Abstract
2-Arylamino-4-aryl-pyrimidines were found to be potent inhibitors of PAK1 kinase. The synthesis and SAR are described. The incorporation of a bromide at the 5-position of the pyrimidine core and in combination with a 1,2-dimethylpiperazine pendant domain yielded a lead compound with potent PAK1 inhibition and anti-proliferative activity in various colon cancer cell lines.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Aniline Compounds / chemical synthesis*
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Aniline Compounds / chemistry
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Aniline Compounds / toxicity
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Humans
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Protein Binding
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / toxicity
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Pyrimidinones / chemical synthesis*
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Pyrimidinones / chemistry
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Pyrimidinones / toxicity
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Structure-Activity Relationship
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p21-Activated Kinases / antagonists & inhibitors*
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p21-Activated Kinases / metabolism
Substances
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Aniline Compounds
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Protein Kinase Inhibitors
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Pyrimidinones
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p21-Activated Kinases