Xiong Li, Li Hua, Jiang Li-Na, Ge Jing-Ming, Yang Wen-Chao, Zhu Xiao Lei, Yang Guang-Fu
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, People's Republic of China.
Collaborative Innovation Center of Chemical Science and Engineering , Tianjin 300071, People's Republic of China.
J Agric Food Chem. 2017 Feb 8;65(5):1021-1029. doi: 10.1021/acs.jafc.6b05134. Epub 2017 Jan 31.
A series of diphenyl ether-containing pyrazole-carboxamide derivatives was designed and synthesized as new succinate ubiquinone oxidoreductase (SQR) inhibitors. This highly potent molecular scaffold was developed from a moderately activie hit 3, obtained from our previous pharmacophore-linked fragment virtual screening (PFVS) method. The results of greenhouse tests indicated that some analogues showed good SQR inhibitory activity, with promising fungicidal activity against Rhizoctonia solani and Sphaerotheca fuliginea at a dosage of 200 mg/L. Most surprisingly, compound 62 showed the highest SQR inhibitory activity with a K value of 0.081 μM, about 4-fold more potent than penthiopyrad (K = 0.307 μM). In addition, compounds 43 and 62 displayed excellent fungicidal activity even at a dosage as low as 6.25 mg/L, which was superior to thifluzamide. Moreover, compound 62 exhibited excellent protection effect against R. solani and provided about 81.2% protective control efficancy after 21 days with two sprayings. The present work indicated that these two compounds could be used as potential agricultural fungicides targeting SQR.
设计并合成了一系列含二苯醚的吡唑 - 甲酰胺衍生物作为新型琥珀酸泛醌氧化还原酶（SQR）抑制剂。这种高效的分子骨架是由我们之前通过药效团连接片段虚拟筛选（PFVS）方法得到的中等活性命中物3开发而来的。温室试验结果表明，一些类似物表现出良好的SQR抑制活性，在200 mg/L的剂量下对立枯丝核菌和黄瓜白粉菌具有良好的杀菌活性。最令人惊讶的是，化合物62表现出最高的SQR抑制活性，K值为0.081 μM，比戊唑吡菌胺（K = 0.307 μM）的活性高约4倍。此外，化合物43和62即使在低至6.25 mg/L的剂量下也表现出优异的杀菌活性，优于噻氟酰胺。此外，化合物62对立枯丝核菌表现出优异的保护作用，两次喷雾后21天提供约81.2%的保护防治效果。目前的工作表明，这两种化合物可作为针对SQR的潜在农用杀菌剂。
