A Quantitative Structure-Activity Study of Anticonvulsant Benzyl N, N-Dimethylcarbamates

概要

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A series of m-and p-substituted benzyl N, N-dimethylcarbamates was prepared then evaluated for anticonvulsant activity in mice by means of the maximal electroshock seizure test. The ED_<50> value correlated well with the hydrophobic (log P, 1-octanol-H_2O partition coefficient), electronic (σ°) and hydrogen bonding (HB) characters of the tested compounds on regression analyses. The relative activity depended parabolically on log P ; the optimum value of hydrophobic character (log P_0) was 1.82. This agrees well with values found empirically for central nervous system depressants (log P_0≃2). Electron-donating substituents enhanced the activity, an indication of interaction between the carbamoyl moiety and an acidic group on the receptor site. Hydrogen bond-accepting ability of the substituent reduced anticonvulsant activity, while non-hydrogen bonders did not. The overall substituent effects were such that the activity of the unsubstituted compound was almost optimum.
社団法人日本薬学会の論文
1982-11-25