Key Laboratory of Pesticide Chemistry and Application, Ministry of Agriculture, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
Molecules. 2010 Jun 11;15(6):4267-82. doi: 10.3390/molecules15064267.
In order to find novel chitin synthesis inhibitors (CSIs) with good activity, benzoylphenylurea, a typical kind of CSIs, was chosen as the lead compound and 15 novel derivatives containing furan moieties were designed by converting the urea linkage of benzoylphenylureas into a semicarbazide and changing the aniline part into furoyl groups. The title compounds were synthesized by the reaction of substituted benzoyl isocyanates with 5-(substituted phenyl)-2-furoyl hydrazine, and the structures were confirmed by IR, (1)H-NMR, elemental analysis and single crystal X-ray diffraction analyses (compound E2). The bioassay results indicated that the title compounds exhibit good insecticidal activity, especially towards Plutella xylostella L., but had lower fungicidal activity. Inspiringly, the title compounds possessed obvious anticancer activity against human promyelocytic leukemic cell line (HL-60), and some of the title compounds also had activity against human hepatocellular carcinoma cell line (Bel-7402), human gastric carcinoma cell line (BGC-823), and human nasopharyngeal carcinoma cell line (KB). The results indicated that the linkage in the lead compounds was important to the bioactivity and spectra. The modification on the urea linkage is an effective strategy to discover new pesticide and drug candidates.
为了寻找具有良好活性的新型几丁质合成抑制剂（CSIs），选择苯甲酰基苯脲作为先导化合物，通过将苯甲酰基苯脲的脲键转化为氨基甲脒并将苯胺部分改为呋喃酰基，设计了 15 种新型含呋喃基的衍生物。通过取代的苯甲酰异氰酸酯与 5-（取代苯基）-2-呋喃甲酰肼的反应合成了标题化合物，并通过 IR、（1）H-NMR、元素分析和单晶 X 射线衍射分析（化合物 E2）确证了结构。生物测定结果表明，标题化合物对小菜蛾具有良好的杀虫活性，但杀菌活性较低。令人鼓舞的是，标题化合物对人早幼粒细胞白血病细胞系（HL-60）具有明显的抗癌活性，一些标题化合物对人肝癌细胞系（Bel-7402）、人胃癌细胞系（BGC-823）和人鼻咽癌细胞系（KB）也具有活性。结果表明，先导化合物中的键合对生物活性和光谱很重要。脲键的修饰是发现新农药和药物候选物的有效策略。
