Abstract
A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were prepared. Structure-activity relationships, selectivity and cell activity are reported for this series. Compound 2, a potent and selective antagonist of Itk, inhibited anti-CD3 antibody induced IL-2 production in vivo in mice.
MeSH terms
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Administration, Oral
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Animals
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Benzimidazoles / administration & dosage*
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry*
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Benzimidazoles / pharmacology
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CD3 Complex / biosynthesis
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Humans
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Inhibitory Concentration 50
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Models, Chemical
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Protein-Tyrosine Kinases / chemistry*
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Structure-Activity Relationship
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T-Lymphocytes / cytology
Substances
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Benzimidazoles
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CD3 Complex
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase