Discovery of 2,6-disubstituted pyrazine derivatives as inhibitors of CK2 and PIM kinases

Abstract The design and synthesis of a novel series of 2,6-disubstituted pyrazine derivatives as CK2 kinase inhibitors is described. Structure-guided optimization of a 5-substituted-3-thiophene carboxylic acid screening hit ( 3a ) led to the development of a lead compound ( 12b ), which shows inhibition in both enzymatic and cellular assays. Subsequent design and hybridization efforts also led to the unexpected identification of analogs with potent PIM kinase activity ( 14f ).