First generation 5-vinyl-3-pyridinecarbonitrile PKCθ inhibitors

A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCθ inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCθ inhibitor with good selectivity over PKCδ.

The synthesis of a series of 5-vinyl-3-pyridinecarbonitriles resulted in a potent PKCθ inhibitor 23e, which had an IC50 value of 4.7 nM for the inhibition of PKCθ with 11-fold selectivity over PKCδ.Figure optionsDownload as PowerPoint slide