Synthesis of nitroindole derivatives with high affinity and selectivity for melatoninergic binding sites MT(3).
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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
Drug Target Property Measurement pH Temperature (°C) Melatonin Melatonin receptor type 1A Ki (nM) 0.12 N/A N/A Details Melatonin Melatonin receptor type 1B Ki (nM) 0.31 N/A N/A Details