Adonis Stassinopoulos

IPC分类号： A01N1/02 ,  A01N63/00

CPC分类号： A61L2/0088

摘要： Methods are provided for quenching undesired side reactions of pathogen inactivating compounds in biological materials comprising red blood cells. In a particular embodiment, methods are provided for quenching undesired side reactions of a pathogen inactivating compound that includes a functional group which is, or which is capable of forming, an electrophilic group. In this embodiment, the material is treated with the pathogen inactivating compound and a quencher, wherein the quencher comprises a nucleophilic functional group that is capable of covalently reacting with the electrophilic group. The electrophilic group on the pathogen inactivating compound is preferably a non-radical cationic group. In one embodiment, the pathogen inactivating compound includes a nucleic acid binding ligand and a mustard group, wherein the mustard group is capable of reacting in situ to form the electrophilic group. Preferred quenchers are thiols, such as glutathione. The methods permit inhibition of the modification of red blood cells in red blood cell containing materials during pathogen inactivation.

摘要翻译： 提供了用于猝灭病原体灭活化合物在包含红细胞的生物材料中的不希望的副反应的方法。 在一个具体实施方案中，提供了用于猝灭病原体灭活化合物的不希望的副反应的方法，其包括可亲电子基团或能够形成亲电基团的官能团。 在该实施方案中，用病原体灭活化合物和猝灭剂处理材料，其中猝灭剂包含能够与亲电子基团共价反应的亲核官能团。 病原体灭活化合物上的亲电基团优选为非自由基阳离子基团。 在一个实施方案中，病原体灭活化合物包括核酸结合配体和芥子基团，其中芥末基团能够在原位反应形成亲电子基团。 优选的猝灭剂是硫醇，如谷胱甘肽。 该方法允许在病原体灭活期间抑制含红细胞的材料中的红细胞的修饰。

公开(公告)号：US20060115466A1

公开(公告)日：2006-06-01

申请号：US11264195

申请日：2005-10-31

申请人： Adonis Stassinopoulos

发明人： Adonis Stassinopoulos

IPC分类号： A61K35/14 ,  A01N1/02

CPC分类号： A61L2/0088 ,  A01N1/0205 ,  A01N1/0215 ,  A61K31/198

摘要： Methods are provided for improved quenching of undesired side reactions upon treating a red blood cell composition with a pathogen inactivating compound comprising a nucleic acid binding ligand and a functional group which is, or which is capable of forming, an electrophilic group. In some embodiments, the improved methods use a suitably high concentration of quencher that comprises a nucleophilic functional group that is capable of covalently reacting with the electrophilic group, wherein the treatment occurs within a desired pH range to provide sufficient quenching. Preferred quenchers for use in some of the methods include thiols, such as glutathione, which have been suitably neutralized such that addition to a red blood cell composition results in the desired concentration of quencher at a desirable pH range of 6.8 to 8.5.

摘要翻译： 提供了用于在用包含核酸结合配体和官能团的病原体灭活化合物处理红细胞组合物或改善亲电基团形成功能基团时，改善猝灭不需要的副反应的方法。 在一些实施方案中，改进的方法使用适当高浓度的淬灭剂，其包含能够与亲电子基团共价反应的亲核官能团，其中处理在期望的pH范围内进行以提供足够的淬灭。 用于某些方法的优选猝灭剂包括硫醇，例如谷胱甘肽，其已被适当中和，使得加入红细胞组合物导致所需浓度的猝灭剂在所需pH范围为6.8至8.5。

公开(公告)号：US07655392B2

公开(公告)日：2010-02-02

申请号：US11264195

申请日：2005-10-31

申请人： Adonis Stassinopoulos

发明人： Adonis Stassinopoulos

IPC分类号： A01N1/00

CPC分类号： A61L2/0088 ,  A01N1/0205 ,  A01N1/0215 ,  A61K31/198

摘要： Methods are provided for improved quenching of undesired side reactions upon treating a red blood cell composition with a pathogen inactivating compound comprising a nucleic acid binding ligand and a functional group which is, or which is capable of forming, an electrophilic group. In some embodiments, the improved methods use a suitably high concentration of quencher that comprises a nucleophilic functional group that is capable of covalently reacting with the electrophilic group, wherein the treatment occurs within a desired pH range to provide sufficient quenching. Preferred quenchers for use in some of the methods include thiols, such as glutathione, which have been suitably neutralized such that addition to a red blood cell composition results in the desired concentration of quencher at a desirable pH range of 6.8 to 8.5.

摘要翻译： 提供了用于在用包含核酸结合配体和官能团的病原体灭活化合物处理红细胞组合物或改善亲电基团形成功能基团时，改善猝灭不需要的副反应的方法。 在一些实施方案中，改进的方法使用适当高浓度的淬灭剂，其包含能够与亲电子基团共价反应的亲核官能团，其中处理在期望的pH范围内进行以提供足够的淬灭。 用于某些方法的优选猝灭剂包括硫醇，例如谷胱甘肽，其已被适当中和，使得加入红细胞组合物导致所需浓度的猝灭剂在所需pH范围为6.8至8.5。

公开(公告)号：US06395904B1

公开(公告)日：2002-05-28

申请号：US09486547

申请日：2000-06-06

申请人： John P. Caradonna ,  Subhasish Mukerjee ,  Adonis Stassinopoulos

发明人： John P. Caradonna ,  Subhasish Mukerjee ,  Adonis Stassinopoulos

IPC分类号： C07F1500

CPC分类号： C07F15/025 ,  C07C29/48 ,  C07C235/50 ,  C07C315/02 ,  C07C2602/28 ,  C07D301/02 ,  C07C35/205

摘要： The subject invention provides a binuclear metal complex having structure (I) wherein M1, and M2 are independently selected from the group consisting of Fe, Co, Mn and Ru; wherein m and n are independently +2 or +3; wherein R1, R2, R3, R4, R5 and R6 are independently a linear C1-C6 alkyl, C5-C6 cycloalkyl, phenyl, etc.; wherein (i) R1 and R2, (ii) R3 and R4, or (iii) R5 and R6 independently and optionally are linked covalently and together with the respective adjoining C atom comprise a spirocyclic ring; wherein i, j and k are integers such that 2≦i+j+k≦4; wherein p is 1 or 2, and q is 0, 1 or 2 such that m+n−4=p×q; wherein (i) R1 or R2 and R3 or R4, (ii) R3 or R4 and R4 or R5, or (iii) R1 or R2 and R5 or R6 independently and optionally are linked covalently and together with the respective adjoining C atoms comprise a fused ring; wherein Ar is 1,2-phenylene, 1,2- or 2,3-naphthylene, etc., wherein said Ar is optionally substitued by C1-C6 alkyl or alkoxy; wherein L is N-methylimidazole, N-ethylimidazole, etc.; and wherein X is fluorine, chlorine, bromine, etc. Also provided are methods of oxidation of alkanes, arenes, and sulfides using the binuclear metal complex as a catalyst and a method of preparing said complex.

摘要翻译： 本发明提供具有结构（I）的双核金属络​​合物，其中M1和M2独立地选自Fe，Co，Mn和Ru; 其中m和n独立地是+2或+3; 其中R1，R2，R3，R4，R5和R6独立地为直链C1-C6烷基，C5-C6环烷基，苯基等; 其中（i）R 1和R 2，（ⅱ）R 3和R 4，或（ⅲ）R 5和R 6独立地且任选被共价连接并与相邻的C原子一起包含一个螺环; 其中i，j和k是整数，使得2 <= i + j + k <= 4; 其中p为1或2，q为0,1或2，使得m + n-4 = pxq; 其中（i）R 1或R 2和R 3或R 4，（ⅱ）R 3或R 4和R 4或R 5，或（ⅲ）R 1或R 2和R 5或R 6独立且任选地与相邻的C原子共价连接并连接 稠环; 其中Ar为1,2-亚苯基，1,2-或2,3-亚萘基等，其中所述Ar任选被C 1 -C 6烷基或烷氧基取代; 其中L是N-甲基咪唑，N-乙基咪唑等; 并且其中X是氟，氯，溴等。还提供了使用双核金属络​​合物作为催化剂的烷烃，芳烃和硫化物的氧化方法和制备所述络合物的方法。