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Cover Picture: Understanding of Molecular Substructures that Contribute to hERG K + Channel Blockade: Synthesis and Biological Evaluation of E‐4031 Analogues (ChemMedChem 1/2012)
Author(s) -
Vilums Maris,
Overman Jeroen,
Klaasse Elisabeth,
Scheel Olaf,
Brussee Johannes,
IJzerman Adriaan P.
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201190057
Subject(s) - herg , cover (algebra) , chemistry , blockade , channel (broadcasting) , stereochemistry , combinatorial chemistry , computational biology , potassium channel , biochemistry , biophysics , computer science , biology , receptor , engineering , computer network , mechanical engineering
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.