Synthesis, affinity profile, and functional activity of muscarinic antagonists with a 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine structure.

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Dei S, Bellucci C, Buccioni M, Ferraroni M, Guandalini L, Manetti D, Martini E, Marucci G, Matucci R, Nesi M, Romanelli MN, Scapecchi S, Teodori E

Synthesis, affinity profile, and functional activity of muscarinic antagonists with a 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine structure.

J Med Chem. 2007 Mar 22;50(6):1409-13. Epub 2007 Feb 17.

PubMed ID

17305327 [ View in PubMed

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Abstract

Starting from a previously studied muscarinic ligand, characterized by a 1,3-oxathiolane nucleus, a new series of muscarinic antagonists were designed by increasing the stereochemical complexity of the molecules. A small library of enantiomeric and diastereomeric 2,2-diphenyl- and 2-cyclohexyl-2-phenyl substituted compounds was thus obtained. All the tested compounds show a high affinity toward cloned human muscarinic hm1-hm5 receptors expressed in CHO cells and a good antagonistic activity on functional assays, with a modest selectivity on rabbit vas deferens.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Methscopolamine bromide	Muscarinic acetylcholine receptor M2	Kd (nM)	0.468	N/A	N/A	Details
Methscopolamine bromide	Muscarinic acetylcholine receptor M3	Kd (nM)	0.617	N/A	N/A	Details