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Common pharmacophores for uncharged human ether-a-go-go-related gene (hERG) blockers

被引：107
作者：
Aronov, Alex M. [1 ]
机构：
[1] Vertex Pharmaceut Inc, Cambridge, MA 02139 USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 23期
关键词：
D O I：
10.1021/jm060500o
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
In silico approaches are widely used to predict human ether-a-go-go-related gene ( hERG) channel blockade. Published pharmacophore models of hERG blockers typically contain a basic nitrogen center flanked by aromatic or hydrophobic groups. However, hERG blockade has been observed in series lacking the basic nitrogen. By utilizing screening data for 194 potent uncharged hERG actives, we propose a pharmacophore for neutral hERG blockers, and provide guidance on eliminating hERG liability in an uncharged hERG active chemical series.
引用
收藏
页码：6917 / 6921
页数：5
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