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1. 发明授权

US4388233A Synthetic substrates for enzyme analysis 失效
标题翻译：用于酶分析的合成底物
公开(公告)号：US4388233A
公开(公告)日：1983-06-14
申请号：US264118
申请日：1981-05-15
申请人： Eugene R. Bissell , Alexander R. Mitchell , Karen W. Pearson , Robert E. Smith
发明人： Eugene R. Bissell , Alexander R. Mitchell , Karen W. Pearson , Robert E. Smith
IPC分类号： C07D311/16 , C07D311/80 , C07K5/068 , C07K5/083 , C07K5/09 , C12Q1/34 , C07C103/52 , C07D311/06
CPC分类号： C07D311/16 , C07D311/80 , C07K5/06086 , C07K5/0806 , C07K5/0815 , C12Q1/34 , C12Q2337/20
摘要： Synthetic substrates are provided which may be represented as A-D. The A moiety thereof includes an amino acid, polypeptide, or derivative thereof. The D moiety thereof includes 7-amino coumarin derivatives having an electron withdrawing substituent group at the 3 position carbon or fused between the 3 and 4 position carbons.
摘要翻译：提供可以表示为A-D的合成基底。其A部分包括氨基酸，多肽或其衍生物。其D部分包括在3位碳上具有吸电子取代基或在3和4位碳之间融合的7-氨基香豆素衍生物。

2. 发明授权

US4409140A Substrates and method for determining enzymes 失效
标题翻译：底物和测定酶的方法
公开(公告)号：US4409140A
公开(公告)日：1983-10-11
申请号：US273518
申请日：1981-06-15
申请人： Robert E. Smith , Eugene R. Bissell
发明人： Robert E. Smith , Eugene R. Bissell
IPC分类号： C07D311/16 , C07K5/06 , C07K5/08 , C07K5/10 , C12Q1/37 , C07C103/52
CPC分类号： C12Q1/37 , C07D311/16 , C07K5/06191 , C07K5/0827 , C07K5/1027 , C12Q2337/24
摘要： A method is disclosed for determining the presence of an enzyme in a biological fluid, which includes the steps of contacting the fluid with a synthetic chromogenic substrate, which is an amino acid derivative of 7-amino-4-trifluoromethylcoumarin; incubating the substrate-containing fluid to effect enzymatic hydrolysis; and fluorometrically determining the presence of the free 7-amino-4-trifluoromethylcoumarin chromophore in the hydrolyzate.
摘要翻译：公开了一种用于确定生物流体中酶的存在的方法，其包括使流体与作为7-氨基-4-三氟甲基香豆素的氨基酸衍生物的合成显色底物接触的步骤; 孵育含底物的液体进行酶水解; 以及荧光测定水解产物中游离的7-氨基-4-三氟甲基香豆素发色团的存在。

3. 发明授权

US5374623A Cysteine protease inhibitors effective for in vivo use 失效
标题翻译：半胱氨酸蛋白酶抑制剂有效用于体内使用
公开(公告)号：US5374623A
公开(公告)日：1994-12-20
申请号：US932791
申请日：1992-08-20
申请人： Mary P. Zimmerman , Eugene R. Bissell , Robert E. Smith
发明人： Mary P. Zimmerman , Eugene R. Bissell , Robert E. Smith
IPC分类号： A61K38/55 , A61P1/02 , A61P29/00 , A61P33/02 , A61P43/00 , C07C237/22 , C07C271/18 , C07C271/22 , C07C279/14 , C07D295/215 , C07K5/065 , A61K37/02 , C07K5/06 , C07K5/08 , C07K5/10
CPC分类号： C07D295/215 , C07C271/18 , C07C271/22 , C07C279/14
摘要： A method of treating medical conditions with proteinase inhibitors of the formula: ##STR1## wherein B is H or an amino acid blocking group for the N-terminal amino acid nitrogen;R.sub.1 is an optionally protected .alpha.-amino acid side chain such that P.sub.2 is the residue of an .alpha.-amino acid selected from the group consisting of phenylalanine (Phe), leucine (Leu), tyrosine (Tyr) and valine (Val), and substituted analogs thereof, particularly including Tyr(OMe);R.sub.2 is an optionally protected .alpha.-amino acid side chain such that P.sub.1 is the residue of an .alpha.-amino acid selected from the group consisting of alanine (Ala), arginine (Arg), aspartic acid (Asp), glutamic acid (Glu), histidine (His), homophenylalanine (HPhe), phenylalanine (Phe), ornithine (Orn), serine (Ser) and threonine (Thr), and substituted analogs thereof;X is a fluorine-free leaving group selected from the group consisting of phenoxy, substituted phenoxy and heterophenoxy;E and G are one or more atoms more electronegative than carbon; andD is hydrogen, methyl or a substituted methyl.
摘要翻译：用下式的蛋白酶抑制剂治疗医学病症的方法：其中B是H或N-末端氨基酸氮的氨基酸封闭基团; R1是任选保护的α-氨基酸侧链，使得P2是选自苯丙氨酸（Phe），亮氨酸（Leu），酪氨酸（Tyr）和缬氨酸（Val）的α-氨基酸的残基，以及其取代的类似物，特别包括Tyr（OMe）; R2是任选保护的α-氨基酸侧链，使得P1是选自丙氨酸（Ala），精氨酸（Arg），天冬氨酸（Asp），谷氨酸（Glu）的α-氨基酸的残基。，组氨酸（His），高苯丙氨酸（HPhe），苯丙氨酸（Phe），鸟氨酸（Orn），丝氨酸（Ser）和苏氨酸（Thr）及其取代的类似物; X是选自苯氧基，取代的苯氧基和异苯氧基的无氟离去基团; E和G是一个或多个比碳更负电的原子; D为氢，甲基或取代甲基。

4. 发明授权

US4294923A Substrates and method for determining enzymes 失效
标题翻译：底物和测定酶的方法
公开(公告)号：US4294923A
公开(公告)日：1981-10-13
申请号：US32444
申请日：1979-04-23
申请人： Robert E. Smith , Eugene R. Bissell
发明人： Robert E. Smith , Eugene R. Bissell
IPC分类号： G01N33/50 , C07D311/00 , C07D311/16 , C07K5/06 , C07K5/08 , C12Q1/37 , C12Q1/38 , C12Q1/36
CPC分类号： C12Q1/37 , C07D311/16 , C07K5/06191 , C07K5/0827 , C12Q2337/24 , Y10S930/28
摘要： A method is disclosed for determining the presence of an enzyme in a biological fluid, which includes the steps of contacting the fluid with a synthetic chromogenic substrate, which is an amino acid derivative of 7-amino-4-trifluoromethylcoumarin; incubating the substrate-containing fluid to effect enzymatic hydrolysis; and fluorometrically determining the presence of the free 7-amino-4-trifluoromethylcoumarin chromophore in the hydrolyzate.
摘要翻译：公开了一种用于确定生物流体中酶的存在的方法，其包括使流体与作为7-氨基-4-三氟甲基香豆素的氨基酸衍生物的合成显色底物接触的步骤; 孵育含底物的液体进行酶水解; 以及荧光测定水解产物中游离的7-氨基-4-三氟甲基香豆素发色团的存在。

5. 发明授权

US06235493B1 Amino acid substituted-cresyl violet, synthetic fluorogenic substrates for the analysis of agents in individual in vivo cells or tissue 失效
标题翻译：氨基酸取代的甲酚紫，用于分析个体体内细胞或组织中的试剂的合成荧光底物
公开(公告)号：US06235493B1
公开(公告)日：2001-05-22
申请号：US09130193
申请日：1998-08-05
申请人： Eugene R. Bissell , Robert F. Smith
发明人： Eugene R. Bissell , Robert F. Smith
IPC分类号： C12Q137
CPC分类号： C12Q1/37 , C12Q2337/00
摘要： The present invention concerns a method to detect the presence of an enzyme in in vivo or in vitro tissue or cell, which method comprises: (a) obtaining a tissue or cell sample to be analyzed; (b) contacting the tissue or cell sample with a substrate of the structure selected from the group consisting of: X=H or one or more natural or synthetic amino acids with or without amino blocking groups, Y=H or one or more natural or synthetic amino acids with or without amino blocking groups, wherein X and Y are the same or different and are amino acid sequences of between about 1 to 1,000,000 amino acids wherein each amino acid is the same or a different amino acid, with the proviso that at least one of X or Y is at least one amino acid; (c) when an enzyme is present in the tissue or cell sample which degrades X, Y and combinations thereof, fluorescent cresyl violet is released in the tissue sample producing a color change; (d) detecting the presence and amount of the enzyme present by the detection and quantification of the fluorescence produced; and (e) optionally comparing the fluorescence to a pre-calibrated fluorescence scale to quantify the fluorescence present. A diagnostic kit for use and a method to prepare amino acid cresyl violet derivatives are described.
摘要翻译：本发明涉及检测体内或体外组织或细胞中酶的存在的方法，该方法包括：（a）获得要分析的组织或细胞样品;（b）使组织或细胞样品与具有或不具有氨基封闭基团的Y = H或一个或多个具有或不具有氨基封闭基团的天然或合成氨基酸的Y = H或一个或多个天然或合成氨基酸的结构的底物，Y = 其中X和Y相同或不同，为约1至1,000,000个氨基酸的氨基酸序列，其中每个氨基酸相同或不同氨基酸，条件是X或Y中的至少一个为至少一个氨基酸;（c）当酶在组织或细胞样品中存在降解X，Y及其组合时，荧光甲酚紫在组织样品中释放产生颜色变化;（d）检测通过检测存在酶并定量产生的荧光; 和（e）可选地将荧光与预校准的荧光标度进行比较以量化存在的荧光。描述了使用的诊断试剂盒和制备氨基酸甲酚紫衍生物的方法。

6. 发明授权

US4505852A 7-Amino-4-trifluoromethylquinolone derived substrates and method for determining enzymes and inhibitors 失效
标题翻译：衍生的7-氨基-4-三氟喹啉酮底物和测定酶和抑制剂的方法
公开(公告)号：US4505852A
公开(公告)日：1985-03-19
申请号：US445280
申请日：1982-11-29
申请人： David W. Rasnick , Eugene R. Bissell
发明人： David W. Rasnick , Eugene R. Bissell
IPC分类号： C07D215/38 , C07K5/06 , C07K5/08 , C07K5/083 , C07K5/087 , C07K5/09 , C07K5/103 , C12Q1/37 , C07C103/52
CPC分类号： C12Q1/37 , C07D215/38 , C07K5/06191 , C07K5/0808 , C07K5/0812 , C07K5/0815 , C07K5/0827 , C07K5/101
摘要： Substrates and their corresponding pharmaceutically acceptable acid salts derived from 7-amino-4-trifluoromethyl-quinolone are disclosed. These substrates are useful for determining the presence of an enzyme or enzyme inhibitor in a biological fluid, wherein the fluid is contacted with a substrate. This mixture is thereafter incubated to effect enzymatic hydrolysis. Subsequently, the presence of the free 7-amino-4-trifluoro-methylquinolone is fluorometrically detected.
摘要翻译：公开了衍生自7-氨基-4-三氟甲基 - 喹诺酮的底物及其相应的药学上可接受的酸式盐。这些底物可用于确定生物流体中酶或酶抑制剂的存在，其中流体与底物接触。然后将该混合物温育以进行酶水解。随后，测定游离的7-氨基-4-三氟 - 甲基喹诺酮的存在。

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