Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinediones, novel class III antiarrhythmic agents.
1992
: A series of 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)- pyrimidinedione derivatives were synthesized and studied for their class III electrophysiological activity and class II (beta-blocking) effects in in vitro and in vivo models. Structure-activity relationships are discussed for a series of compounds. Several members of this series prolonged the action potential duration at 75% repolarization of isolated canine Purkinje fibers and were 10-30-fold more potent than d-sotalol. 1,3-Dimethyl-6-[[2-[N-[3-(4-nitrophenyl)propyl]-N- (hydroxyethyl)amino]ethyl]amino]-2,4-(1H,3H)-pyrimidinedione (40), is one of the most potent compounds in this series.
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