Synthesis of novel twin drug consisting of 8-oxaendoethanotetrahydromorphides with a 1,4-dioxane spacer and its pharmacological activities: is a subset of , mu , and putative epsilon 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 is a subset of opioid receptor antagonist activity, whereas dimeric NS29, consisting of two NS28 units, showed antagonist activities for is a subset of , mu , and the putative epsilon opioid receptor agonists. Twin drug NS29 and its derivatives are expected to be unique pharmacological tools for investigation of opioid receptor types.