Abstract
A series of 2-alkenyl thieno[2,3-b]pyridine inhibitors of PKCtheta were synthesized as potential inflammatory modulators. This series led to the discovery of 2-alkenyl amides, which are exceptionally potent and selective inhibitors of PKCtheta. Compound 8 has an IC(50) of 3.8nM against PKCtheta and shows excellent selectivity over a variety of PKC isoforms.
MeSH terms
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Animals
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Combinatorial Chemistry Techniques
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Isoenzymes / antagonists & inhibitors*
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Mice
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Models, Chemical
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Molecular Structure
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacology*
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Protein Kinase C / antagonists & inhibitors*
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Protein Kinase C-theta
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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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Thiophenes / chemical synthesis*
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Thiophenes / chemistry
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Thiophenes / pharmacology*
Substances
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Isoenzymes
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Nitriles
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Protein Kinase Inhibitors
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Thiophenes
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Prkcq protein, mouse
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Protein Kinase C
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Protein Kinase C-theta