5-allyl-9-oxobenzomorphans. 3. Potent narcotic antagonists and analgesics-antagonists in the series of substituted 2',9beta-dihydroxy-6,7-benzomorphans.
5-Allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan methiodide (1) has been converted in a selective two-step process to the corresponding 9beta-hydroxy intermediates 4 and 6, which in turn were transformed via modified von Braun demethylation-acylation to the amides 11 and 21, respectively. These were reduced and demethylated to give a series of 5-allyl-2',9beta-dihydroxy-2-substituted 6,7-benzomorphans 13 and 23, some of which have been found to be highly potent narcotic antagonists and/or analgesics. The resolution of the most interesting compounds (23a and 23b) and pharmacological properties of the optical isomers are also described. Reduction of the double bond in 13 and 23 to give 14 and 24, with one exception, did not appreciably alter pharmacological profiles, while cyclization to the tetrahydrofuranobenzomorphans 25 substantially reduced the level of activities.
D000701:Analgesics, Opioid / Q000138:chemical synthesis*; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis*; D009020:Morphine / Q000037:antagonists & inhibitors; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D010111:Oxymorphone / Q000037:antagonists & inhibitors; D011809:Quinones / Q000037:antagonists & inhibitors; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013035:Spasm / Q000517:prevention & control; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D001575:Benzomorphans; D009019:Morphinans; D009292:Narcotic Antagonists; D011809:Quinones; D009020:Morphine; D010111:Oxymorphone