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.
2010 Elsevier Ltd. All rights reserved.
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases
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Cell Line, Tumor
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Crystallography, X-Ray
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Humans
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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
Substances
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Protein Kinase Inhibitors
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3-Phosphoinositide-Dependent Protein Kinases
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PDPK1 protein, human
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Protein Serine-Threonine Kinases