Anticonvulsant activity of some 4-aminophenylacetamides

Article abstract of DOI:10.1002/jps.2600760106

A series of 4-aminophenylacetamides was prepared and evaluated for anticonsulvant activity. These compounds were prepared during studies designed to determine the relationship between benzamide-like compounds and anticonsulvant 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 anticonsulvants 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).