Synthesis and evaluation of some stable multisubstrate adducts as inhibitors of catechol O-methyltransferase.
A new series of methylase inhibitors has been 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". In the present case, catecholamine analogues attached through a phenethyl sulfide linkage to 5'-thioadenosine or homocysteine have been synthesized, together with the corresponding methylsulfonium salts. These compounds were assayed as inhibitors of catechol O-methyltransferase, and the adenosylsulfonium salts (4) were found to be inhibitors of the enzyme.
D065098:Catechol O-Methyltransferase Inhibitors; D055598:Chemical Phenomena; D002621:Chemistry; D009861:Onium Compounds / Q000138:chemical synthesis*; D013452:Sulfonium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D065098:Catechol O-Methyltransferase Inhibitors; D009861:Onium Compounds; D013452:Sulfonium Compounds