Synthesis of substituted N-[3-(3-methoxyphenyl)propyl] amides as highly potent MT2-selective melatonin ligands

A series of substituted N-[3-(3-methoxyphenyl)propyl] amides were synthesized and their binding affinities towards human melatonin MT1 and MT2 receptors were evaluated. It was discovered that a benzyloxyl substituent incorporated at C6 position of the 3-methoxyphenyl ring dramatically enhanced the MT2 binding affinity and at the same time decreased MT1 binding affinity.

Graphical abstractA benzyloxyl substituent incorporated at C6 position of the 3-methoxyphenyl ring dramatically enhanced the melatonin MT2-binding affinity.Figure optionsDownload full-size imageDownload as PowerPoint slide