农药学学报2026，Vol.28Issue(2)：232-244,13.DOI:10.16801/j.issn.1008-7303.2026.0025
新型噁二唑烟酰胺类4-羟苯基丙酮酸双加氧酶抑制剂的设计、合成及生物活性
Design and biological activity of novel oxadiazole nicotinamide derivatives as 4-hydroxyphenylpyruvate dioxygenase inhibitors
摘要
Abstract
The high herbicidal efficacy and low risk of resistance of 4-hydroxyphenylpyruvate dioxygenase(HPPD)inhibitors have made them an important focus in herbicide discovery.In this study,based on an active substructure splicing strategy,a series of 21 novel 2-trifluoromethyl oxadiazole nicotinamide derivatives(6,7a-7t)were designed and synthesized.Their structures were fully characterized by 1H NMR,13C NMR,and high-resolution mass spectrometry(HRMS).Enzyme inhibition assays against AtHPPD revealed that several compounds,including 7a(IC50=0.362 μmol/L),7s(IC50=0.221 μmol/L),and 7t(IC50=0.117 μmol/L),exhibited inhibitory activities comparable to or better than the commercial herbicide mesotrione(IC50=0.363 μmol/L).Further molecular docking simulations were conducted to rationalize the observed differences in inhibitory activity.Greenhouse herbicidal assays demonstrated that most compounds showed inhibitory effects against the tested weeds.Among them,the methylsulfonyl-substituted compound 7h and the ethylurea-substituted compound 7n exhibited the most promising herbicidal efficacy.At an application rate of 150 g a.i./hm2,both compounds provided over 80%control against Echinochloa crus-galli,Setaria viridis,Digitaria sanguinalis,Amaranthus retroflexus,Chenopodium album,and Abutilon theophrasti,with particularly superior activity against Setaria viridis compared to mesotrione.Meanwhile,compounds 7h and 7n displayed good crop safety toward maize,wheat,and foxtail millet.These results suggest that the oxadiazole nicotinamide scaffold represents a promising lead structure for herbicide development,and compounds 7h and 7n may serve as potential candidates for the development of next-generation HPPD-inhibiting herbicides.关键词
4-羟苯基丙酮酸双加氧酶/噁二唑烟酰胺/除草活性/作物安全性/分子设计Key words
4-hydroxyphenylpyruvate dioxygenase/oxadiazole nicotinamide/herbicidal activity/crop safety/molecular designe分类
化学化工引用本文复制引用
谢丁涛,王梦寒,陈利军,姚建威,王大伟..新型噁二唑烟酰胺类4-羟苯基丙酮酸双加氧酶抑制剂的设计、合成及生物活性[J].农药学学报,2026,28(2):232-244,13.基金项目
国家重点研发计划(No.2021YFD1700100). Supported by State Key Research and Development Program of China(No.2021YFD1700100). （No.2021YFD1700100）
