کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
443788 692768 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Calculation and application of activity discriminants in lead optimization
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
Calculation and application of activity discriminants in lead optimization
چکیده انگلیسی

We present a technique for computing activity discriminants of in vitro (pharmacological, DMPK, and safety) assays and the application to the prediction of in vitro activities of proposed synthetic targets during the lead optimization phase of drug discovery projects. This technique emulates how medicinal chemists perform SAR analysis and activity prediction. The activity discriminants that are functions of 6 commonly used medicinal chemistry descriptors can be interpreted easily by medicinal chemists. Further, visualization with Spotfire allows medicinal chemists to analyze how the query molecule is related to compounds tested previously, and to evaluate easily the relevance of the activity discriminants to the activities of the query molecule. Validation with all compounds synthesized and tested in AstraZeneca Wilmington since 2006 demonstrates that this approach is useful for prioritizing new synthetic targets for synthesis.

Figure optionsDownload high-quality image (126 K)Download as PowerPoint slideResearch highlights▶ Predict activities of in vitro (pharmacological, DMPK, and safety) assays. ▶ Emulate how medicinal chemists perform SAR analysis and activity prediction. ▶ Useful for prioritizing new molecules for synthesis during the lead optimization phase of drug discovery projects.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 29, Issue 3, November 2010, Pages 372–381
نویسندگان
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