Methoctramine-related polymethylene tetraamines. 4. Chirality effect on M2 muscarinic receptor blocking activity.

Chiral methoctramine-related compounds (3 and 4), bearing two asymmetric atoms in the terminal benzylic moieties, were synthesized and evaluated for their blocking activity on M2 and M3 muscarinic receptors of guinea pig left atrium and ileum, respectively. It turned out that insertion of these chiral centers in methoctramine structure is ineffective in the ileum whereas it produces a significant decrease in potency in the atrium when compared to methoctramine (1). Furthermore, the enantiomers of 3 and 4 did not display significant enantioselectivity at both M2 and M3 muscarinic receptors.