The diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Most of the target compounds demonstrate significant antiproliferative effects on all the selective cancer cell lines. The calculated IC₅₀ values were reported. The target compound 1-(4-chlorophenyl)-3-{4-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy}phenyl}urea (7u) demonstrated the most potent inhibitory activity (IC₅₀ = 2.39 ± 0.10 μM for A549 and IC₅₀ = 3.90 ± 0.33 μM for HCT-116), comparable to the positive-control sorafenib (IC₅₀ = 2.12 ± 0.18 μM for A549 and IC₅₀ = 2.25 ± 0.71 μM for HCT-116). Conclusively, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as the new anticancer agents were discovered, and could be used as the potential BRAF inhibitors for further research.

中文翻译：

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新型抗癌剂 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea 衍生物的合成和生物学评价。

二芳基脲是药物化学中非常重要的片段。通过计算机辅助设计，设计合成了1-芳基-3-[4-(吡啶-2-基甲氧基)苯基]脲衍生物，并评价其对A549、HCT-116、PC-3癌的抗增殖活性通过使用 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 比色法测定体外细胞系和 HL7702 人正常肝细胞系。大多数目标化合物对所有选择性癌细胞系都表现出显着的抗增殖作用。报告计算出的IC ₅₀值。目标化合物1-(4-氯苯基)-3-{4-{[3-甲基-4-(2,2,2-三氟乙氧基)吡啶-2-基]甲氧基}苯基}脲( 7u )有效的抑制活性（IC ₅₀ = 2.39 ± 0.10 μM A549 和 IC ₅₀  = 3.90 ± 0.33 μM 对于 HCT-116），与阳性对照索拉非尼相当（IC ₅₀  = 2.12 ± 0.18 μM 对于 A549 和 IC ₅₀  = 2.25 ± 0.71 μM 对于 HCT-116 ）。最终，发现了 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea 衍生物作为新的抗癌剂，可作为潜在的 BRAF 抑制剂进行进一步研究。