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

Bioorg Med Chem Lett. 2018 May 1;28(8):1336-1341. doi: 10.1016/j.bmcl.2018.03.018. Epub 2018 Mar 7.


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).

Keywords: 2,6-Disubstituted pyrazine; Cancer; Dual CK2 and PIM kinase inhibitors.

MeSH terms

  • Casein Kinase II / antagonists & inhibitors*
  • Cell Line, Tumor
  • Drug Design
  • Humans
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry
  • Pyrazines / pharmacokinetics
  • Pyrazines / pharmacology*
  • Structure-Activity Relationship


  • Protein Kinase Inhibitors
  • Pyrazines
  • Casein Kinase II
  • PIM1 protein, human
  • Proto-Oncogene Proteins c-pim-1