Synthesis and pharmacology of metabolically stable tert-butyl ethers of morphine and levorphanol.
3-O-tert-Butylmorphine (5) was prepared from 6-O-acetylmorphine (3) via alkylation with N,N-dimethylformamide di-tert-butyl acetal, followed by hydrolytic removal of the 3-(dimethylamino)-2-propenoate group. The same process was used to prepare the tert-butyl ether of levorphanol (6), (-)-3-tert-butoxy-N-methylmorphinan (8). Both 5 and 8 exhibited in vitro affinity for the opiate receptor comparable to codeine and had analgesic properties in the writhing test. Only 5 exhibited activity in the tail-flick procedure and neither compound showed significant antitussive activity.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001667:Binding, Competitive; D007981:Levorphanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D009271:Naltrexone / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects
D000700:Analgesics; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D007981:Levorphanol; C036160:3-O-tert-butylmorphine; C036161:3-O-tert-butyllevorphanol; D009271:Naltrexone