Synthesis and Biological Evaluation of 14‐Alkoxymorphinans. Part 19

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 [³⁵S]GTPγS functional assays in comparison to the reference compound naltrexone. In the binding assay, compounds 3 – 6 exhibited preference for κ opioid receptors, while the parent compound naltrexone shows preference for μ receptors. In the functional assay, μ antagonist potency of compounds 3 – 6 was in the range of naltrexone, while κ antagonist potency was considerably higher for most novel compounds in comparison to naltrexone.