Second generation 4-(4-methyl-1H-indol-5-ylamino)-2-phenylthieno[2,3-b]pyridine-5-carbonitrile PKCθ inhibitors

Thieno[2,3-b]pyridine-5-carbonitrile 16 with a 4-methyl-5-indolylamine at C-4 and a 5-methoxy-2-(dimethylamino)-methylphenyl group at C-2 had an IC50 value of 16 nM for the inhibition of PKCθ. While moderate inhibition of PKCδ was also observed (IC50 = 130 nM), 16 had IC50 values of greater than 5 μM against Lyn and other members of the Src kinase family.

Graphical abstractThe 4-(4-methyl-1H-indol-5-ylamino)thieno[2,3-b]pyridine-5-carbonitrile 16 had an IC50 of 16 nM for the inhibition of PKCθ activity.Figure optionsDownload full-size imageDownload as PowerPoint slide