2-氰基苯基磺酰脲衍生物的设计、合成及生物活性研究

Synthesis and Biological Activity of 2-Cyanobenzenesulfonylurea Derivatives

利用药效团拼接和生物电子等排的原理,以氯磺隆和三氟甲磺隆为先导,设计并合成了15个未见文献报道的2-氰基苯基磺酰脲衍生物,通过1H NMR, 13C NMR和HRMS对目标化合物进行结构表征.初步生物活性测试结果表明,部分目标化合物离体抑菌活性和杀虫活性显著.在50 mg·L^(-1)测试剂量下, 5c, 5f和5g对苹果轮纹病菌的抑制率分别为80.3%, 80.3%和83.6%. 5j对东方粘虫在5 mg·L^(-1)测试浓度下的杀虫率可达50%. 5a和5b在0.1 mg·L^(-1)处理浓度下,对尖音库蚊幼虫的杀死率分别为100%和50%,优于对照样氟虫酰胺(20%);当测试浓度为0.01 mg·L^(-1)时, 5a对蚊幼虫仍具有70%的致死率, LC_(50)=0.0023 mg·L^(-1).

In order to study the multi-bioactivity of sulfonylurea derivatives, fifteen novel 2-cyano-6-chlorobenzenesulfonylureas were designed and synthesized according to pharmacophore-combination and bioisosterism strategy, based on the chlorsulfuron and tritosulfuron structure frameworks. Their structures were confirmed by ~1 H NMR, 13 C NMR and HRMS. The preliminary bioactivity test indicated that some of the title compounds had excellent in vitro antibacterial activity and insecticidal activity. For example, at the concentration of 50 mg·L^-1, the antifungal activities of 5 c, 5 f and 5 g against Physalospora piricola were 80.3%, 80.3% and 83.6% respectively. 5 j exhibted 50% larvicidal activity against Mythimna separate Walker at the dosage of 50 mg·L^-1. At the concentration of 0.1 mg·L^-1, 5 a and 5 b showed 100% and 50% insecticidal activity against Culex pipiens pallens, respectively better than that of the control flubendiamide（20%）. At an even low concentration of 0.01 mg·L^-1, 5 a had 70% larvicidal activity, and the LC50 value was 0.0023 mg·L^-1.