Design, synthesis and biological evaluation of 4-chromanone derivatives as I_Kr 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 (I_Kr) plays an important role in the repolarization of cardiac tissue. The inhibition of I_Kr 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, I_Kr 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 I_Kr inhibitors. The results disclosed that two compounds displayed potent inhibitory activities against I_Kr. Moreover, our structure-activity relationship results might provide necessary information for the rational design of inhibitors for I_Kr.