title: Anticholinesterase activity of potential therapeutic 5-(1,3,3-trimethylindolinyl) carbamates.
abstract: 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.
authors.affiliation: U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010.
authors.forename: C N
authors.initials: CN
authors.lastname: Lieske
authors.forename: R T
authors.initials: RT
authors.lastname: Gepp
authors.forename: J H
authors.initials: JH
authors.lastname: Clark
authors.forename: H G
authors.initials: HG
authors.lastname: Meyer
authors.forename: P
authors.initials: P
authors.lastname: Blumbergs
authors.forename: C C
authors.initials: CC
authors.lastname: Tseng
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D004524:Eels; D007202:Indicators and Reagents; D007700:Kinetics; D015394:Molecular Structure; D062025:Organophosphate Poisoning; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007202:Indicators and Reagents; D000110:Acetylcholinesterase