Synthesis and antiarrhythmic activity of novel 3-alkyl-1-[omega-[4-[(alkylsulfonyl)amino]phenyl]-omega- hydroxyalkyl]-1H-imidazolium salts and related compounds. 2.
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.
Lis
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R
Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
Davey
D D
DD
Morgan
T K
TK
Lumma
W C
WC
Wohl
R A
RA
Jain
V K
VK
Wan
C N
CN
Argentieri
T M
TM
Sullivan
M E
ME
Cantor
E H
EH
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
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D013449:Sulfonamides