1,4-Dioxane, a suitable scaffold for the development of novel M3 muscarinic receptor antagonists

Fabio Del Bello; Elisabetta Barocelli; Simona Bertoni; Alessandro Bonifazi; Mercedes Camalli; Gaetano Campi; Mario Giannella; Rosanna Matucci; Marta Nesi; Maria Pigini; Wilma Quaglia; Alessandro Piergentili

doi:10.1021/jm2013216

1,4-Dioxane, a suitable scaffold for the development of novel M₃ muscarinic receptor antagonists

Fabio Del Bello
, Elisabetta Barocelli
, Simona Bertoni
, Alessandro Bonifazi
, Mercedes Camalli
, Gaetano Campi
, Mario Giannella
, Rosanna Matucci
, Marta Nesi
, Maria Pigini
, Wilma Quaglia
, Alessandro Piergentili

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1783-1787
Number of pages	5
Journal	Journal of medicinal chemistry
Volume	55
Issue number	4
DOIs	https://doi.org/10.1021/jm2013216
State	Published - Feb 23 2012
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm2013216

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title = "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 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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doi = "10.1021/jm2013216",

language = "English (US)",

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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.

UR - https://www.scopus.com/pages/publications/84857387188

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SP - 1783

EP - 1787

JO - Journal of medicinal chemistry

JF - Journal of medicinal chemistry

IS - 4

ER -

1,4-Dioxane, a suitable scaffold for the development of novel M₃ muscarinic receptor antagonists

Abstract

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