Synthesis of bridged catechol-homocysteine derivatives as potential inhibitors of catechol O-methyltransferase.
Catechol derivatives, covalently joined to homocysteine by sulfide or sulfonium linkages, were synthesized as potential catechol O-methyltransferase multisubstrate inhibitors which might bridge the enzymatic binding sites for the catechol substrate and the amino acid portion of the methyl donor S-adenosylmethionine. These compounds were found to be less effective inhibitors than the product inhibitor S-adenosylhomocysteine.
D000818:Animals; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D006710:Homocysteine; D012436:S-Adenosylmethionine