Abstract
A series of 5,7-disubstituted quinazolines, bearing 4-heteroaryl substituents such as 2-pyridinylamine or 2-pyrazinylamine, has been synthetised and evaluated as c-Src kinase inhibitors. Highly potent inhibition, high selectivity and physical properties suitable for oral dosing were achieved within this series: 23d and 42 were identified as sub-0.1muM inhibitors in a c-Src-driven cell proliferation assay and displayed adequate rat pharmacokinetics after oral administration.
MeSH terms
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Aniline Compounds / chemical synthesis
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Aniline Compounds / pharmacology
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Animals
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CSK Tyrosine-Protein Kinase
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Cell Division
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Heterocyclic Compounds / chemical synthesis
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Heterocyclic Compounds / pharmacokinetics
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Heterocyclic Compounds / pharmacology
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Isomerism
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Kinetics
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Models, Molecular
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Quinazolines / chemical synthesis
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Quinazolines / pharmacology
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Rats
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src-Family Kinases
Substances
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Aniline Compounds
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Enzyme Inhibitors
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Heterocyclic Compounds
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Quinazolines
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Protein-Tyrosine Kinases
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CSK Tyrosine-Protein Kinase
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src-Family Kinases