2-aminopyrimidinones and their 6-aza-analogs

In order to find the new potent CK2 inhibitors 60 derivatives of 2-aminopyrimidinones and their 6-aza-substituted analogs were synthesized and tested in vitro. Among them, the most efficient inhibitor 2-hydroxy-5-[4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidin-2-ylamino]benzoic acid was identified (IC₅₀ = 1.1 μM). The structure-activity relationship study of newly synthesized derivatives was carried out and their binding mode with adenosine triphosphate-acceptor site of CK2 was proposed (Fig. 1). 

Figure 1. 2-aminopyrimidinone inhibitor of FGFR1.

• M.O. Chekanov, O.V. Ostrynska, S.S. Tarnavskyi, A.R. Synyugin, N.V. Briukhovetska, V.G. Bdzhola, A.E. Pashenko, A.A. Fokin, S.M. Yarmoluk. (2014) Design, synthesis and biological evaluation of 2-aminopyrimidinones and their 6-aza-analogs as a new class of CK2 inhibitors. J Enzyme Inhib Med Chem 29(5):639-646.