Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3.

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Leclerc V, Ettaoussi M, Rami M, Farce A, Boutin JA, Delagrange P, Caignard DH, Renard P, Berthelot P, Yous S

Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3.

Eur J Med Chem. 2011 May;46(5):1622-9. doi: 10.1016/j.ejmech.2011.02.010. Epub 2011 Feb 15.

PubMed ID

21377769 [ View in PubMed

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Abstract

Naphthalenic analogs of MCA-NAT (5-methoxycarbonylamino-N-acetyltryptamine) have been synthesized and evaluated as melatonin receptor ligands. Introduction of a methoxycarbonylamino substituent at the C-7 position of the naphthalenic nucleus yields MT3 selective ligands. This selectivity can be modulated with suitable variations of the C-7 position and the acyl group on the C-1 side chain. We identified new series of compounds with affinity for the MT3 binding site in the nanomolar range, and singled out a selective ligand, (N-[2-(7-methylsulfamoyl-naphth-1-yl)ethyl]acetamide (17), with a Ki of 4.9 nM and selectivity of 1024 and 2040 versus MT1 and MT2 receptors respectively.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Melatonin	Melatonin receptor type 1A	IC 50 (nM)	0.2	N/A	N/A	Details
Melatonin	Melatonin receptor type 1B	IC 50 (nM)	0.53	N/A	N/A	Details