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

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• 作者：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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：February 23, 2012
• 年：2012
• 卷：55
• 期：4
• 页码：1783-1787
• 全文大小：283K
• 年卷期：v.55,no.4(February 23, 2012)
• ISSN：1520-4804

文摘

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 (卤)-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.