1,4-dioxane, a suitable scaffold for the development of novel M(3) muscarinic receptor antagonists.

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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

1,4-dioxane, a suitable scaffold for the development of novel M(3) muscarinic receptor antagonists.

J Med Chem. 2012 Feb 23;55(4):1783-7. doi: 10.1021/jm2013216. Epub 2012 Feb 2.

PubMed ID

22243489 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Methscopolamine bromide	Muscarinic acetylcholine receptor M1	Ki (nM)	0.324	N/A	N/A	Details
Methscopolamine bromide	Muscarinic acetylcholine receptor M2	Ki (nM)	0.178	N/A	N/A	Details
Methscopolamine bromide	Muscarinic acetylcholine receptor M3	Ki (nM)	0.135	N/A	N/A	Details
Oxybutynin	Muscarinic acetylcholine receptor M1	Ki (nM)	2.4	N/A	N/A	Details
Oxybutynin	Muscarinic acetylcholine receptor M2	Ki (nM)	11.75	N/A	N/A	Details
Oxybutynin	Muscarinic acetylcholine receptor M3	Ki (nM)	1.51	N/A	N/A	Details