N-苄基-N-(X-2-羟基苄基)-N'-苯基脲和硫脲类化合物的合成及构效关系研究进展作为抗肿瘤药物。
Synthesis and structure-activity relationships of N-benzyl-N-(X-2-hydroxybenzyl)-N'-phenylureas and thioureas as antitumor agents.
机构信息
State Key Laboratory of Pollution Control and Resource Reuse, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
出版信息
Bioorg Med Chem. 2010 Jan 1;18(1):305-13. doi: 10.1016/j.bmc.2009.10.054. Epub 2009 Oct 31.
Two series of novel N-benzyl-N-(X-2-hydroxybenzyl)-N'-phenylureas and thioureas (1a-18a; 1b-18b) as potential EGFR and HER-2 kinase inhibitors have been discovered. These compounds displayed good EGFR and HER-2 inhibitory activity and the SARs are also been studied. Especially compound 7b demonstrated significant EGFR and HER-2 inhibitory activity (IC(50)=0.08 microM for EGFR and IC(50)=0.35 microM for HER-2). Docking simulation was performed to position compound 7b into the EGFR active site to determine the probable binding conformation and antiproliferative assay results indicating that these series of urea and thioureas own high antiproliferative activity against MCF-7. Above all, thiourea 7b would be a potential anticancer agent deserves further research.
已经发现了两个系列的新型 N-苄基-N-(X-2-羟基苄基)-N'-苯基脲和硫脲（1a-18a；1b-18b），作为潜在的 EGFR 和 HER-2 激酶抑制剂。这些化合物表现出良好的 EGFR 和 HER-2 抑制活性，并且还研究了 SAR。特别是化合物 7b 表现出显著的 EGFR 和 HER-2 抑制活性（IC50=0.08μM 对 EGFR 和 IC50=0.35μM 对 HER-2）。进行了对接模拟，将化合物 7b 定位到 EGFR 的活性部位，以确定可能的结合构象和抗增殖测定结果表明，这些脲和硫脲系列对 MCF-7 具有高的抗增殖活性。最重要的是，硫脲 7b 可能是一种有前途的抗癌药物，值得进一步研究。
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