Synthesis and biological activity of analogues of beta-chlornaltrexamine and beta-funaltrexamine at opioid receptors.
beta-Chlornaltrexamine and beta-funaltrexamine analogues 4-7 with different length "arms" to which an electrophilic moiety is attached were synthesized in an effort to obtain affinity labels that would selectively and irreversibly block specific opioid receptor types and subtypes. One of the compounds, 4, was a potent, irreversible blocker of opioid receptors in the guinea pig ileum and mouse vas deferens preparations. The results of this study suggest that nucleophiles that are remote from the recognition locus are capable of alkylation by reactive electrophiles.
D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D013329:Structure-Activity Relationship
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009271:Naltrexone; C017120:chlornaltrexamine; C024524:beta-funaltrexamine