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

• Date: 2017
• Main Authors: Zinchenko, A.N., Muzychka, L.V., Smolii, O.B., Bdzhola, V.G., Protopopov, M.V., Yarmoluk, S.M.
• Format: Article
• Language: English
• Published: Інститут молекулярної біології і генетики НАН України 2017
• Series: Вiopolymers and Cell
• Subjects: Bioorganic Chemistry
• Online Access: https://nasplib.isofts.kiev.ua/handle/123456789/152990
• Journal Title: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Cite this: Synthesis and biological evaluation of novel amino-substituted derivatives of pyrido[2,3-d]pyrimidine as inhibitors of protein kinase CK2 / A.N. Zinchenko, L.V. Muzychka, O.B. Smolii, V.G. Bdzhola, M.V. Protopopov, S.M. Yarmoluk // Вiopolymers and Cell. — 2017. — Т. 33, № 5. — С. 367-378. — Бібліогр.: 41 назв. — англ.

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.