Design and Synthesis of Naphthalenic Derivatives as Potential Inhibitors of Hydroxyindole-O-methyltransferase

Autor:	P. Voisin, Philippe Delagrange, I. Lesieur, P. Depreux, I. Le Picard, Pierre Renard, Caroline Bennejean
Rok vydání:	1999
Předmět:	Pharmacology chemistry.chemical_classification Ethylene Stereochemistry Hydroxyindole O Methyltransferase Pharmaceutical Science Biological activity chemistry.chemical_compound Enzyme chemistry Amide Side chain Melatonin biosynthesis Moiety
Zdroj:	Pharmacy and Pharmacology Communications. 5:183-188
ISSN:	1460-8081
DOI:	10.1211/146080899128734578
Popis:	Hydroxyindole-O-methyltransferase is an enzyme that catalyses the last step of melatonin biosynthesis. The objective of this work was to design and synthesize potential inhibitors of hydroxyindole-O-methyltransferase. Applying bioisosteric principles to the indolic nucleus, we considered the synthesis of naphthalenic derivatives and varied the nature of substituents at position 7 and the amide group. We also replaced the ethylene moiety at position 1 by its lower and higher homologues, and synthesized C4 retroamides. Of the compounds synthesized, N-[2-(7-naphth-1-yl)]phenylacetamide was the best inhibitor of hydroxyindole-O-methyltransferase (77% inhibition at a concentration of 10−4M). Moreover, most of naphthols behaved as enzyme substrates. The ethyl side chain at position 1 was an essential element for optimal biological activity.
Databáze:	OpenAIRE
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