Synthesis and evaluation of some stable multisubstrate adducts as inhibitors of catechol O-methyltransferase

Abstract

A new series of methylase inhibitors was designed in which the nucleophilic methyl acceptor is attached to the adenosine and/or homocysteine fragments of the methyl donor, S-adenosylmethionine, to form a multisubstrate adduct. Catecholamine analogs attached through a phenethyl sulfide linkage to 5''-thioadenosine or homocysteine were synthesized with the corresponding methylsulfonium salts. These compounds were assayed as inhibitors of catechol O-methyltransferase, and the adenosylsulfonium salts inhibited the enzyme.