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 M(2)/M(3) muscarinic agonist 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M(3) 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 F; Barocelli E; Bertoni S; Bonifazi A; Camalli M; Campi G; Giannella M; Matucci R; Nesi M; Pigini M; Quaglia W; Piergentili A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 55:(2012), pp. 1783-1787. [10.1021/jm2013216]
1,4-dioxane, a suitable scaffold for the development of novel M₃ muscarinic receptor antagonists.
MATUCCI, ROSANNA;NESI, MARTA;
2012
Abstract
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 M(2)/M(3) muscarinic agonist 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M(3) 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.
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