3-Deoxyclocinnamox: The first high-affinity, nonpeptide μ-opioid antagonist lacking a phenolic hydroxyl group

I. Derrick, C. L. Neilan, J. Andes, S. M. Husbands, J. H. Woods, J. R. Traynor, J. W. Lewis

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The C3-substituent in morphinan opioids is of critical importance; the 3-OH group is usually associated with very much higher affinity for μ-receptors than H or -OMe. However in this series of 14β-cinnamoylamino derivatives the codeinones (e.g. methoclocinnamox, MC-CAM) had unexpectedly high μ-opioid receptor affinity, similar to that of the morphinone (clocinnamox, C-CAM). The current report relates to the synthesis and in vitro evaluation of deoxyclocinnamox (DOC-CAM) which acted as a high-affinity opioid antagonist similar to C-CAM but with greater μ selectivity. Thus it appears that the C3-substituent does not play a major role in the binding of the 14β-cinnamoyl series and that the cinnamoyl group itself may in fact be the dominant binding feature.

Original languageEnglish
Pages (from-to)3348-3350
Number of pages3
JournalJournal of Medicinal Chemistry
Volume43
Issue number17
DOIs
Publication statusPublished - 1 Aug 2000

ASJC Scopus subject areas

  • Organic Chemistry

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