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

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 MT 3 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 MT 3 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 MT 1 and MT 2 receptors respectively.