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

The synthesis and SAR studies on the N-terminal residue of the ‘address element’ are reported. 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.