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. 2014 Oct;29(5):639-46. doi: 10.3109/14756366.2013.837898.
Maksym O Chekanov  1 ,  Olga V Ostrynska ,  Sergii S Tarnavskyi ,  Anatoliy R Synyugin ,  Nadiia V Briukhovetska ,  Volodymyr G Bdzhola ,  Alexander E Pashenko ,  Andrey A Fokin ,  Sergiy M Yarmoluk
Affiliations
  • 1. Institute of Molecular Biology and Genetics, NAS of Ukraine , Kyiv , Ukraine .
PMID: 24090425 DOI: 10.3109/14756366.2013.837898
Abstract

In order to find the new potent CK2 inhibitors the 60 derivatives of 2-aminopyrimidinone and their 6-aza-substituted analogs were synthesized and tested in vitro. Among them, the most efficient inhibitor 2-hydroxy-5-[4-(4-methoxyphehyl)-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.

Keywords
Aza-pyrimidinones; CK2 inhibitors; chemical optimization; combinatorial synthesis; molecular docking; pyrimidinones; receptor-based virtual screening.
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