Synthesis and Antiarrhythmic Activity of Novel 3-Alkyl-1-[ω-[4-[(alkylsulfonyl)amino]phenyl]-ω-hydroxyalkyl]-1H-imidazolium Salts and Related Compounds

Novel 3-alkyl-1-[ω-[4-[(alkylsulfonyl)amino] phenyl]-ω-hydroxyalkyl]-1H-imidazolium salts were synthesized and investigated for their class III electrophysiological activity on isolated canine cardiac Purkinje fibers and ventricular muscle tissue. Structure-activity relationships are discussed for a series of 25 compounds. Compound 3, 1-[2-hydroxy-2-[4-[(methylsulfonyl) amino] phenyl] ethyl]-3-methyl-1H-imidazolium chloride, prolonged the functional refractory period in anesthetized dogs when given intraduodenally and was also effective in preventing reentrant ventricular tachycardia induced by programmed electrical stimulation when administered intravenously in anesthetized dogs 24 h after an acute myocardial infarction. Both enantiomers of 3 were synthesized. No enantioselectivity was found in the electrophysiological effects of 3.