Synthesis and biological evaluation of novel amino-substituted derivatives of pyrido[2,3-d]pyrimidine as inhibitors of protein kinase CK2

• Published in: Biopolimery i kletka 2017-01, Vol.33 (5), p.367-378
• Main Authors: Zinchenko, A. N., Muzychka, L. V., Smolii, O. B., Bdzhola, V. G., Protopopov, M. V., Yarmoluk, S. M.
• Format: Article
• Language: English
• Subjects: Casein kinase II; Kinases; Protein kinase C; Proteins; Pyrimidines
• ISSN: 0233-7657; 1993-6842
• DOI: 10.7124/bc.000960

Aim. A search for human protein kinase CK2 inhibitors in a series of new amino-substituted pyrido[2,3-d]pyrimidine derivatives. Methods. Organic synthesis, analytical and spectral methods, molecular docking, in vitro biochemical testing. Results. Synthesis of new pyrido[2,3-d]pyrimidine derivatives with various aminogroups in positions 4 and 6 of the heterocycle was developed. Two compounds inhibiting kinase CK2 in micromolar concentrations were found among these derivatives. Conclusion. New pyrido[2,3-d]pyrimidin-7-ones containing aminogroups in positions 4 and 6 of heterocyclic system and new 4-amino-substituted pyrido[2,3-d]pyrimidin-7-amine derivatives have been synthesized. The inhibition activity of new pyrido[2,3-d]pyrimidines has been examined and the optimization modes have been suggested. Methyl-2-[(7-aminopyrido[2,3-d]pyrimidine-6-yl)amino]benzoate and N-(4-anilino-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-yl)-3,4-dimethoxy- benzamide were found to inhibit protein kinase CK2 at IC50 of 6 and 19.5 μM, respectively.