Research Area · Protein Kinase CK2

2-Aminopyrimidinones and Their 6-Aza Analogues

A related series of ATP-competitive CK2 inhibitors developed through synthesis, biological evaluation and structure–activity analysis.

2-aminopyrimidinone inhibitor bound within the ATP-binding pocket of protein kinase CK2

To identify novel protein kinase CK2 inhibitors, 60 derivatives of 2-aminopyrimidinones and their 6-aza-substituted analogues were synthesized and evaluated in vitro. The most potent inhibitor, 2-hydroxy-5-[4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidin-2-ylamino]benzoic acid, inhibited protein kinase CK2 with an IC50 value of 1.1 μM. The relationship between the inhibitory activity of the 2-aminopyrimidinone derivatives and their chemical structures was investigated, and a binding mode for compounds of this class within the active site of protein kinase CK2 was proposed (Figure 1).

2-Aminopyrimidinone inhibitor of protein kinase CK2 and its proposed binding mode
Figure 1. 2-Aminopyrimidinone inhibitor of protein kinase CK2.

Publication

Chekanov MO, Ostrynska OV, Tarnavskyi SS, Synyugin AR, Briukhovetska NV, Bdzhola VG, Pashenko AE, Fokin AA, Yarmoluk SM. Design, synthesis and biological evaluation of 2-aminopyrimidinones and their 6-aza-analogs as a new class of CK2 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2014;29(5):639–646.