14-Amino, 14-Alkylamino, and 14-Acylamino Analogs of Oxymorphindole. Differential Effects on Opioid Receptor Binding and Functional Profiles

The 14-amino analogue of oxymorphindole (OMI) was synthesized and found to possess δ-opioid binding affinity and selectivity similar to OMI. Substitution of the amino group with alkyl, arylalkyl, and acyl groups had relatively little effect on δ-affinity but δ-selectivity was reduced. In functional assays the 14-phenylacetylamino derivative 6d was a selective δ-agonist whereas the phenethylamino analogue 5d was a μ-agonist and low efficacy δ partial agonist that warrants further investigation as an analgesic with low tolerance and dependence.