Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors
Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors
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DOI：
10.1016/j.ejmech.2009.12.026
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发表时间：
2010-03-01
影响因子：
6.7
通讯作者：
El-Metwally, Amira M.
中科院分区：
文献类型：
--
作者：
Ibrahim, Diaa A.;El-Metwally, Amira M.
设计并合成了2，4，5，6-四取代的嘧啶细胞周期蛋白依赖性激酶(CDK2)抑制剂的新衍生物。我们建立了一个建议的嘧啶类化合物的资料库，并通过使用药效团和对接技术进行了选择。由于对接结构与蛋白质的相互作用，我们对所建议的化合物进行了修饰，以达到最佳匹配。新合成的化合物显示出强大的和选择性的CDK2抑制活性，并抑制体外培养的人肿瘤细胞的细胞增殖。报道了这些2，4，5，6-四取代嘧啶类化合物的设计、合成和生物活性。(C)2009年爱思唯尔·马森公司。版权所有。
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. (C) 2009 Elsevier Masson SAS. All rights reserved.