Novel C-Terminus Modifications of the Dmt-Tic Motif:  A New Class of Dipeptide Analogues Showing Altered Pharmacological Profiles Toward the Opioid Receptors

The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic dipeptide analogues are described. These resulting analogues bearing different C-terminal functionalities were found to bind to the human δ receptor with high affinity. One specific class of dipeptides bearing urea/thiourea functionalities showed partial to full activation of the δ receptor. Several dipeptides also showed good binding affinities with full activation of the human κ receptor, a novel property for those ligands.