SYNTHESIS, AFFINITY PROFILE AND FUNCTIONAL ACTIVITY OF MUSCARINIC ANTAGONISTS WITH A 1-METHYL-2-(2,2-ALKYLARYL-1,3-OXATHIOLAN-5-YL)PYRROLIDINE STRUCTURE

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