Influence of the Side Chain Next to C-Terminal Benzimidazole in Opioid Pseudopeptides Containing the Dmt-Tic Pharmacophore

Abstract

To improve the structure−activity studies of the lead δ opioid agonist H-Dmt-Tic-Asp*-Bid, we synthesized and pharmacologically characterized a series of analogues in which the side chain next to 1H-benzimidazole-2-yl (Bid) was substituted by those endowed with different chemical properties. Interesting results were obtained: (1) only Gly, Ala, and Asp resulted in δ agonism, (2) Phe yielded δ antagonism, (3) and all other residues except Glu (devoid of any activity) gave μ agonism