Synthesis of novel twin drug consisting of 8-oxaendoethanotetrahydromorphides with a 1,4-dioxane spacer and its pharmacological activities: μ, κ, and putative ε opioid receptor antagonists

A twin drug consisting of 8-oxaendoethanotetrahydromorphides with a 1,4-dioxane spacer, NS29, was synthesized from a naltrexone derivative. The structure of compound 8, the precursor of NS29, was determined by X-ray crystallography. Monomeric NS28 showed μ opioid receptor antagonist activity, whereas dimeric NS29, consisting of two NS28 units, showed antagonist activities for μ, κ, and the putative ε opioid receptor agonists. Twin drug NS29 and its derivatives are expected to be unique pharmacological tools for investigation of opioid receptor types

Graphical abstractNovel dimeric morphinan derivative with a 1,4-dioxane spacer was synthesized, and showed μ, κ, and putative ε opioid receptor antagonist activities.Figure optionsDownload full-size imageDownload as PowerPoint slide