Abstract
A novel series of 5-aminopyrimidinyl quinazolines has been developed from anilino-quinazoline 1, which was identified in a high throughput screen for Aurora A. Introduction of the pyrimidine ring and optimisation of the substituents both on this ring and at the C7 position of the quinazoline led to the discovery of compounds that are highly specific Aurora kinase inhibitors. Co-crystallisation of one of these inhibitors with a fragment of Aurora A shows the importance of the benzamido group in achieving selectivity.
MeSH terms
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Aurora Kinases
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Benzamidines / chemistry
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Cell Line, Tumor
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Crystallography, X-Ray
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Humans
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Inhibitory Concentration 50
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Models, Molecular
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / classification*
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Tertiary
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Sensitivity and Specificity
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Benzamidines
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Protein Kinase Inhibitors
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Aurora Kinases
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Protein Serine-Threonine Kinases
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benzamidine