CHOLINERGIC AGENTS STRUCTURALLY RELATED TO FURTRETHONIUM .1.

A series of 5-substituted-2-(dimethylaminomethyl)-furyl derivatives 4 was prepared, with the aim of discovering novel antimuscarinic agents which are selective for smooth muscle as opposed to cardiac tissue. Bo th non-quaternary and quaternary ammonium compounds were synthesised. The agonist starting point, furtrethonium 3, was gradually transformed into antagonist by introduction of lipophilic and bulky groups in pos ition 5 of this molecule. In particular, the introduction of alpha-hyd roxy-alpha-cyclohexylbenzyl moiety (compound 9b), a lipophilic group c haracteristic of antimuscarinic agents, caused an appreciable increase of the antagonist's potency, and the lengthening of the distance betw een this lipophilic group and the furan ring, obtained by introduction of an ester, ether or amide group, led to some selectivity towards sm ooth muscle (compounds 19, 21, 25). Interestingly, compound 19, with a n ester moiety as a spacer group, proved to be at least 20 times more potent in rat ileum (pK(B) = 7.3) and rat bladder (pK(B) = 7.2) than g uinea-pig atria (pK(B) = 5.9).