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

J Med Chem. 2006 Aug 24;49(17):5333-8. doi: 10.1021/jm0604777.


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 mu opioid receptor than their 17-cyclopropylmethyl counterparts.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cinnamates / chemical synthesis
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Codeine / analogs & derivatives*
  • Codeine / chemical synthesis
  • Codeine / pharmacology*
  • Drug Design
  • Ligands
  • Molecular Structure
  • Morphine Derivatives / chemical synthesis
  • Morphine Derivatives / chemistry
  • Morphine Derivatives / pharmacology*
  • Receptors, Opioid, mu / drug effects*
  • Stereoisomerism
  • Structure-Activity Relationship


  • Cinnamates
  • Ligands
  • Morphine Derivatives
  • Receptors, Opioid, mu
  • clocinnamox
  • Codeine