Role of benzimidazole (Bid) in the δ-opioid agonist pseudopeptide H-Dmt-Tic-NH-CH2-Bid (UFP-502)

H-Dmt-Tic-NH-CH2-Bid (UFP-502) was the first δ-opioid agonist prepared from the Dmt-Tic pharmacophore. It showed interesting pharmacological properties, such as stimulation of mRNA BDNF expression and antidepression. To evaluate the importance of 1H-benzimidazol-2-yl (Bid) in the induction of δ-agonism, it was substituted by similar heterocycles: The substitution of NH(1) by O or S transforms the reference δ-agonist into δ-antagonists. Phenyl ring of benzimidazole is not important for δ-agonism; in fact 1H-imidazole-2-yl retains δ-agonist activity.

Figure optionsDownload as PowerPoint slide