Morgan T K, Lis R, Lumma W C, Nickisch K, Wohl R A, Phillips G B, Gomez R P, Lampe J W, Di Meo S V, Marisca A J
Medicinal Chemistry Department, Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
J Med Chem. 1990 Apr;33(4):1091-7. doi: 10.1021/jm00166a003.
The synthesis and cardiac electrophysiological activity of 18 N-substituted imidazolylbenzamides or benzene-sulfonamides are described. Compounds 6a,d,f-k and 11 exhibited potency in the in vitro Purkinje fiber assay comparable to that of N-[2-(diethylamino)ethyl]-4- [(methylsulfonyl)amino]benzamide (1, sematilide), a potent selective class III agent which is undergoing clinical trials. These data indicate that the 1H-imidazol-1-yl moiety is a viable replacement for the methylsulfonylamino group for producing class III electrophysiological activity in the N-substituted benzamide series. N-[2-(Diethylamino)ethyl]-4-(1H-imidazol-1-yl)benzamide dihydrochloride (6a) was further studied in two in vivo models of reentrant arrhythmias and showed potency and efficacy comparable to those of 1.
