A practical drug discovery project at the undergraduate level

作者:Fray M Jonathan*; Macdonald Simon J F; Baldwin Ian R; Barton Nick; Brown Jack; Campbell Ian B; Churcher Ian; Coe Diane M; Cooper Anthony W J; Craven Andrew P; Fisher Gail; Inglis Graham G A; Kelly Henry A; Liddle John; Maxwell Aoife C; Patel Vipulkumar K; Swanson Stephen; Wellaway Natalie
来源:Drug Discovery Today, 2013, 18(23-24): 1158-1172.
DOI:10.1016/j.drudis.2013.09.004

摘要

In this article, we describe a practical drug discovery project for third-year undergraduates. No previous knowledge of medicinal chemistry is assumed. Initial lecture workshops cover the basic principles; then students, in teams, seek to improve the profile of a weakly potent, insoluble phosphatidylinositide 3-kinase delta (PI3K delta) inhibitor (1) through compound array design, molecular modelling, screening data analysis and the synthesis of target compounds in the laboratory. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. In total, 48 target compounds were prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and %26gt;= tenfold, respectively.

  • 出版日期2013-12