Opioid binding and in vitro profiles of a series of 4-hdroxy-3-methoxyindolomorphinans. Transformation of a delta-selective ligand into a high affinity kappa-selective ligand by introduction of a 5,14-substituted bridge

J Med Chem. 2003 Jul 3;46(14):3174-7. doi: 10.1021/jm030801n.

Abstract

In investigation of the effects of 14-substitution in the indolomorphinan series of delta-selective opioid ligands, 5,14-bridged indolomorphinans (4) were prepared from the equivalent dihydrothebainone acid-catalyzed rearrangement products of the dihydrothevinols. Though the new ligands generally had low affinity for opioid receptors and no delta-selectivity, 4b had high kappa-affinity and substantial selectivity which was also seen in the precursor morphinanone (3b). This indicates that the methylbenzylidene-substituted bridge in these compounds is a dominant kappa-opioid receptor binding motif.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology
  • CHO Cells
  • Cricetinae
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Ligands
  • Morphinans / chemical synthesis*
  • Morphinans / chemistry
  • Morphinans / pharmacology
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Opioid, kappa / metabolism*
  • Receptors, Opioid, mu / metabolism

Substances

  • Bridged-Ring Compounds
  • Indoles
  • Ligands
  • Morphinans
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu