Divergent synthesis of kinase inhibitor derivatives, leading to discovery of selective Gck inhibitors
We achieved the divergent synthesis of the potent kinase inhibitor BAY 61-3606 (1) along with 27 derivatives by conjugating imidazo[1,2-c]pyrimidine and indole ring structures with various aromatic (including pyridine) derivatives through palladium-catalyzed cross-coupling reactions. Inhibition assays targeting spleen tyrosine kinase (Syk) and germinal center kinase (Gck, MAP4K2) revealed that several of the synthesized compounds BAY-61-3606 demonstrated selective inhibition of Gck.