Acylmorphinans. A novel class of potent analgesic agents.
A series of novel 2- and 3-acylmorphinans (8-14) was synthesized in our search for a potent analgesic agent with low addiction potential. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, the levorotatory 3-acetyl-N-(cyclopropylmethyl)morphinan (12) was found to be an orally active analgesic, comparable in potency to morphine (1), yet only weakly able to substitute for morphine (1) in morphine-dependent rats.
Mohacsi
E
E
O'Brien
J
J
Blount
J
J
Sepinwall
J
J
D000698:Analgesia; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003061:Codeine; D006801:Humans; D007981:Levorphanol; D009682:Magnetic Resonance Spectroscopy; D009019:Morphinans / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D009020:Morphine; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D019966:Substance-Related Disorders
D009019:Morphinans; D011957:Receptors, Opioid; D007981:Levorphanol; D009020:Morphine; C046476:3-acetyl-N-(cyclpropylmethyl)morphinan; D003061:Codeine