Synthesis, Affinity Profile, and Functional Activity of Muscarinic Antagonists with a 1-Methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine Structure

• DOI: 10.1021/jm061374r
• Publication Date: 2007-02-17T11:53:42Z
• Authors: Silvia Dei; Cristina Bellucci; Michela Buccioni; Marta Ferraroni; Luca Guandalini; Dina Manetti; Elisabetta Martini; Gabriella Marucci; Rosanna Matucci; Marta Nesi; Maria Novella Rom...; Serena Scapecchi; Elisabetta Teodori
• Keywords: Pyrrolidine; Structure–activity relationship

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