A quantitative structure-activity study of anticonvulsant benzyl N,N-dimethylcarbamates.

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Abstract
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 ED50 value correlated well with the hydrophobic (log P, 1-octanol-H2O partition coefficient), electronic (.sigma..degree.) and H 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 P0) was 1.82. This agrees well with values found empirically for CNS depressants (log P0 .simeq. 2). Electron-donating substituents enhanced the activity, an indication of interaction between the carbamoyl moiety and an acidic group on the receptor site. H bond-accepting ability of the substituent reduced anticonvulsant activity, while non-H bonders did not. The overall substituent effects were such that the activity of the unsubstituted compound was almost optimum.