Catechol O-methyltransferase. 10. 5-Substituted 3-hydroxy-4-methoxybenzoic acids (isovanillic acids) and...

A series of 5-substituted 3-hydroxy-4-methoxybenzoic acids (isovanillic acids) and -benzaldehydes (isovanillins) have been 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.