Abstract
A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.
MeSH terms
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Animals
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Asthma / pathology
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Cells, Cultured
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Hypersensitivity / pathology
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Jurkat Cells / drug effects
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Mice
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Pneumonia / pathology
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Structure-Activity Relationship
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Sulfides / chemical synthesis*
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Sulfides / pharmacology*
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Thiazoles / chemical synthesis*
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Thiazoles / pharmacology*
Substances
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Enzyme Inhibitors
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Sulfides
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Thiazoles
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase