Nilsson_1990_J.Med.Chem_33_580

Four beta-lactam analogues (8-11) of oxotremorine were synthesized and assayed for muscarinic and antimuscarinic activity on the isolated guinea pig ileum. The pharmacological results were compared with those obtained previously with the beta-lactam analogue 7 and the 3-, 4-, and 5-methyl-substituted 2-pyrrolidones 2-6. The new compounds were less potent than the corresponding 2-pyrrolidones, regardless of whether they showed agonist (10 and 11), partial agonist (8), or antagonist properties (9) in the ileum assay. The agonists 10 and 11 were about 200-fold less potent than 7. Compounds 8-11 also were less potent than the similarly substituted 2-pyrrolidones in inhibiting the binding of the muscarinic antagonist (-)-[3H]-N-methylscopolamine in homogenates of the rat cerebral cortex.