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

Naltrexone (1), which is a member of the group of competitive opioid antagonists, shows a strong affinity for μ-receptors and its derivatives have been notable as novel receptor anatgonists. 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 μ-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.