TY - JOUR
T1 - 1,4-Dioxane, a suitable scaffold for the development of novel M3 muscarinic receptor antagonists
AU - Del Bello, Fabio
AU - Barocelli, Elisabetta
AU - Bertoni, Simona
AU - Bonifazi, Alessandro
AU - Camalli, Mercedes
AU - Campi, Gaetano
AU - Giannella, Mario
AU - Matucci, Rosanna
AU - Nesi, Marta
AU - Pigini, Maria
AU - Quaglia, Wilma
AU - Piergentili, Alessandro
PY - 2012/2/23
Y1 - 2012/2/23
N2 - 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.
AB - 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.
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U2 - 10.1021/jm2013216
DO - 10.1021/jm2013216
M3 - Article
C2 - 22243489
AN - SCOPUS:84857387188
SN - 0022-2623
VL - 55
SP - 1783
EP - 1787
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 4
ER -