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A quantitative assessment of hERG liability as a function of lipophilicity.

Abstract：

:The impact of lipophilicity as a factor contributing to hERG potency is assessed for a large dataset of compounds of differing ionisation type. This dataset is derived from compounds tested in the IonWorks-based in vitro electrophysiology hERG assay at AstraZeneca. Using logistic regression, a quantification of the risk associated with increasing lipophilicity is presented. The anticipated differences between acidic, basic and neutral compounds are apparent in the data but lipophilicity is shown to be a stronger driver for hERG potency than might have been expected. Simple rules defining target lipophilicity values for minimizing hERG liability are derived.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Waring MJ,Johnstone C

doi

10.1016/j.bmcl.2006.12.061

subject

Has Abstract

pub_date

2007-03-15 00:00:00

pages

1759-64

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(06)01475-2

journal_volume

17

pub_type

杂志文章

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