Structure–activity relationship of the novel bivalent and C-terminal modified analogues of endomorphin-2

Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) is a putative endogenous μ-opioid receptor ligand. To develop potent analgesics with less side effects related to it, we used the methods of dimerization and C-terminal modification. Through dimerization we got the ‘balanced agonists’ with potent analgesic activity and we have developed the structure–activity relationship between the selectivity and the distance of the two tyrosine pharmacophores. Modification at the C-terminal increased the selectivity of endomorphin-2 to μ-opioid receptor with binding affinity conserved.