title: Interactions of narcotics an their antagonists with human serum esterase. IX: structure-activity relationships of morphinans and morphines.
abstract: The interaction of 21 morphinan and 25 morphine derivatives with human serum esterase was examined. The behavior of these drugs closely parallels that of their simpler analogues, benzomorphans, studied previously: all have affinity for an allosteric modifying site at which agonists accelerate enzyme action and, except for 6-ketodihydromorphines, all are also competitive inhibitors of the enzyme. The results suggest that both ring C of morphinans and morphines and the furan ring of morphines contribute to binding to the allosteric site; so does increase in the size of the N-alkyl group, but alkylation at C-6 or C-7 is unfavorable for such binding. A hydroxyl group at C-6 or C-14, or a methoxyl group at C-3 are also unfavorable. As with benzomorphans, we found that the natural (--)-morphine configuration is more sensitive than its optical antipode to structural influences on its affinity for the allosteric site.
mesh_terms: D055598:Chemical Phenomena; D002621:Chemistry; D004950:Esterases / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008968:Molecular Conformation; D009019:Morphinans / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D009019:Morphinans; D009022:Morphine Derivatives; D004950:Esterases