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31. 发明授权

US06191299B1 Method for making aromatic carbonates 失效
标题翻译：制备芳香族碳酸酯的方法
公开(公告)号：US06191299B1
公开(公告)日：2001-02-20
申请号：US09224162
申请日：1998-12-31
申请人： Eric James Pressman , Bruce Fletcher Johnson , Phillip Oscar Moreno , Richard Anthony Battista
发明人： Eric James Pressman , Bruce Fletcher Johnson , Phillip Oscar Moreno , Richard Anthony Battista
IPC分类号： C07C6800
CPC分类号： C07C68/005 , C07C69/96
摘要： An improved method for producing an aromatic carbonate by reacting an aromatic hydroxy compound, carbon monoxide and oxygen in the presence of a catalyst system comprising at least one of palladium or a palladium compound; at least one lead compound; at least one halide source; and at least one desiccant, wherein the ratio of equivalents of lead co-catalyst relative to equivalents of palladium catalyst is optimized to increase reaction rate, as well as to allow production of aromatic carbonate in an economically feasible continuous process.
摘要翻译：一种通过使芳族羟基化合物，一氧化碳和氧在包含钯或钯化合物中的至少一种的催化剂体系的存在下反应制备芳族碳酸酯的改进方法; 至少一种铅化合物; 至少一个卤素源; 和至少一种干燥剂，其中铅助催化剂的当量相对于钯催化剂的当量的比率被优化以提高反应速率，以及允许在经济上可行的连续方法中生产芳族碳酸酯。

32. 发明申请

US20110142759A1 AGENTS AND METHODS FOR THE IMAGING OF MYELIN BASIC PROTEIN 有权
标题翻译：用于成像MYELIN基础蛋白的试剂和方法
公开(公告)号：US20110142759A1
公开(公告)日：2011-06-16
申请号：US13031349
申请日：2011-02-21
申请人： Rong Zhang , Tiberiu Mircea Siclovan , Cristina Abucay Tan Hehir , Victoria Eugenia Cotero , Bruce Fletcher Johnson
发明人： Rong Zhang , Tiberiu Mircea Siclovan , Cristina Abucay Tan Hehir , Victoria Eugenia Cotero , Bruce Fletcher Johnson
IPC分类号： A61K51/04 , C07D213/89 , C07C311/40 , C07D241/04 , A61P43/00 , C12Q1/02
CPC分类号： A61K49/10 , A61K51/04
摘要： The present invention relates to agents capable of binding to myelin basic protein in a subject. Also provided are methods for the detection of myelin-associated neuropathy comprising identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, administering to a subject an agent that binds specifically to myelin basic protein, and determining myelination in the subject by detecting the agent present in the subject. A kit containing the agent or its derivatives for use in detecting myelin basic protein is also provided.
摘要翻译：本发明涉及能够与受试者中的髓磷脂碱性蛋白结合的试剂。还提供了用于检测髓鞘相关神经病变的方法，其包括鉴定处于或伴有髓磷脂相关神经病的风险的受试者，向受试者施用特异性结合髓磷脂碱性蛋白的试剂，以及通过检测来测定受试者的髓鞘形成该主体中存在的代理人。还提供了含有用于检测髓磷脂碱性蛋白质的试剂或其衍生物的试剂盒。

33. 发明申请

US20090142276A1 ALPHA-FLUOROALKYL DIHYDROTETRABENAZINE IMAGING AGENTS AND PROBES 失效
标题翻译： ALPHA-FLOOROALKYL DIHYDROTETRABENAZINE成像剂和探针
公开(公告)号：US20090142276A1
公开(公告)日：2009-06-04
申请号：US12174167
申请日：2008-07-16
申请人： Michael James Rishel , Bruce Fletcher Johnson , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn
发明人： Michael James Rishel , Bruce Fletcher Johnson , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn
IPC分类号： C07D455/06 , A61K49/04
CPC分类号： C07D471/04 , A61K51/0455 , C07B2200/05
摘要： The present invention provides novel alpha-fluoroalkyl dihydrotetrabenazine compounds I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is a C1-C10 aliphatic radical, a C3-C10 cycloaliphatic radical, or a C3-C10 aromatic radical. The alpha-fluoroalkyl dihydrotetrabenazine compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl dihydrotetrabenazine compounds are believed to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl dihydrotetrabenazine compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl dihydrotetrabenazine compounds are useful as probes for the discovery of PET imaging agents.
摘要翻译：本发明提供新的α-氟烷基二氢丁苯那嗪化合物I，其中R1是C1-C10氟化脂族基; R2是氢或C1-C10脂族基; R3是氢或C1-C10脂族基; 并且R 4是C 1 -C 10脂族基团，C 3 -C 10脂环族基团或C 3 -C 10芳族基团。 α-氟烷基二氢丁苯那嗪化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的任一种或两者。认为α-氟烷基二氢丁苯那嗪化合物对VMAT-2具有高亲和力，VMAT-2是涉及人类糖尿病包含氟-18基团的α-氟烷基二氢丁苯那嗪化合物可用作靶向VMAT-2生物标志物的PET显像剂。非放射性α-氟烷基二氢丁苯那嗪化合物可用作发现PET成像剂的探针。

34. 发明申请

US20090110636A1 FLUORINATED DIHYDROTETRABENAZINE ETHER IMAGING AGENTS AND PROBES 有权
标题翻译：氟化二氢异喹啉醚成像剂和探针
公开(公告)号：US20090110636A1
公开(公告)日：2009-04-30
申请号：US11923926
申请日：2007-10-25
申请人： Kande Kankanamalage Dayarathna Amarasinghe , Michael James Rishel , Sean Richard Dinn , Bruce Fletcher Johnson
发明人： Kande Kankanamalage Dayarathna Amarasinghe , Michael James Rishel , Sean Richard Dinn , Bruce Fletcher Johnson
IPC分类号： A61K51/04 , C07D455/06
CPC分类号： C07D455/06 , A61K51/0455
摘要： The present invention provides novel fluorinated ether compounds having structure I wherein R1 is a C2-C10 fluorinated aliphatic radical; R2 is a C1-C10 aliphatic radical, or a C3-C10 cycloaliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is hydrogen or a C1-C10 aliphatic radical. The fluorinated ether compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluorinated ether compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluorinated ether compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabeled fluorinated ether compounds are useful as probes for the discovery of PET imaging agents.
摘要翻译：本发明提供具有结构I的新型氟化醚化合物，其中R 1是C 2 -C 10氟化脂族基; R2是C1-C10脂族基团，或C3-C10脂环族基团; R3是氢或C1-C10脂族基; 并且R 4是氢或C 1 -C 10脂族基。氟化醚化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的任一种或两者。显示氟化醚化合物对于涉及人类糖尿病的生物标志物VMAT-2具有高亲和力。包含氟-18基团的氟化醚化合物可用作靶向VMAT-2生物标志物的PET显像剂。非放射性标记的氟化醚化合物可用作发现PET成像剂的探针。

35. 发明申请

US20130071332A1 LABELED MOLECULAR IMAGING AGENTS AND METHODS OF USE 有权
公开(公告)号：US20130071332A1
公开(公告)日：2013-03-21
申请号：US13234210
申请日：2011-09-16
申请人： Jack Mathew Webster , Bruce Fletcher Johnson , Brian Duh-Lan Lee , Chittari Pabba , Michael James Rishel
发明人： Jack Mathew Webster , Bruce Fletcher Johnson , Brian Duh-Lan Lee , Chittari Pabba , Michael James Rishel
IPC分类号： A61K49/04 , A61P43/00 , A61K49/00 , C07C55/02 , C12Q1/02
CPC分类号： A61K51/0406 , C07B59/001
摘要： Imaging agents are described that comprise labeled substrates capable of being introduced into cells via the cystine/glutamate antiporter. The substrates may be used for imaging or detecting oxidative stress in cells by introducing the labeled agents into cells via the cystine/glutamate antiporter and subsequent detection.

36. 发明授权

US08013161B1 Fluoroalkyl tetrabenazine carbinol compounds as imaging agents and probes 失效
标题翻译：氟烷基四苯并嗪甲醇化合物作为成像剂和探针
公开(公告)号：US08013161B1
公开(公告)日：2011-09-06
申请号：US11952325
申请日：2007-12-07
申请人： Kande Kankanamalage Dayarathna Amarasinghe , Michael James Rishel , Sean Richard Dinn , Bruce Fletcher Johnson
发明人： Kande Kankanamalage Dayarathna Amarasinghe , Michael James Rishel , Sean Richard Dinn , Bruce Fletcher Johnson
IPC分类号： C07D455/06
CPC分类号： C07D455/06 , A61K51/0455 , C07D455/02
摘要： The present invention provides novel fluoroalkyl tetrabenazine carbinol compounds having structure I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; R4 is hydrogen or a C1-C10 aliphatic radical; and R5 is hydrogen, a C1-C10 aliphatic radical, a C2-C10 cycloaliphatic radical, or a C2-C20 aromatic radical. In a particular embodiment, —OR5 is an ester moiety. The fluoroalkyl tetrabenazine carbinol compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluoroalkyl tetrabenazine carbinol compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluoroalkyl tetrabenazine carbinol compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled fluoroalkyl tetrabenazine carbinol compounds are useful as probes for the discovery of PET imaging agents.
摘要翻译：本发明提供具有结构I的新型氟代烷基四苯并嗪甲醇化合物，其中R 1是C 1 -C 10氟化脂族基; R2是C1-C10脂族基团; R3是氢或C1-C10脂族基; R4是氢或C1-C10脂族基; 并且R 5是氢，C 1 -C 10脂族基，C 2 -C 10脂环族基或C 2 -C 20芳族基。在一个具体实施方案中，-OR 5是酯部分。氟烷基四苯并嗪甲醇化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的一种或两种。氟烷基丁苯那嗪甲醇化合物显示对VMAT-2具有高亲和力，VMAT-2是涉及人类糖尿病的生物标记。包含氟-18基团的氟代烷基四苯并嗪甲醇化合物可用作靶向VMAT-2生物标志物的PET显像剂。非放射性氟烷基丁苯那嗪甲醇化合物可用作发现PET成像剂的探针。

37. 发明授权

US07910738B2 Intermediates for alpha-fluoroalkyl tetrabenazine and dihydrotetrabenazine imaging agents and probes 有权
标题翻译： α-氟烷基丁苯那嗪和二氢丁苯那嗪成像剂和探针的中间体
公开(公告)号：US07910738B2
公开(公告)日：2011-03-22
申请号：US11947275
申请日：2007-11-29
申请人： Michael James Rishel , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn , Bruce Fletcher Johnson
发明人： Michael James Rishel , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn , Bruce Fletcher Johnson
IPC分类号： C07D455/06
CPC分类号： C07D455/06 , C07D491/20
摘要： The present invention provides novel fluorophilic compounds having structure VII wherein Q is a carbonyl group, a protected carbonyl group, a hydroxy methine group, or a protected hydroxy methine group; R1 is a C1-C20 aliphatic, C2-C20 cycloaliphatic, or C2-C20 aromatic radical comprising at least one functional group susceptible to reaction with nucleophilic fluoride ion or an electrophilic fluorinating agent; R2 is hydrogen or a C1-C10 aliphatic radical; and R3 is hydrogen or a C1-C10 aliphatic radical. The fluorophilic compounds are provided in both racemic and enantiomerically enriched forms and are useful as intermediates in the preparation of novel PET imaging agents and probes useful in the discovery and performance assessment of PET imaging agents. The fluorophilic compounds are particularly useful in the preparation of PET imaging agents and probes having a high affinity for VMAT-2, a biomarker implicated in human diabetes and other illnesses such as Parkinson's disease.
摘要翻译：本发明提供具有结构VII的新型氟化合物，其中Q为羰基，被保护的羰基，羟基次甲基或被保护的羟基次甲基; R1是包含至少一个与亲核氟离子或亲电氟化剂反应敏感的官能团的C 1 -C 20脂族，C 2 -C 20脂环族或C 2 -C 20芳族基团; R2是氢或C1-C10脂族基; 并且R 3是氢或C 1 -C 10脂族基。亲氟化合物以外消旋和对映体富集的形式提供，并且可用作制备用于PET成像剂的发现和性能评估的新型PET成像剂和探针的中间体。亲氟化合物特别可用于制备对VMAT-2具有高亲和力的PET成像剂和探针，所述VMAT-2是涉及人类糖尿病和其它疾病如帕金森病的生物标志物。

38. 发明授权

US07902364B2 Alpha-fluoroalkyl tetrabenazine and dihydrotetrabenazine imaging agents and probes 有权
标题翻译： α-氟烷基丁苯那嗪和二氢丁苯那嗪成像剂和探针
公开(公告)号：US07902364B2
公开(公告)日：2011-03-08
申请号：US11947215
申请日：2007-11-29
申请人： Michael James Rishel , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn , Bruce Fletcher Johnson
发明人： Michael James Rishel , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn , Bruce Fletcher Johnson
IPC分类号： C07D455/06
CPC分类号： C07D491/12 , A61K51/0455 , C07D471/04
摘要： The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; and R3 is hydrogen or a C1-C10 aliphatic radical. The alpha-fluoroalkyl compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.
摘要翻译：本发明提供具有结构I和相应的二氢丁苯那嗪化合物IV的新的α-氟烷基化合物，其中R 1是C 1 -C 10氟化脂族基; R2是氢或C1-C10脂族基; 并且R 3是氢或C 1 -C 10脂族基。 α-氟烷基化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的任一种或两者。所述α-氟代烷基化合物显示对VMAT-2具有高亲和力，VMAT-2是涉及人类糖尿病的生物标记。包含氟-18基团的α-氟烷基化合物可用作靶向VMAT-2生物标志物的PET成像剂。非放射性α-氟烷基化合物可用作发现PET成像剂的探针。

39. 发明申请

US20090142265A1 ALPHA-FLUOROALKYL TETRABENAZINE AND DIHYDROTETRABENAZINE IMAGING AGENTS AND PROBES 有权
标题翻译：阿尔法 - 氟代苄基四氢萘酮和二氢苯并咪唑成像剂和探针
公开(公告)号：US20090142265A1
公开(公告)日：2009-06-04
申请号：US11947215
申请日：2007-11-29
申请人： Michael James Rishel , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn , Bruce Fletcher Johnson
发明人： Michael James Rishel , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn , Bruce Fletcher Johnson
IPC分类号： A61K51/04 , C07D471/04
CPC分类号： C07D491/12 , A61K51/0455 , C07D471/04
摘要： The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; and R3 is hydrogen or a C1-C10 aliphatic radical. The alpha-fluoroalkyl compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.
摘要翻译：本发明提供具有结构I和相应的二氢丁苯那嗪化合物IV的新的α-氟烷基化合物，其中R 1是C 1 -C 10氟化脂族基; R2是氢或C1-C10脂族基; 并且R 3是氢或C 1 -C 10脂族基。 α-氟烷基化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的任一种或两者。所述α-氟烷基化合物显示对VMAT-2具有高亲和力，VMAT-2是涉及人类糖尿病的生物标记。包含氟-18基团的α-氟烷基化合物可用作靶向VMAT-2生物标志物的PET成像剂。非放射性α-氟烷基化合物可用作发现PET成像剂的探针。

40. 发明授权

US08053578B2 Alpha-fluoroalkyl dihydrotetrabenazine imaging agents and probes 失效
标题翻译： α-氟代烷基二氢丁苯那嗪成像剂和探针
公开(公告)号：US08053578B2
公开(公告)日：2011-11-08
申请号：US12174167
申请日：2008-07-16
申请人： Michael James Rishel , Bruce Fletcher Johnson , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn
发明人： Michael James Rishel , Bruce Fletcher Johnson , Kande Kankanamalage Dayarathna Amarasinghe , Sean Richard Dinn
IPC分类号： C07D455/06
CPC分类号： C07D471/04 , A61K51/0455 , C07B2200/05
摘要： The present invention provides novel alpha-fluoroalkyl dihydrotetrabenazine compounds I wherein R1 is a C1-C10 fluorinated aliphatic radical; R2 is hydrogen or a C1-C10 aliphatic radical; R3 is hydrogen or a C1-C10 aliphatic radical; and R4 is a C1-C10 aliphatic radical, a C3-C10 cycloaliphatic radical, or a C3-C10 aromatic radical. The alpha-fluoroalkyl dihydrotetrabenazine compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The alpha-fluoroalkyl dihydrotetrabenazine compounds are believed to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The alpha-fluoroalkyl dihydrotetrabenazine compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-fluoroalkyl dihydrotetrabenazine compounds are useful as probes for the discovery of PET imaging agents.
摘要翻译：本发明提供新的α-氟烷基二氢丁苯那嗪化合物I，其中R1是C1-C10氟化脂族基; R2是氢或C1-C10脂族基; R3是氢或C1-C10脂族基; 并且R 4是C 1 -C 10脂族基团，C 3 -C 10脂环族基团或C 3 -C 10芳族基团。 α-氟烷基二氢丁苯那嗪化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的任一种或两者。认为α-氟烷基二氢丁苯那嗪化合物对VMAT-2具有高亲和力，VMAT-2是涉及人类糖尿病包含氟-18基团的α-氟烷基二氢丁苯那嗪化合物可用作靶向VMAT-2生物标志物的PET显像剂。非放射性α-氟烷基二氢丁苯那嗪化合物可用作发现PET成像剂的探针。

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