Two series of diaryl urea derivatives, 6a–k and 7a–n, were synthesized. All the newly synthesized compounds were tested against the NCI (US) cancer cell lines via SRB assay. The p-chloro-m-trifluoromethyl phenyl derivatives 6e–g and 7e–g showed the most potent cytotoxic activity with a GI₅₀ value range of 1.2–15.9 µM. Furthermore, the p-fluorobenzyloxy diaryl urea derivative 7g revealed the most potent cytotoxicity against eight cancer cell lines in the MTT assay with IC₅₀ values below 5 µM. Compounds 6a–k and 7a–n were tested for their vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitory activities. The p-chloro-m-trifluoromethyl diaryl urea benzyloxy derivatives 7e–i and the p-methoxydiaryl urea benzyloxy derivatives 7k, 7l, and 7n were found to be the most active compounds as VEGFR-2 inhibitors in the benzyloxy series 7, with an IC₅₀ range of 0.09–4.15 µM. In the 2-oxo-2-phenylethoxy series 6, compounds 6e–g and 6i were reported with IC₅₀ values of 0.94, 0.54, 2.71, and 4.81 µM, respectively. Moreover, compounds 7e and 7g induced apoptosis, causing cell cycle arrest in the G2/M phase. In addition, 7g showed an antimigratory effect in A-375 cells and inhibited the VEGFR-2 expression in an immunohistofluorescence study. Molecular docking simulations on VEGFR-2 as well as ADME properties prediction were also performed.

中文翻译：

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作为 VEGFR-2 抑制剂的新型 2-oxo-2-phenylethoxy 和苄氧基二芳基脲杂化物：设计、合成和抗癌评估

合成了两个系列的二芳基脲衍生物，6a-k和7a-n。所有新合成的化合物都通过 SRB 测定法针对 NCI（美国）癌细胞系进行了测试。对氯间三氟甲基苯基衍生物6e–g和7e–g显示出最强的细胞毒活性，GI ₅₀值范围为 1.2–15.9 µM 。此外，7g对氟苄氧基二芳基脲衍生物在 MTT 测定中显示出对八种癌细胞系最有效的细胞毒性，IC ₅₀值低于 5 µM。化合物6a–k和7a–n测试了它们的血管内皮生长因子受体 2 (VEGFR-2) 激酶抑制活性。发现对氯间三氟甲基二芳基脲苄氧基衍生物7e –i和对甲氧基二芳基脲苄氧基衍生物7k、7l和7n是苄氧基系列7中作为 VEGFR-2 抑制剂最具活性的化合物，具有IC ₅₀范围为 0.09–4.15 µM。在 2-oxo-2-phenylethoxy 系列6中，化合物6e–g和6i的 IC ₅₀值分别为 0.94、0.54、2.71 和 4.81 µM。此外，化合物7e和7g诱导细胞凋亡，导致细胞周期停滞在G2/M期。此外，7g在 A-375 细胞中显示出抗迁移作用，并在免疫组织荧光研究中抑制 VEGFR-2 表达。还进行了 VEGFR-2 的分子对接模拟以及 ADME 特性预测。