Optimization of 5-phenyl-3-pyridinecarbonitriles as PKCθ inhibitors

The key intermediate, 4-chloro-5-iodo-3-pyridinecarbonitrile, allowed for ready optimization of the PKCθ 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 IC50 value of 7.4 nM for the inhibition of PKCθ.

Graphical abstractAnalog 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 IC50 value of 7.4 nM for the inhibition of PKCθ.Figure optionsDownload full-size imageDownload as PowerPoint slide