3185-51-1Relevant academic research and scientific papers
Design and Synthesis of Naphthalenic Derivatives as Potential Inhibitors of Hydroxyindole-O-methyltransferase
Picard, I. le,Depreux, P.,Lesieur, I.,Delagrange, P.,Bennejean, C.,Renard, P.,Voisin, P.
, p. 183 - 188 (2007/10/03)
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 percent inhibition at a concentration of 10-4 M). Moreover, most of naphthols behaved as enzyme substrates. The ethyl side chain at position 1 was an essential element for optimal biological activity.
