Abstract
A novel series of pyrimidine-benzenesulfonamide derivatives as potential cyclin-dependent kinase 2 inhibitors were designed depending upon the molecular docking simulation study. This study was preceded by modification and optimization of the lead compound 4-(2-amino-4-methylthiazol-5-yl)-N-(3-nitrophenyl) pyrimidin-2-amine. The target proposed compounds were synthesized using the derivative 6-(3,4-dimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (1) as a key starting compound. Some of the synthesized derivatives were selected as representative examples to evaluate their anti-proliferative activity against cultured human Hela cell line using doxorubicin as a reference drug and the results obtained were correlated with the data of molecular modeling simulation study. The structures of the novel derivatives were confirmed on the bases of micro-analytical and spectral data.
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This study was supported by the National Research Centre, Dokki, Cairo, Egypt.
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Fathalla, O.A.EF.M., Ismail, M.A.H., Anwar, M.M. et al. Novel 2-thiopyrimidine derivatives as CDK2 inhibitors: molecular modeling, synthesis, and anti-tumor activity evaluation. Med Chem Res 22, 659–673 (2013). https://doi.org/10.1007/s00044-012-0051-9
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DOI: https://doi.org/10.1007/s00044-012-0051-9