Abstract
We have identified a novel series of ring-fused pyrazole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <1nM) as well as excellent cellular activity against mixed lymphocyte reaction (MLR) (IC(50)s <1nM).
Copyright 2009 Elsevier Ltd. All rights reserved.
MeSH terms
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Adenosine Triphosphate / chemistry
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Binding Sites
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Computer Simulation
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Crystallography, X-Ray
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Hydrogen Bonding
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
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Lymphocytes / drug effects
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Lymphocytes / metabolism
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology
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Pyrroles / chemical synthesis
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Pyrroles / chemistry*
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Pyrroles / pharmacology
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Pyrroles
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Adenosine Triphosphate
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)