Abstract
We earlier reported that 3-pyridinecarbonitriiles with a 4-methylindolyl-5-amino group at C-4 and a phenyl group at C-5 were inhibitors of PKCtheta. Keeping the group at C-4 of the pyridine core constant, we varied the water solubilizing group on the phenyl ring at C-5 and then replaced the C-5 phenyl ring with several monocyclic heteroaryl rings, including furan, thiophene and pyridine. Analog 6e with a 4-methylindol-5-ylamino group at C-4 and a 5-[(4-methylpiperazin-1-yl)methyl]-2-furyl group C-5 had an IC50 value of 4.5 nM for the inhibition of PKCtheta.
MeSH terms
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Animals
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Inhibitory Concentration 50
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / genetics
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Isoenzymes / metabolism*
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Mice
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Mice, Knockout
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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 / genetics
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Protein Kinase C / metabolism*
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Protein Kinase C-theta
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology*
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Pyridines / chemistry*
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Pyridines / pharmacology*
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Structure-Activity Relationship
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism
Substances
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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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Prkcq protein, mouse
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Protein Kinase C
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Protein Kinase C-theta