Anticholinesterase Activity of Potential Therapeutic 5-(1,3,3-Trimethylindolinyl)Carbamates

摘要

Six N-alkyl and N-aryl 5-(1,3,3-trimethylindolinyl) carbamates were synthesizedand 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-methylcarbamate (II), 5-(1,3,3-trimethylindolinyl)N-ethylcarbamate (III), 5-(1,3,3-trimethylindolinyl)N,Ndiethylcarbamate (IV), 5-(1,3,3-trimethylindolinyl)N-heptylcarbamate (V), and 5-(1,3,3-trimethylindolinyl) N-(3-cholorophenyl)carbamate (VI). The inhibition studies were carried out at 25.0 deg C at pH 7.60. The rank order of the ki values for eel AChE inhibition is 11 > V > I > Ill > Vi > IV. Compound 11 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. Acetylcholinesterase, carbamates, inhibition