National Organization for Drug Control & Research, PO Box 29, Cairo, Gizaa 112313, Egypt.
Eur J Med Chem. 2010 Mar;45(3):1158-66. doi: 10.1016/j.ejmech.2009.12.026. Epub 2009 Dec 21.
Novel derivatives of 2,4,5,6-tetrasubstituted pyrimidine cyclin-dependent kinase (CDK2) inhibitors was designed and synthesized. We built a library of proposed pyrimidine derivatives and by using pharmacophore and docking techniques we made our selections. We modified the proposed compounds due to the interaction of docked structures with the protein to achieve the best fit. The newly synthesized compounds showed potent and selective CDK2 inhibitory activities and inhibited in-vitro cellular proliferation in cultured human tumor cells. The design, synthesis and biological evaluation of these 2,4,5,6-tetrasubstituted pyrimidine derivatives are reported.
新型 2,4,5,6-四取代嘧啶细胞周期蛋白依赖性激酶（CDK2）抑制剂衍生物的设计与合成。我们构建了一个嘧啶衍生物库，并通过药效团和对接技术进行了选择。我们对所提出的化合物进行了修改，以适应与蛋白质的相互作用，以达到最佳的拟合效果。新合成的化合物表现出强大的、选择性的 CDK2 抑制活性，并抑制体外培养的人类肿瘤细胞的增殖。报告了这些 2,4,5,6-四取代嘧啶衍生物的设计、合成和生物评价。
