Synthesis and biological evaluation of 14-alkoxymorphinans -: Part 19 -: Effect of 14-O-benzylation on the opioid receptor affinity and antagonist potency of naltrexone

The 14-O-benzylnaltrexones 3 - 6 were prepared from naltrexone (2) in several steps. The novel compounds were biologically evaluated in radioligand binding and in [S-35]GTPgammaS functional assays in comparison to the reference compound naltrexone. In the binding assay, compounds 3-6 exhibited preference for K opioid receptors, while the parent compound naltrexone shows preference for mu receptors. In the functional assay, mu antagonist potency of compounds 3-6 was in the range of naltrexone, while K antagonist potency was considerably higher for most novel compounds in comparison to naltrexone.