Lead Optimization Using Matched Molecular Pairs: Inclusion of Contextual Information for Enhanced Prediction of hERG Inhibition, Solubility, and Lipophilicity

被引：94

作者：

Papadatos, George ^{[1
]}

Alkarouri, Muhammad ^{[1
]}

Gillet, Valerie J. ^{[1
]}

Willett, Peter ^{[1
]}

Kadirkamanathan, Visakan ^{[2
]}

Luscombe, Christopher N. ^{[3
]}

Bravi, Gianpaolo ^{[3
]}

Richmond, Nicola J. ^{[3
]}

Pickett, Stephen D. ^{[3
]}

Hussain, Jameed ^{[3
]}

Pritchard, John M. ^{[3
]}

Cooper, Anthony W. J. ^{[3
]}

Macdonald, Simon J. F. ^{[3
]}

机构：

[1] Univ Sheffield, Informat Sch, Sheffield S1 4DP, S Yorkshire, England

[2] Univ Sheffield, Dept Automat Control & Syst Engn, Sheffield S1 3JD, S Yorkshire, England

[3] GlaxoSmithKline Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2010年 / 50卷 / 10期

基金：

英国工程与自然科学研究理事会;

关键词：

CHEMICAL REPLACEMENTS; SIMILARITY; SUBSTITUENTS; CHEMISTRY; BINDING; QSAR;

D O I：

10.1021/ci100258p

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Previous studies of the analysis of molecular matched pairs (MMPs) have often assumed that the effect of a substructural transformation on a molecular property is independent of the context (i.e., the local structural environment in which that transformation occurs). Experiments with large sets of hERG, solubility, and lipophilicity data demonstrate that the inclusion of contextual information can enhance the predictive power of MMP analyses, with significant trends (both positive and negative) being identified that are not apparent when using conventional, context-independent approaches.

引用

页码：1872 / 1886

页数：15

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