Cover Picture: Understanding of Molecular Substructures that Contribute to hERG K+ Channel Blockade: Synthesis and Biological Evaluation of E‐4031 Analogues (ChemMedChem 1/2012)

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Abstract

The cover picture shows the class III anti-arrhythmic agent E-4031, which affects heart rhythm by interacting with the hERG K+ channel resulting in prolongation of the QT interval in the electrocardiogram. In this study, a series of E-4031 derivatives (indicated by arrows) was designed, synthesized and tested for their inhibition of the hERG K+ channel so as to establish structure–activity relationships (SARs). Knowledge gained by this study can be used in the early stages of drug discovery and development to avoid or circumvent hERG K+ channel blockade, thereby reducing the risk of cardiotoxicity, ventricular arrhythmias and sudden death. For more details, see the Full Paper by Adriaan P. IJzerman et al. on p. 107 ff.

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