Design, synthesis and biological evaluation of 2-aminopyrimidinones and their 6-aza-analogs as a new class of CK2 inhibitors

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 29; no. 5; pp. 639 - 646
• Main Authors: Chekanov, Maksym O., Ostrynska, Olga V., Tarnavskyi, Sergii S., Synyugin, Anatoliy R., Briukhovetska, Nadiia V., Bdzhola, Volodymyr G., Pashenko, Alexander E., Fokin, Andrey A., Yarmoluk, Sergiy M.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.10.2014; Taylor & Francis
• Subjects: Aminosalicylic Acids - chemical synthesis; Aminosalicylic Acids - chemistry; Aminosalicylic Acids - pharmacology; Aza Compounds - chemical synthesis; Aza Compounds - chemistry; Aza Compounds - pharmacology; Aza-pyrimidinones; Casein Kinase II - antagonists & inhibitors; Casein Kinase II - metabolism; chemical optimization; CK2 inhibitors; combinatorial synthesis; Dose-Response Relationship, Drug; Drug Design; Humans; molecular docking; Molecular Structure; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; pyrimidinones; Pyrimidinones - chemical synthesis; Pyrimidinones - chemistry; Pyrimidinones - pharmacology; receptor-based virtual screening; Structure-Activity Relationship; CK2 inhibitors; molecular docking; combinatorial synthesis; chemical optimization; Aza-pyrimidinones; pyrimidinones; receptor-based virtual screening
• ISSN: 1475-6366; 1475-6374
• 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.