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.

Graphical abstractA series of 2-alkenylamide thieno[2,3-b]pyridine inhibitors of PKCθ is described. SAR studies led to compound 8 which has excellent selectivity over a variety of PKC isoforms.Figure optionsDownload full-size imageDownload as PowerPoint slide