Synthesis and Anticonvulsant Activity of 4‐Amino‐N‐(2‐ethylphenyl)benzamide and 4‐Amino‐N‐(2,6‐diethylphenyl)benzamide, Two New Ameltolide Analogues

Abstract

4-Amino-N-(2,6-dimethylphenyl)benzamide or ameltolide is the most potent anticonvulsant benzamide described so far. Two new ameltolide derivatives, i.e. 4-amino-N-(2-ethylphenyl)benzamide and 4-amino-N-(2,6-diethylphenyl)benzamide were synthesized and evaluated in several anticonvulsant models. As measured by their ED50 values, these compounds were superior to phenytoin in the maximal electroshock seizure test. However, these compounds were inactive in the subcutaneous metrazol-, strychnine- or N-methyl-D-aspartate-induced seizure models. Interestingly, while 4-amino-N-(2-ethyl-phenyl)benzamide and 4-amino-N-(2,6-diethylphenyl)benzamide were to some extent less active than ameltolide after intraperitoneal administration, these compounds exhibited a higher efficacy and protective index after oral administration, compared with the parent drug, ameltolide.