Design and synthesis of 2-phenylimidazo[1,2-a]pyridines as a novel class of melatonin receptor ligands

A novel class of imidazo[1,2-a]pyridines as melatonin receptor ligands is designed and synthesized. The affinities of 3-(6-methoxy-2-phenylimidazo[1,2-a]pyridine-3-yl)-N-methyl-propionamide 8, N-[2-(6-methoxy-2-phenylimidazo[1,2-a]pyridine-3-yl)-ethyl]-acetamide 13 and N-(1-hydroxy-3-(5-methoxy-2-phenyl-1H-indol-3-yl)propan-2-yl)acetamide 18 are evaluated for binding on melatonin receptors. Compound 8 present good selectivity for MT2 over MT1 (MT1/MT2 = 19) and compound 13 have good affinities for both MT1 (Ki :28 nM) and MT2 (Ki : 8 nM).

Graphical abstractA novel class of imidazo[1,2-a]pyridines as melatonin receptor ligands is designed, and synthesized. The affinities are evaluated for binding on melatonin MT1 and MT2receptors.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis new imidazopyridines variously functionalized. ► Introduction on the imidazopyridine moiety of substituent allowing an interaction with the melatonin receptors. ► One of the elaborated final products turns out to be a good MT2 melatoninergic ligand relatively selective.