潜在治疗性5-（1,3,3-三甲基吲哚啉基）氨基甲酸酯的抗胆碱酯酶活性
Anticholinesterase activity of potential therapeutic 5-(1,3,3-trimethylindolinyl) carbamates.
作者信息
Lieske C N, Gepp R T, Clark J H, Meyer H G, Blumbergs P, Tseng C C
机构信息
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010.
出版信息
J Enzyme Inhib. 1991;5(3):215-23. doi: 10.3109/14756369109080060.
Six N-alkyl and N-aryl 5-(1,3,3-trimethylindolinyl) carbamates were synthesized and studied for their structure-activity relationships in inhibiting eel acetylcholinesterase (AChE). The carbamates were 5-(1,3,3-trimethylindolinyl)N,N-dimethylcarbamate (Cui Xing Ning) (I), 5-(1,3,3-trimethylindolinyl)N,N-diethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl)N-ethylcarbamate (III), 5-(1,3,3-trimethylindolinyl)N,N-diethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl)N-heptylcarbamate (V), and 5-(1,3,3-trimethylindolinyl)N-(3-chlorophenyl)carbamate (VI). The inhibition studies were carried out at 25.0 degrees C at pH 7.60. The rank order of the ki values for eel AChE inhibition is II > V > I > III > VI > IV. Compound II has a greater affinity for the enzyme than any irreversible inhibitor cited in the literature (Kd = 7.14 x 10(-8) M). Our findings should aid in the application of these carbamates (1) for counteracting the cholinergic problems associated with various diseases, and (2) for developing potential pretreatment compounds for organophosphate poisoning.
合成了六种N-烷基和N-芳基5-(1,3,3-三甲基吲哚啉基)氨基甲酸酯，并研究了它们对鳗鱼乙酰胆碱酯酶(AChE)抑制作用的构效关系。这些氨基甲酸酯分别是5-(1,3,3-三甲基吲哚啉基)N,N-二甲基氨基甲酸酯(催醒宁)(I)、5-(1,3,3-三甲基吲哚啉基)N,N-二乙基氨基甲酸酯(IV)、5-(1,3,3-三甲基吲哚啉基)N-乙基氨基甲酸酯(III)、5-(1,3,3-三甲基吲哚啉基)N,N-二乙基氨基甲酸酯(IV)、5-(1,3,3-三甲基吲哚啉基)N-庚基氨基甲酸酯(V)和5-(1,3,3-三甲基吲哚啉基)N-(3-氯苯基)氨基甲酸酯(VI)。抑制研究在25.0℃、pH 7.60条件下进行。对鳗鱼AChE抑制作用的ki值排序为II > V > I > III > VI > IV。化合物II对该酶的亲和力比文献中引用的任何不可逆抑制剂都高(Kd = 7.14×10⁻⁸ M)。我们的研究结果应有助于这些氨基甲酸酯(1)用于对抗与各种疾病相关的胆碱能问题，以及(2)用于开发潜在的有机磷中毒预处理化合物。
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