Synthesis, biological activity and resistance to proteolytic digestion of new cyclic dermorphin/deltorphin analogues

► Novel cyclic ureidopeptides analogues of dermorphin/deltorphin were synthesized. ► Their in vivo antinociceptive activity and resistance to proteolysis were evaluated. ► N-substituted amides with D-amino acid showed extremely high proteolytic stability. ► Analogue 1 showed significant antinociceptive effect after systemic applications.