Syntheses and receptor-binding studies of derivatives of the opioid antagonist naltrexone

Bioorg Med Chem. 2004 Jan 15;12(2):417-21. doi: 10.1016/j.bmc.2003.10.039.

Abstract

Naltrexone (1), which is a member of the group of competitive opioid antagonists, shows a strong affinity for mu-receptors and its derivatives have been notable as novel receptor antagonists. In this paper, the preparation of several naltrexone derivatives is described; these were used to investigate the role of the oxygenated functional groups in facilitating binding to a series of the opioid receptors. The derivatives showed affinity for opioid mu-receptors which was similar to that of naltrexone, but these compounds, which had masked hydroxyl functional groups, displayed a moderate activity. These results suggest that every oxygenated functional group in naltrexone (1) plays an important role in binding to the opioid receptor.

MeSH terms

  • Animals
  • Biochemistry / methods
  • Brain / metabolism
  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical / methods
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / metabolism
  • Guinea Pigs
  • Ligands
  • Mice
  • Naltrexone / analogs & derivatives*
  • Naltrexone / chemistry
  • Narcotic Antagonists* / chemistry*
  • Narcotic Antagonists* / metabolism*
  • Narcotic Antagonists* / pharmacology
  • Receptors, Opioid / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Ligands
  • Narcotic Antagonists
  • Receptors, Opioid
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naltrexone