Pyrrolomorphinans as δ opioid receptor antagonists. The role of steric hindrance in conferring selectivity

F. Farouz-Grant, P. S. Portoghese

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

A series of 2',3'-disubstituted pyrrolomorphinans (5a-i) were synthesized to determine the role of steric hindrance at μ and γ receptors in promoting δ opioid receptor antagonist selectivity. In smooth muscle preparations, five members of the series (5a-c,e,f) possessed K(e) values in the range 2-15 nM and were 6 selective. Since the unsubstituted analogue 4 possessed δ antagonist potency of similar magnitude, but was not δ selective, it is suggested that the 2',3'substitution confers δ selectivity by hindering the interaction of the pharmacophore at μ and γ receptors, while not affecting δ receptors.

Original languageEnglish (US)
Pages (from-to)1977-1981
Number of pages5
JournalJournal of medicinal chemistry
Volume40
Issue number13
DOIs
StatePublished - Jun 20 1997

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