title: Analgesic narcotic antagonists. 4. 7-Methyl-N-(cycloalkylmethyl)-3-hydroxymorphinan-6-ones and -isomorphinan-6-ones.
abstract: 3,6-Dimethoxy-7 beta, 17-dimethyl-4-hydroxy-5,6,8,14-tetradehydromorphinan (2) was converted to the 4-deoxy compound 4 and hydrolyzed to a mixture of the B/C-cis (C series) and B/C-trans (T series) isomers of 7,8-didehydromorphinan-6-one, 5. Hydrogenation of the separated isomers gave 7-methyl-6-oxo derivatives 6a. 7,8-Dimethyl-(6b) or 7-methyl-8-ethylmorphinan-6-one (6c) was prepared by reaction of 5 with lithium organocuprates. The analgesic N-methyl compounds 6 were converted to 17-(cyclopropylmethyl) or 17-(cyclobutylmethyl) derivatives 10--13. Some of these compounds had mixed profiles of narcotic agonist-antagonist effects. Studies with drug-dependent monkeys indicated that several of these compounds with an analgesic-antagonist ratio of less than 0.4 substitute for morphine.
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D009019:Morphinans / Q000138:chemical synthesis / Q000494:pharmacology; D009021:Morphine Dependence / Q000503:physiopathology; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control
chemical_list: D000700:Analgesics; D009019:Morphinans; D009292:Narcotic Antagonists