High throughput solubility determination with application to selection of compounds for fragment screening

被引：18

作者：

Colclough, Nicola ^{[1
]}

Hunter, Alison ^{[1
]}

Kenny, Peter W. ^{[1
]}

Kittlety, Rod S. ^{[1
]}

Lobedan, Lynsey ^{[1
]}

Tam, Kin Y. ^{[1
]}

Timms, Mark A. ^{[1
]}

机构：

[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 13期

关键词：

solubility; physicochemical properties; UV/vis spectroscopy; automation; structure-property relationship; fragment screening; fragment-based drug discovery; screening library;

D O I：

10.1016/j.bmc.2008.05.021

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：

The development and application of a high throughput aqueous solubility assay is reported. Measurements for up to 637 compounds can be made in a fully automated experiment. Results from this assay were used to quantify risk of unacceptable solubility as a function of lipophilicity for neutral fragment-like compounds. Assessment of risk of unacceptable solubility was combined with experimental solubility measurement to select compounds for inclusion in a fragment-screening library. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6611 / 6616

页数：6

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