Anticonvulsant activity of some 4-aminophenylacetamides

A series of 4-aminophenylacetamides was prepared and evaluated for anticonvulsant activity. These compounds were prepared during studies designed to determine the relationship between benzamide-like compounds and anticonvulsant effects. Unlike benzamides, these phenylacetamides have a methylene group between the aromatic ring and the amide carbonyl. Consequently, formal conjugation is lost, and the number of conformational degrees of freedom has increased. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazol, and in the rotorod assay for neurologic deficit. The more active and selective anticonvulsants prepared in this study were those having an additional aromatic ring as part of the substituent on the amide nitrogen. Compound 16, the 4-aminophenylacetamide derived from 2,6-dimethylaniline, was the most potent compound observed (ED50 = 50.50 mg/kg against electroshock-induced convulsions and ED50 = 93.20 mg/kg against pentylenetetrazol-induced convulsions).