Synthesis and biological evaluation of 14-alkoxymorphinans, V: 6-Deoxyocyprodime, an opioid antagonist with decreased mu receptor selectivity in comparison to cyprodime.
N-Cyclopropylmethyl-4,14-dimethoxymorphinan (4) and N-cyclopropylmethyl-4-hydroxy-14-methoxymorphinan (5) have been prepared from cyprodime (1) by Wolff-Kishner reduction. Pharmacological studies (mouse vas deferens and guinea pig ileum preparations) revealed that there was no significant decrease of 4 in antagonist activity but in mu selectivity when compared with 1. The phenol 5 showed partial agonism at mu, kappa and delta receptors.
Schmidhammer
H
H
Institute of Organic and Pharmaceutical Chemistry, University of Innsbruck, Austria.
Jennewein
H K
HK
Smith
C F
CF
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu; D014649:Vas Deferens / Q000187:drug effects
D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C058450:cyprodime; C070125:6-deoxocyprodime; C070127:N-cyclopropylmethyl-4-hydroxy-14-methoxymorphinan