Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines.
A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001921:Brain / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008722:Methods; D051379:Mice; D008968:Molecular Conformation; D009020:Morphine / Q000037:antagonists & inhibitors; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000700:Analgesics; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D009020:Morphine