Abstract
The key intermediate, 4-chloro-5-iodo-3-pyridinecarbonitrile, allowed for ready optimization of the PKCtheta inhibitory activity of a series of 3-pyridinecarbonitriles. Analog 13b with a 4-methylindol-5-ylamino group at C-4 and a 4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl group at C-5 had an IC(50) value of 7.4nM for the inhibition of PKCtheta.
MeSH terms
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Animals
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Indoles / chemical synthesis
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Indoles / chemistry*
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Indoles / pharmacology
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / metabolism
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Mice
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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 / metabolism
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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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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / pharmacology
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Structure-Activity Relationship
Substances
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5-phenyl-3-pyridinecarbonitrile-(4-methylindol-5-ylamino)-5-4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl
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Indoles
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Isoenzymes
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Nitriles
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Protein Kinase Inhibitors
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Pyridines
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pyridine-3-carbonitrile
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Prkcq protein, mouse
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Protein Kinase C
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Protein Kinase C-theta