Abstract
A series of novel compound libraries inhibiting interleukin-2 inducible T cell kinase (ITK) were designed, synthesized and evaluated. In the first design cycle two library scaffolds were identified showing low micromolar inhibition of ITK. Further iterative design cycles including crystal structure information of ITK and structurally related kinases led to the identification of indolylindazole and indolylpyrazolopyridine compounds with low nanomolar ITK inhibition.
Copyright © 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Crystallography, X-Ray
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Drug Design*
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Humans
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Indazoles / pharmacology
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Interleukin-2
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Protein Kinase Inhibitors / analogs & derivatives
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Pyridines / pharmacology
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Small Molecule Libraries*
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Structure-Activity Relationship
Substances
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Indazoles
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Interleukin-2
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Protein Kinase Inhibitors
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Pyridines
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Small Molecule Libraries
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Protein-Tyrosine Kinases
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emt protein-tyrosine kinase