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

J Med Chem. 2009 Sep 10;52(17):5556-9. doi: 10.1021/jm900686q.

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.

Publication types

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

MeSH terms

  • Animals
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology*
  • Dipeptides / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Narcotic Antagonists* / chemical synthesis
  • Narcotic Antagonists* / chemistry*
  • Narcotic Antagonists* / metabolism
  • Narcotic Antagonists* / pharmacology*
  • Receptors, Opioid / metabolism
  • Substrate Specificity

Substances

  • Benzimidazoles
  • Dipeptides
  • Narcotic Antagonists
  • Receptors, Opioid
  • benzimidazole