title: Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinediones, novel class III antiarrhythmic agents.
abstract: 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.
authors.affiliation: Medicinal Chemistry Department, Mitsui Toatsu Chemicals Inc., Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Katakami
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: M
authors.initials: M
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: N
authors.initials: N
authors.lastname: Kawauchi
authors.forename: T
authors.initials: T
authors.lastname: Nobori
authors.forename: K
authors.initials: K
authors.lastname: San-nohe
authors.forename: T
authors.initials: T
authors.lastname: Kaiho
authors.forename: J
authors.initials: J
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones