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A practical drug discovery project at the undergraduate level

Fray, Michael J.; 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

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Authors

Michael J. Fray

Simon J.F. Macdonald

Ian R. Baldwin

Nick Barton

Jack Brown

Ian B. Campbell

Ian Churcher

Diane M. Coe

Anthony W.J. Cooper

Andrew P. Craven

Gail Fisher

Graham G.A. Inglis

Henry A. Kelly

John Liddle

Aoife C. Maxwell

Vipulkumar K. Patel

Stephen Swanson

Natalie Wellaway



Abstract

A practical drug discovery project for third-year undergraduates is described. No previous knowledge of medicinal chemistry is assumed. Initial lecture-workshops cover the basic principles; then students are asked to improve the profile of a weakly potent, poorly soluble PI3K? inhibitor (1). Compound array design, molecular modelling and screening data analysis are followed by laboratory work in which each student, as part of a team, attempts to synthesise at least two target compounds. 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. Forty-eight target compounds have been 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 ?10-fold, respectively.

Journal Article Type Article
Publication Date Dec 1, 2013
Deposit Date Jul 23, 2014
Publicly Available Date Jul 23, 2014
Journal Drug Discovery Today
Print ISSN 1359-6446
Electronic ISSN 1359-6446
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 18
Issue 23-24
DOI https://doi.org/10.1016/j.drudis.2013.09.004
Keywords undergraduate research project, asthma, kinase, PI3K delta, thienopyrimidines
Public URL https://nottingham-repository.worktribe.com/output/1000499
Publisher URL http://www.sciencedirect.com/science/article/pii/S1359644613002924
Additional Information NOTICE: this is the author’s version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 18(23-24), (2013), doi: 10.1016/j.drudis.2013.09.004

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