2-Alkenylthieno[2,3-b]pyridine-5-carbonitriles: Potent and selective inhibitors of PKCθ

A series of 2-alkenyl thieno[2,3-b]pyridine inhibitors of PKCθ were synthesized as potential inflammatory modulators. This series led to the discovery of 2-alkenyl amides, which are exceptionally potent and selective inhibitors of PKCθ. Compound 8 has an IC50 of 3.8 nM against PKCθ and shows excellent selectivity over a variety of PKC isoforms.