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基于吲唑的二芳基脲衍生物的合成及其对肿瘤细胞系的抗增殖活性。

Synthesis of indazole based diarylurea derivatives and their antiproliferative activity against tumor cell lines.

机构信息

Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Wen Hua Xi Rd, Jinan 250012, China.

出版信息

Bioorg Med Chem Lett. 2013 Apr 1;23(7):1989-92. doi: 10.1016/j.bmcl.2013.02.034. Epub 2013 Feb 15.

Abstract

New series of indazole based diarylureas were synthesized and their anticancer activity against cancer cells H460, A549, OS-RC-2, HT-29, Lovo, HepG2, Bel-7402, SGC-7901 and MDA-MB-231 were examined. These derivatives of diarylureas, except azaindazole based diarylureas 5f, 5l and 5m, showed superior or similar activity against most of these selected cancer cell lines to the reference compound sorafenib. The effect of substituents on the indazole ring was also investigated. Derivatives with trifluoromenthy or halogen substituent on the indazole ring showed higher activity against the selected cancer cell lines than sorafenib. The acute toxicity assay showed that compounds 5a, 5b and 5i possessed lower toxicity than sorafenib. Compound 5i with 4-(trifluoromenthy)-1H-indazole and 4-(trifluoromenthy) benzene moieties exhibited the most potent anticancer activity.

摘要

新系列的吲唑基二芳基脲被合成,并对 H460、A549、OS-RC-2、HT-29、Lovo、HepG2、Bel-7402、SGC-7901 和 MDA-MB-231 癌细胞进行了抗癌活性测试。这些二芳基脲的衍生物,除了吲唑基二芳基脲 5f、5l 和 5m 外,对大多数选定的癌细胞系的活性均优于或与参考化合物索拉非尼相当。还研究了吲唑环上取代基的影响。吲唑环上带有三氟甲基或卤素取代基的衍生物对选定的癌细胞系的活性高于索拉非尼。急性毒性试验表明,化合物 5a、5b 和 5i 的毒性低于索拉非尼。带有 4-(三氟甲基)-1H-吲唑和 4-(三氟甲基)苯部分的化合物 5i 表现出最强的抗癌活性。

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