Abstract
Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified.
MeSH terms
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Adenosine Triphosphate / chemistry
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Administration, Oral
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry*
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Binding Sites
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CD3 Complex / chemistry
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Chemistry, Pharmaceutical / methods*
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Crystallography, X-Ray / methods
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Humans
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Inhibitory Concentration 50
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Microsomes, Liver / chemistry
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Microsomes, Liver / metabolism*
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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 / metabolism
Substances
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Benzimidazoles
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CD3 Complex
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Enzyme Inhibitors
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Adenosine Triphosphate
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benzimidazole
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase