3-(2-BENZOFURANYL)QUINUCLIDIN-2-ENE DERIVATIVES - NOVEL MUSCARINIC ANTAGONISTS

A series of 26 derivatives of the novel muscarinic antagonist 3-(2-ben zofuranyl) quinuclidin-2-ene (1) has been synthesized and evaluated fo r muscarinic and antimuscarinic properties. The affinity of the compou nds was determined by competition experiments in homogenates of cerebr al cortex, heart, parotid gland, and urinary bladder from guinea pigs using (-)-[H-3]-3-quinuclidinyl benzilate as the radioligand, and the antimuscarinic potency was determined in a functional assay on isolate d guinea pig urinary bladder using carbachol as the agonist. The 5-flu orobenzofuranyl derivative was slightly more potent than 1. The 7-brom o-substituted 8 displayed a 14-fold tissue selectivity ratio for musca rinic receptors in the cortex versus the parotid gland. Comparative mo lecular field analysis and quantitative structure-activity relationshi p models were developed for this series of substituted benzofuranyl de rivatives.