A new opioid designed multiple ligand derived from the micro opioid agonist endomorphin-2 and the delta opioid antagonist pharmacophore Dmt-Tic

Bioorg Med Chem. 2007 Nov 15;15(22):6876-81. doi: 10.1016/j.bmc.2007.08.047. Epub 2007 Aug 29.

Abstract

Opioid compounds with mixed micro agonist/delta antagonist properties could be used as analgesics with low propensity to induce tolerance and dependence. Here we report the synthesis of a new designed multiple ligand deriving from the micro selective agonist endomorphin-2 and the delta selective antagonist pharmacophore Dmt-Tic. As predicted, the resulting bivalent ligand showed a micro agonist/delta antagonist profile deriving from the corresponding activities of each pharmacophore.

Publication types

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

MeSH terms

  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Dipeptides / pharmacology*
  • Drug Design
  • Ligands
  • Molecular Structure
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, mu / agonists*
  • Structure-Activity Relationship
  • Tetrahydroisoquinolines / chemical synthesis*
  • Tetrahydroisoquinolines / chemistry
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • 2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  • Dipeptides
  • Ligands
  • Oligopeptides
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Tetrahydroisoquinolines
  • endomorphin 2