Role of benzimidazole (Bid) in the delta-opioid agonist pseudopeptide H-Dmt-Tic-NH-CH(2)-Bid (UFP-502)

Bioorg Med Chem. 2008 Mar 15;16(6):3032-8. doi: 10.1016/j.bmc.2007.12.032. Epub 2007 Dec 23.


H-Dmt-Tic-NH-CH(2)-Bid (UFP-502) was the first delta-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 delta-agonism, it was substituted by similar heterocycles: The substitution of NH(1) by O or S transforms the reference delta-agonist into delta-antagonists. Phenyl ring of benzimidazole is not important for delta-agonism; in fact 1H-imidazole-2-yl retains delta-agonist activity.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles*
  • Brain-Derived Neurotrophic Factor / genetics
  • Humans
  • Molecular Mimicry*
  • Opioid Peptides / chemistry*
  • RNA, Messenger / drug effects
  • Receptors, Opioid, delta / agonists*
  • Structure-Activity Relationship
  • Up-Regulation / drug effects
  • Up-Regulation / genetics


  • Benzimidazoles
  • Brain-Derived Neurotrophic Factor
  • Opioid Peptides
  • RNA, Messenger
  • Receptors, Opioid, delta
  • benzimidazole