1,4-Dioxane, a Suitable Scaffold for the Development of Novel M₃ Muscarinic Receptor Antagonists

Abstract

In this study the modulation of the pharmacological profile from agonist to antagonist was successfully obtained by replacing the methyl group in position 6 of the 1,4-dioxane scaffold of the potent M₂/M₃ muscarinic agonist <b>1</b> with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M₃ preferring antagonist (±)-<b>17</b>, which in in vivo study proved to be effective in reducing the volume-induced contractions of rat urinary bladder and was devoid of cardiovascular effects