Potential synthetic codeine substitutes: (-)-3-O-aryl-N-methylmorphinans.
A series of novel O-aryl-N-methylmorphinans (7-19) were synthesized by the Ullmann reaction from levorphanol (4) in our search for a synthetic codeine (2) substitute with reduced addition liability. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, (-)-3-phenoxy-N-methylmorphinan (7) is an orally active analgesic comparable in potency to codeine (2), which exhibits decreased physical dependence liability and longer duration of action.
D000818:Animals; D007700:Kinetics; D009019:Morphinans / Q000138:chemical synthesis* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship
D009019:Morphinans; D011957:Receptors, Opioid