Synthesis and characterization of thiazolo- and thiazinomorphinans and their intermediate products as novel opioid-active derivatives

摘要

A new procedure was elaborated for the synthesis of potentially opioid-active thiazolo- and thiazinomorphinans. These derivatives and some intermediates related with the synthesis were tested in opioid receptor binding studies. Two compounds showed remarkable μ opioid activities and specificities. The ligand-stimulated [ 35S]GTPγS assays confirmed for both compounds the potent full agonist profile at the μ receptor and for the benzothiazinomorphinan derivative also the μ receptor full agonist character. The structures of these remarkably effective compounds were analyzed with the aid of computational chemistry calculations.