Esters of Substituted Benzoic Acids as Anti-thrombotic Agents

Aliphatic esters of protocatechuic acid (PA, 1), vanillic acid (VA, 9) and gallic acid (GA, 18) were prepared and their anti-thrombotic effects were evaluated in the mouse model of thrombosis. The aliphatic groups included methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, n-amyl and cyclohexyl. n-Amyl ester of PA (7), i-propyl and cyclohexyl esters of VA (13 and 17 respectively) and ethyl ester of GA (20) treatment significantly lowered the death rate and increased the recovery from paralysis due to the thrombotic challenge. From the limited analogs available, it was tentatively concluded that the structural conformation, where carboxy oxygen (=O or -O) of the carboxyl group (COOH) at $C_1$ and the oxygen function at $C_3(either\; OH\; or\; OCH_3)$ are closely situated, is favorable for the esters of PA, VA and GA to be more antithrombotic.