title: Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
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.
authors: Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
authors: R
authors: R
authors: Lis
authors: D D
authors: DD
authors: Davey
authors: T K
authors: TK
authors: Morgan
authors: W C
authors: WC
authors: Lumma
authors: R A
authors: RA
authors: Wohl
authors: V K
authors: VK
authors: Jain
authors: C N
authors: CN
authors: Wan
authors: T M
authors: TM
authors: Argentieri
authors: M E
authors: ME
authors: Sullivan
authors: E H
authors: EH
authors: Cantor
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D013610:Tachycardia / Q000517:prevention & control
chemical_list: D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D013449:Sulfonamides