Novel 4-chromanone derivatives, particularly those with bromine and phenylpiperazine substitutions, demonstrate potent in vitro IKr inhibitory activity, providing lead compounds for antiarrhythmic drug development.
Hypothesis-generating for 4-chromanone derivatives in antiarrhythmic development; leaves open in vivo validation and clinical applicability.
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.
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Wang et al. (2014) studied this question.
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