title: Analgesics and narcotic antagonists in the benzomorphan and 8-oxamorphinan series. 5.
abstract: 3-Methoxy-8-oxamorphinans 9 have been prepared from the corresponding 5-allyl-9alpha-hydroxy-2'-methoxy-2-methyl-6,7-benzomorphans 7. The former compounds were transformed to the 3-hydroxy-8-oxamorphinans 6, a class of potent analgesics and analgesic-antagonists. In ring C of the morphinan nucleus substitution of 8-CH2 with oxygen enhanced both analgesic and antagonist activities, while replacement of hydrogen with a methyl group at C-14 in these compounds enhanced antagonist activity and decreased analgesic activity. Tetrahydrofuranobenzomorphans 3 and 3-hydroxy-8-oxaisomorphinans 4 displayed lower levels of activity. Structural requirements for antagonist activity are discussed.
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans; D009292:Narcotic Antagonists