Structure-based optimization of potent PDK1 inhibitors

Bioorganic & Medicinal Chemistry Letters
Mauro AngioliniFabio Zuccotto

Abstract

In this Letter is described the structure-based design of potent dihydro-pyrazoloquinazolines as PDK1 inhibitors. Starting from low potency HTS hits with the aid of X-ray crystallography and modeling, a medicinal chemistry activity was carried out to improve potency versus PDK1 and selectivity versus CDK2 protein kinase.

References

Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Oct 31, 2008·ChemMedChem·Christian Peifer, Dario R Alessi

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Citations

Jul 23, 2011·Journal of Computer-aided Molecular Design·M Catherine JohnsonGordon Alton
Nov 2, 2011·Journal of Medicinal Chemistry·Sean T MurphyXiao-Hong Yu
Feb 9, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Xinyuan XuShaoyong Lu
Sep 10, 2018·Journal of Computer-aided Molecular Design·Noriyuki Yamaotsu, Shuichi Hirono
Feb 24, 2011·Journal of Medicinal Chemistry·Jesús R MedinaJeffrey M Axten

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