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, 2014/10;29(5):639-46.
Chekanov MO[1], Ostrynska OV, Tarnavskyi SS, Synyugin AR, Briukhovetska NV, Bdzhola VG, Pashenko AE, Fokin AA, Yarmoluk SM
Affiliations
PMID: 24090425DOI: 10.3109/14756366.2013.837898
Impact factor: 5.756
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
MeSH terms
Aminosalicylic Acids; Aza Compounds; Casein Kinase II; Dose-Response Relationship, Drug; Drug Design; Humans; Molecular Structure; Protein Kinase Inhibitors; Pyrimidinones; Structure-Activity Relationship
More resources
EndNote: Download