SYNTHESIS AND PLATELET AGGREGATION INHIBITORY ACTIVITY OF ANALOGUES OF 4-2-(1H-IMIDAZOL-1-YL)-1- (4- SUBSTITUTEDPHENYL) ETHOXY METHYL BENZOIC ACIDS

Analogues of 4- 2-( 1H-imidazol-1-yl )-1-(4-substituted-phenyl) ethoxy methyl benzoic acids were synthesized for searching of more potent and selective thromboxane synthetase inhibitors. All title compounds are first reported.Results of preliminary pharmacological tests showed that all title compounds have activity against thromboxane synthetase, i.e. inhibiting platelet aggregation induced by AA in vitro with rabbit. Compound 15 is the most potent. Its activity is 55.6% of that of Dazoxiben in comparison of IC₅₀. The change of group substituted on benzene would af fect inhibitory activity to thrcmboxane synthtase. Esters are more potent than the parent acids. This is probably due to the greater platelet permeability of the more lipophilic ester prior to intraplatelet deesterification.NBS was applied to the preparation of p- bromonethylbenzoic ester. This method increased the yield and simplified operating process.