1,4-dioxane, a suitable scaffold for the development of novel M(3) muscarinic receptor antagonists.
Article Details
- CitationCopy to clipboard
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]
- 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