Abstract
The synthesis and structure-activity relationships (SAR) of p38alpha MAP kinase inhibitors based on heterobicyclic scaffolds are described. This effort led to the identification of compound (21) as a potent inhibitor of p38alpha MAP kinase with good cellular potency toward the inhibition of TNF-alpha production. X-ray co-crystallography of an oxalamide analog (24) bound to unphosphorylated p38alpha is also disclosed.
MeSH terms
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Bridged Bicyclo Compounds / chemical synthesis*
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Bridged Bicyclo Compounds / chemistry
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Bridged Bicyclo Compounds / pharmacology*
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Crystallography, X-Ray
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Heterocyclic Compounds / chemical synthesis*
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Heterocyclic Compounds / chemistry
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Heterocyclic Compounds / pharmacology*
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Models, Molecular
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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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Structure-Activity Relationship
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Substances
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Bridged Bicyclo Compounds
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Heterocyclic Compounds
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Protein Kinase Inhibitors
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p38 Mitogen-Activated Protein Kinases