Identification of novel protein kinase CK2 inhibitors among indazole derivatives.

Aim. To synthesize the novel purine bioisosteres -- indazole derivatives and evaluate inhibitory activity of these compounds towards CK2 in the in vitro system. Methods. Chemical synthesis, 1H and 13C NMR spectroscopy, LC-MS method, determination of residual enzyme activity using ATP consumption tests with a luciferase Kinase-Glo® luminescent kinase assay. Results. Known synthetic methods of indazole chemistry were originally applied to the synthesis of 3-aryl-indazole-7-carboxylic acids. Conditions of cross-coupling of 3-bromo-indazole derivatives with arylboronic acids were substantially improved. 3-aryl-indazole 5- and 7-carboxylic acids have shown IC50 in a range 3.1-6.5 μM in luciferase luminescent kinase assay. Conclusions. The synthesis of 3-aryl-indazole-7-carboxylic acids has been developed. Novel inhibitors of the protein kinase CK2 among indazole derivatives have been identified among the 3-aryl-indazole 5- and 7-carboxylic acids. It has been shown the crucial impact of carboxyl group on the inhibitory activity of studied compounds. [ABSTRACT FROM AUTHOR]