A practical drug discovery project at the undergraduate level.
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 (PI3Kδ) 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 ≥tenfold, respectively.
School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: jonathan.fray@nottingham.ac.uk.
M Jonathan
MJ
Fray
Simon J F
SJ
Macdonald
Ian R
IR
Baldwin
Nick
N
Barton
Jack
J
Brown
Ian B
IB
Campbell
Ian
I
Churcher
Diane M
DM
Coe
Anthony W J
AW
Cooper
Andrew P
AP
Craven
Gail
G
Fisher
Graham G A
GG
Inglis
Henry A
HA
Kelly
John
J
Liddle
Aoife C
AC
Maxwell
Vipulkumar K
VK
Patel
Stephen
S
Swanson
Natalie
N
Wellaway
D002626:Chemistry, Pharmaceutical / Q000193:education*; D003479:Curriculum; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004345:Drug Industry / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012995:Solubility
D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors