Catechol O-methyltransferase. 10. 5-Substituted, 3-hydroxy-4-methoxybenzoic acids (isovanillic acids) and 5-substituted, 3-hydroxy-4-methoxybenzaldehydes (isovanillins) as potential inhibitors

Abstract

A series of 5-substituted 3-hydroxy-4-methoxybenzoic acids (isovanillic acids) and -benzaldehydes (isovanillins) were synthesized and evaluated as inhibitors of rat liver catechol O-methyltransferase. The compounds exhibited either noncompetitive or competitive patterns of inhibition when 3,4-dihydroxybenzoic acid was the variable substrate. The benzaldehydes were significantly more potent inhibitors than the corresponding benzoic acids, and electron-withdrawing substituents in the 5 position greatly enhanced their inhibitory activity.