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Title: 7-(Pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-based derivatives for kinase inhibition: Co-crystallisation studies with Aurora-A reveal distinct differences in the orientation of the pyrazole N1-substituent.
Authors: Bavetsias, V.
Pérez-Fuertes, Y.
McIntyre, Patrick J.
Atrash, B.
Kosmopoulou, M.
O'Fee, L.
Burke, R.
Sun, C.
Faisal, A.
Bush, K.
Avery, S.
Henley, A.
Raynaud, F. I.
Linardopoulos, S.
Bayliss, Richard
Blagg, J.
First Published: 6-Aug-2015
Publisher: Elsevier
Citation: Bioorganic & Medicinal Chemistry Letters 25 (2015) 4203–4209
Abstract: Introduction of a 1-benzyl-1H-pyrazol-4-yl moiety at C7 of the imidazo[4,5-b]pyridine scaffold provided 7a which inhibited a range of kinases including Aurora-A. Modification of the benzyl group in 7a, and subsequent co-crystallisation of the resulting analogues with Aurora-A indicated distinct differences in binding mode dependent upon the pyrazole N-substituent. Compounds 7a and 14d interact with the P-loop whereas 14a and 14b engage with Thr217 in the post-hinge region. These crystallographic insights provide options for the design of compounds interacting with the DFG motif or with Thr217.
DOI Link: 10.1016/j.bmcl.2015.08.003
ISSN: 0960-894X
eISSN: 1464-3405
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (
Description: Supplementary data associated with this article can be found, in the online version, at
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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