Structural determinants of opioid activity in derivatives of 14-aminomorphinones: Effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones

Nick P.R. Nieland, Humphrey A. Moynihan, Simon Carrington, Jillian Broadbear, James H. Woods, John R. Traynor, Stephen M. Husbands, John W. Lewis

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

In recent years there has been substantial interest in the 14-aminodihydromorphinone derivatives methoclocinnamox (MC-CAM) and clocinnamox (C-CAM). To investigate the importance of the cinnamoyl ring substituent, a series of analogues have been prepared with chloro, methyl, and nitro substituents in the 2′ and 4′ positions. Despite some discrepancies between the in vitro and in vivo data, a clear SAR could be observed where the 2′-chloro and 2′-methyl ligands consistently displayed higher efficacy than their 4′-substituted analogues. The new series also followed the well-established SAR that 17-methyl ligands have greater efficacy at the μ opioid receptor than their 17-cyclopropylmethyl counterparts.

Original languageEnglish (US)
Pages (from-to)5333-5338
Number of pages6
JournalJournal of Medicinal Chemistry
Volume49
Issue number17
DOIs
StatePublished - Aug 24 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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