β-Lactam Analogues of Oxotremorine. 3- and 4-Methyl-Substituted 2-Azetidinones

Article abstract of DOI:10.1021/jm00164a018

Four β-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 β-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 than7.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.