Bioorganic & medicinal chemistry letters

Successful reduction of off-target hERG toxicity by structural modification of a T-type calcium channel blocker

YJ Choi, JH Seo, KJ Shin

Index: Choi, Yeon Jae; Seo, Jae Hong; Shin, Kye Jung Bioorganic and Medicinal Chemistry Letters, 2014 , vol. 24, # 3 p. 880 - 883

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Citation Number: 2

Abstract

Abstract To obtain an optimized T-type calcium channel blocker with reduced off-target hERG toxicity, we modified the structure of the original compound by introducing a zwitterion and reducing the basicity of the nitrogen. Among the structurally modified compounds we designed, compounds 5 and 6, which incorporate amides in place of the original compound's amines, most appreciably alleviated hERG toxicity while maintaining T-type ...