Li Huan-Qiu, Lv Peng-Cheng, Yan Tao, Zhu Hai-Liang
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Anticancer Agents Med Chem. 2009 May;9(4):471-80. doi: 10.2174/1871520610909040471.
Within the past ten years, a huge volume of research on the synthesis, structure-activity relationships (SAR), and anticancer activities of the urea derivatives was reported. Many aromatic urea derivatives such as N-phenyl-N'-(2-chloroethyl)ureas (CEUs) and benzoylureas (BUs) show good anticancer activity, and these compounds have mainly been proved to be tubulin ligands that inhibit the polymerization of tubulin. Heterocyclic urea derivatives play an important role in anticancer agents because of their good inhibitory activity against receptor tyrosine kinases (RTKs), raf kinases, protein tyrosine kinases (PTKs), and NADH oxidase, which play critical roles in many aspects of tumorigenesis. Thiourea derivatives are also of wide interest because of their diverse anticancer activity against various leukemias and solid tumors. In this review, the anticancer activity of the urea derivatives mentioned above is summarized in detail. It is hoped that increasing knowledge of the SAR and cellular processes underlying the antitumor-activity of urea derivatives will be beneficial to the rational design of new generation of urea anticancer drugs.
在过去十年中，报道了大量关于脲衍生物的合成、构效关系（SAR）和抗癌活性的研究。许多芳香族脲衍生物，如N-苯基-N'-(2-氯乙基)脲（CEU）和苯甲酰脲（BU），都表现出良好的抗癌活性，并且这些化合物主要被证明是微管蛋白配体，可抑制微管蛋白的聚合。杂环脲衍生物因其对受体酪氨酸激酶（RTK）、raf激酶、蛋白酪氨酸激酶（PTK）和NADH氧化酶具有良好的抑制活性，在抗癌药物中发挥着重要作用，这些酶在肿瘤发生的许多方面都起着关键作用。硫脲衍生物也因其对各种白血病和实体瘤具有多样的抗癌活性而备受关注。在本综述中，将详细总结上述脲衍生物的抗癌活性。希望增加对脲衍生物抗癌活性的构效关系和细胞过程的了解，将有助于新一代脲类抗癌药物的合理设计。
