Influence of the side chain next to C-terminal benzimidazole in opioid pseudopeptides containing the Dmt-Tic pharmacophore

BALBONI, GIANFRANCO;TRAPELLA C;SASAKI Y;AMBO A;MARCZAK E. D;LAZARUS L. H;SALVADORI S.

2009-01-01

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Abstract

To improve the structure-activity studies of the lead delta 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 delta agonism, (2) Phe yielded delta antagonism, (3) and all other residues except Glu (devoid of any activity) gave mu agonism.