Synthesis and structure–activity relationships of novel dipeptides and reduced dipeptides as ligands for melanocortin subtype-4 receptor

A series of benzylic piperazines (e.g., 4 and 5) attached to an ‘address element’, the dipeptide H-d-Tic-d-p-Cl-Phe-OH, 3 has been identified as ligands for the melanocortin subtype-4 receptor (MC4R). We describe herein the structure–activity relationship (SAR) studies on the N-terminal residue of the ‘address element’. Several novel dipeptides and reduced dipeptides with high MC4R binding affinities and selectivity emerged from this SAR study.

Graphical abstractThe synthesis and SAR studies on the N-terminal residue of the ‘address element’ are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide