Enantioselectivity of Muscarinic Antagonists. Isomeric 2-Cyclohexyl-2-phenyl-5-(dimethylamino)methyl)-1,3-oxathiolane

The four isomers of 2-cyclohexyl-2-phenyl-[5 (-d imethylamino)methyl]-l,3-oxathiolanmee thiodide were prepared.Their absolute configuration was attributed by means of X-ray crystallography and circular dichroism. The compoundswere tested on rat bladder and guinea pig ileum and heart, and their antimuscarinic potency was evaluated andexpressed as pA2. The results show that the introduction of a chiral center into position 2 brings about a smallbut definite enantioselectivity on rat bladder and guinea pig ileum which is not seen for guinea pig heart. Thissupports the view that differences exist among the muscarinic receptors of these tissues (M2 receptors). Comparisonof the absolute configuration of the antagonists studied in this and in the preceding papel.2 and that of strictly relatedagonists supports the hypothesis of a common binding site for agonists and antagonists of this kind.