1190882-46-2Relevant academic research and scientific papers
Structural determinants for histamine H1 affinity, hERG affinity and QTc prolongation in a series of terfenadine analogs
Aslanian, Robert,Piwinski, John J.,Zhu, Xiaohong,Priestley, Tony,Sorota, Steve,Du, Xiao-Yi,Zhang, Xue-Song,McLeod, Robbie L.,West, Robert E.,Williams, Shirley M.,Hey, John A.
supporting information; experimental part, p. 5043 - 5047 (2010/03/31)
In the late 1980's reports linking the non-sedating antihistamines terfenadine and astemizole with torsades de pointes, a form of ventricular tachyarrhythmia that can degenerate into ventricular fibrillation and sudden death, appeared in the clinical literature. A substantial body of evidence demonstrates that the arrhythmogenic effect of these cardiotoxic antihistamines, as well as a number of structurally related compounds, results from prolongation of the QT interval due to suppression of specific delayed rectifier ventricular K+ currents via blockade of the hERG-IKr channel. In order to better understand the structural requirements for hERG and H1 binding for terfenadine, a series of analogs of terfenadine has been prepared and studied in both in vitro and in vivo hERG and H1 assays.
