Melatonergic ligands: Design, synthesis and pharmacological evaluation of novel series of naphthofuranic derivatives

• New naphthofuranic analogues of melatonin were designed and synthesized.
• Prepared compounds showed good binding affinities at both MT1 and MT2 receptors.
• Ligand 6a represents the most interesting compound of this series and behaves as an MT1 partial agonist and MT2 full agonist.
• Lateral chain displacement from position 1–2 has no effect on binding affinity at MT1 and MT2.

Following our research for new melatonergic ligands, herein we report the design, synthesis and biological evaluation of new series of naphthofuranic derivatives as MT1 and MT2 ligands. Binding affinity results of the prepared compounds revealed good binding affinities at both melatonin receptor subtypes. Particularly, compound 6a behaved as an MT1 partial agonist and MT2 full agonist and exhibited an excellent binding affinity at MT2 (Ki = 0.09 nM). In addition, lateral chain displacement from position 1 to 2 of the furan core had no effect on the binding affinity at both MT1 and MT2, while elongation of this side chain, led to decreased melatonergic binding affinities.

Figure optionsDownload as PowerPoint slide