Analgesic narcotic antagonists. 2. 8-Alkymorphinan-6-ones.
A series of 8-alkyl-3-methoxy-17-methylmorphinan-6-ones (3C) and -isomorphinan-6-ones (3T) were prepared by conjugate addition of lithium dialkylcuprates to the corresponding 7,8-didehydro-6-ones 2C and 2T. These 17-methyl compounds were potent analgesics and were converted to mixed narcotic agonists-antagonists 7-10, by replacement of the 17-methyl groups with cycloalkylmethyl moieties. The 8 substituent modified the type of activity observed. One of these compounds, 17-(cyclobutylmethyl)-3-hydroxy-8 beta-methylmorphinan-6-one (10Ca), had an agonist-antagonist ratio of 0.1. Compound 10Ca did not support or cause dependence in rats. This compound, however, appeared to be a typical narcotic agent in morphine-dependent monkeys.
D000085:Acetates / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000882:Haplorhini; D006801:Humans; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D009021:Morphine Dependence / Q000503:physiopathology; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D051381:Rats; D011930:Reaction Time; D013329:Structure-Activity Relationship; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders / Q000209:etiology
D000085:Acetates; D000700:Analgesics; D009019:Morphinans; D009292:Narcotic Antagonists