Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2

  • J Med Chem. 1987 Dec;30(12):2303-9. doi: 10.1021/jm00395a021.
R Lis  1 ,  D D Davey ,  T K Morgan Jr ,  W C Lumma Jr ,  R A Wohl ,  V K Jain ,  C N Wan ,  T M Argentieri ,  M E Sullivan ,  E H Cantor
Affiliations
  • 1. Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
PMID: 3681900 DOI: 10.1021/jm00395a021
Abstract

Novel analogues of the class III antiarrhythmic agent 1-[2-hydroxy-2-[4-[(methylsulfonyl)amino]phenyl]ethyl]-3-methyl-1H- imidazolium chloride, 1 (CK-1649), were prepared 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 11 compounds. One compound, N-[4-[1-hydroxy-2-(4,5-dihydro-2-methyl-1H-imidazol-1- yl)ethyl]phenyl]methanesulfonamide hydrochloride, 9, was comparable in activity to 1 in vitro and prolonged the functional refractory period in anesthetized dogs when given intraduodenally. Unlike 1, compound 9 was ineffective at preventing ventricular tachycardia induced by programmed electrical stimulation in anesthetized dogs 24 h after an acute myocardial infarction.

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