Synthesis and anti-inflammatory activities of novel salicylic acid and diflunisal amide derivatives

Abstract EN

Several compounds were derived from the conversion of the carboxyl group in salicylic acid and diflunisal into amides of various heterocyclic rings such as 2-amino-5-methyl-2- thiazole, 3-amino-5-methylisooxazole, 2-amino-5- methylthio-1,3,4-thiadiazole and 2- aminothiazole.

The synthetic steps involve esterification of the phenolic group in diflunisal, followed by activation of the carboxyl group in aspirin and the esterified difluninal.

Coupling of the corresponding anhydride with the above mentioned heterocyclic rings yielded the intermediates 8-11 and 18-21.

Removal of the acetate generated the designed compounds 12-15 and 22-25.

The anti-inflammatory activities of these compounds were tested using the % inhibition of granuloma.

The results were 64%, 50% and 67% for compounds 25, Roficoxib and Indomethacin respectively.

The ulcerogenic potential of tested compounds indicate that compound 25 in this novel series showed better anti-inflammatory activity and least ulcerogenic side effect relative to Roficoxib and Indomethacin.