Opioid Binding and in Vitro Profiles of a Series of 4-Hydroxy-3-methoxyindolomorphinans. Transformation of a δ-Selective Ligand into a High Affinity κ-Selective Ligand by Introduction of a 5,14-Substituted Bridge

摘要

In investigation of the effects of 14-substitution in the indolomorphinan series of δ-selective opioid ligands, 5,14-bridged indolomorphinans (4) were prepared from the equivalent dihy-drothebainone acid-catalyzed rearrangement products of the dihydrothevinols. Though the new ligands generally had low affinity for opioid receptors and no δ-selectivity, 4b had high κ-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 κ-opioid receptor binding motif.