Synthesis of nitroindole derivatives with high affinity and selectivity for melatoninergic binding sites MT(3).

Article Details

Citation

Leclerc V, Yous S, Delagrange P, Boutin JA, Renard P, Lesieur D

Synthesis of nitroindole derivatives with high affinity and selectivity for melatoninergic binding sites MT(3).

J Med Chem. 2002 Apr 25;45(9):1853-9.

PubMed ID
11960497 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MelatoninMelatonin receptor type 1AKi (nM)0.12N/AN/ADetails
MelatoninMelatonin receptor type 1BKi (nM)0.31N/AN/ADetails