Author(s): Leclerc V, Yous S, Delagrange P, Boutin JA, Renard P,
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Abstract The aim of this study was to synthesize selective ligands for melatoninergic subtype receptors that could elucidate the physiological role of melatonin (N-acetyl-5-methoxytryptamine, 1). So, we first investigated the role of a nitro substituent in the 4-, 6-, or 7-position of the indole heterocycle. Comparatively to melatonin, its analogues that nitrated in the 6- or 7-position (6 and 22) lose MT(3) but retain good MT(1) and MT(2) affinities, whereas the 4-nitro isomer (5) shows very high affinity (nanomolar) and selectivity for the MT(3) binding sites. N-Methylation of the indole nucleus of compound 5 potentiates these effects and affords the most potent and selective MT(3) ligand (17). The 2-iodo derivatives (12 and 10) of compounds 5 and 17 have also been synthesized to evaluate their binding profile with a view to further develop MT(3) selective radioligands.
This article was published in J Med Chem
and referenced in Research & Reviews: Journal of Chemistry