Catechol O-methyltransferase. 8. Structure-activity relationships for inhibtion by 8-hydroxyquinolines

A series of 5- and 7-substituted 8-hydroxyquinolines was evaluated as inhibitors of catechol O-methyltransferase (COMT, E.C. 2.1.1.6). The electronic character of the substituents in the 5 position appeared to have only a small effect if any on the inhibitory activity of these compounds. A significant factor which contributes to the inhibitory activity of these compounds appears to be the nature of the 7-substituent. The structure-activity relationship for this series of inhibitors is discussed relative to the nature of the enzymatic binding site.