Stereoisomeric 5,9-dimethyl-2'-hydroxy-2-tetrahydrofurfuryl-6,7-benzomorphans, strong analgesics with non-morphine-like action profiles.
The eight optically active stereoisomers and the corresponding four racemic forms of 5,9-dimethyl-2'-hydroxy-2-tetrahydrofurfuryl-6,7-benzomorphan (1) have been prepared. Depending on their configurations these compounds are potent analgesics or inactive substances in mice. The analgesics attain potencies up to about a hundred times that of morphine but they do not show morphine-like side effects in mice nor do they suppress abstinence in withdrawn morphine dependent monkeys. Their therapeutic ratios are favorable and, in the case of la-1 and la-2, exceptionally good. Configuration-activity relationships are discussed. R configuration of the N-tetrahydrofurfuryl group is a major prerequisite for high analgesic potency.
D000698:Analgesia; D000700:Analgesics / Q000138:chemical synthesis* / Q000633:toxicity; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D006358:Hot Temperature; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D009019:Morphinans / Q000138:chemical synthesis*; D009904:Optical Rotation; D010146:Pain; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans