Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands

Bioorg Med Chem Lett. 2017 Feb 1;27(3):666-669. doi: 10.1016/j.bmcl.2016.11.057. Epub 2016 Nov 22.

Abstract

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.

Keywords: Analgesic tolerance; Benzylideneoxymorphone; Delta opioid receptor; Mu opioid receptor; Oxymorphone.

Publication types

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

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry*
  • Analgesics / therapeutic use
  • Animals
  • Benzylidene Compounds / chemistry
  • Ligands*
  • Mice
  • Oxymorphone / analogs & derivatives*
  • Oxymorphone / chemical synthesis
  • Oxymorphone / chemistry*
  • Oxymorphone / therapeutic use
  • Pain / drug therapy
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / metabolism*

Substances

  • 7-benzylideneoxymorphone
  • Analgesics
  • Benzylidene Compounds
  • Ligands
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Oxymorphone