title: Design, synthesis and biological evaluation of 4-chromanone derivatives as IKr inhibitors.
abstract: Cardiac arrhythmia is a major cause of death in the world. Among many delayed rectifier potassium currents, the rapid delayed rectifier K current (IKr) plays an important role in the repolarization of cardiac tissue. The inhibition of IKr can delay repolarization and lead to an increase in the QT interval of the electrocardiogram, which is the treatment mechanism of Class III antiarrhythmic agents. Therefore, IKr can be considered as the drug target for the treatment of cardiac arrhythmia. In the current study, a series of 4-chromanone compounds (WR1-WR12) were well designed and synthesized as IKr inhibitors. The results disclosed that two compounds displayed potent inhibitory activities against IKr. Moreover, our structure-activity relationship results might provide necessary information for the rational design of inhibitors for IKr.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Lupei
authors.initials: L
authors.lastname: Du
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
mesh_terms: D000200:Action Potentials; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002867:Chromones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000889:Anti-Arrhythmia Agents; D002867:Chromones; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; C068514:4-chromanone