Document Report Card

ID: ALA1126832

Journal: J Med Chem

Title: 2-Amido-8-methoxytetralins: a series of nonindolic melatonin-like agents.

Authors: Copinga S, Tepper PG, Grol CJ, Horn AS, Dubocovich ML.

Abstract: A series of unsubstituted and methoxy-substituted 2-amidotetralins (4a-q) was prepared and evaluated for their ability to compete for 2-[125I]iodomelatonin binding to chicken retinal membranes and for their potency to inhibit the calcium-dependent release of [3H]dopamine from rabbit retina. The lead compound, 2-acetamido-8-methoxytetralin (4j), showed a moderate affinity (Ki = 46 nM) and potency (IC50 = 1.4 nM) at the melatonin receptor. The structural requirements necessary for optimal agonistic activity at the melatonin receptor are as follows. First, the amido group, which should have a small, nonbranched alkyl group, is essential for affinity, and second, the methoxy substituent at the 8-position of the 2-amidotetralin ring is essential for optimal agonistic activity at the melatonin receptor. We concluded that this series of unsubstituted and methoxy-substituted 2-amidotetralins constitutes a class of nonindolic melatonin-like agents that can be used as pharmacological tools to further characterize melatonin receptors and to elucidate the mode of action of melatonin.

CiteXplore: 8411005

DOI: 10.1021/jm00072a008