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 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M3 preferring antagonist (±)-17, 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.
1,4-Dioxane, a Suitable Scaffold for the Development of Novel M3 Muscarinic Receptor Antagonists
DEL BELLO, FABIO;GIANNELLA, Mario;PIGINI, Maria;QUAGLIA, Wilma;PIERGENTILI, Alessandro
2012-01-01
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 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M3 preferring antagonist (±)-17, 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.File in questo prodotto:
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