Structural pairwise comparisons of HLM stability of phenyl derivatives: Introduction of the Pfizer metabolism index (PMI) and metabolism-lipophilicity efficiency (MLE)

被引：48

作者：

Lewis, Mark L. ^{[1
]}

Cucurull-Sanchez, Lourdes ^{[1
]}

机构：

[1] Pfizer PGRD, Dept Pharmacokinet Dynam & Metab, Sandwich CT13 9NJ, Kent, England

来源：

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN | 2009年 / 23卷 / 02期

关键词：

Pairwise comparison; Human liver microsome; Pfizer metabolism index; Metabolism-lipophilicity efficiency; Topliss analysis; PROTEIN;

D O I：

10.1007/s10822-008-9242-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Data mining by pairwise comparison of over 150,000 human liver microsome (HLM) intrinsic clearance values stored within the internal Pfizer database has been performed by an automated tool. Systematic probability tables of specific structural changes on the intrinsic clearance of phenyl derivatives have been generated. From these data two new parameters, the Pfizer Metabolism Index (PMI) and Metabolism-Lipophilicity Efficiency (MLE) are introduced for each fragment. The findings are applied to a Topliss style analysis that focuses on metabolic stability.

引用

页码：97 / 103

页数：7

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