Abstract
A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38 alpha MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38 alpha enzyme.
MeSH terms
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Amides / chemistry
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Animals
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Crystallography, X-Ray
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Female
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 14 / metabolism*
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Models, Molecular
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Molecular Structure
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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 / chemistry*
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Structure-Activity Relationship
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Triazines / chemical synthesis*
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Triazines / chemistry
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Triazines / pharmacology*
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Amides
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Protein Kinase Inhibitors
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Pyrroles
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Triazines
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Tumor Necrosis Factor-alpha
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Mitogen-Activated Protein Kinase 14