Buysse Ann M, Nugent Benjamin M, Wang Nick X, Benko Zoltan, Breaux Nneka, Rogers Richard, Zhu Yuanming
Dow AgroSciences, Indianapolis, IN, USA.
The University of South Alabama, Mobile, AL, USA.
Pest Manag Sci. 2017 Apr;73(4):731-742. doi: 10.1002/ps.4351. Epub 2016 Sep 7.
The discovery of sulfoxaflor (Isoclast™ active) stemmed from a novel scaffold-based approach toward identifying bioactive molecules. It exhibits broad-spectrum control of many sap-feeding insect pests, including aphids, whiteflies, hoppers and Lygus. Systematic modifications of the substituents flanking each side of the sulfoximine moiety were carried out to determine whether these changes would improve potency.
Structure-activity relationship (SAR) studies showed that, with respect to the methylene linker, both mono- and disubstitution with alkyl groups of varying sizes as well as cyclic analogs exhibited excellent control of cotton aphids. However, against green peach aphids a decrease in activity was observed with substituents larger than ethyl as well as larger cycloalkyl groups. At the terminal tail there appeared to be a narrow steric tolerance as well, with linear groups or small rings more active against green peach aphids than bulkier groups.
A novel series of compounds exploring the substituents flanking the sulfoximine moiety of sulfoxaflor were prepared and tested for bioactivity against cotton aphids and green peach aphids. SAR studies indicated that a decrease in green peach aphid potency was observed at the methylene linker as well as at the terminal tail with bulkier substituents. A quantitative structure-activity relationship analysis of the compounds revealed significant correlation of activity with two molecular descriptors, vol (volume of a molecule) and GCUT_SMR_3 (molar refractivity). This predictive model helps to explain the observed activity with the various substituents. © 2016 Society of Chemical Industry.
氟吡呋喃酮（商品名Isoclast™ active）的发现源于一种基于新型骨架的生物活性分子识别方法。它对多种吸食汁液的害虫具有广谱防治效果，包括蚜虫、粉虱、叶蝉和盲蝽。对砜亚胺部分两侧的取代基进行了系统修饰，以确定这些变化是否会提高药效。
构效关系（SAR）研究表明，对于亚甲基连接基，用不同大小的烷基以及环状类似物进行单取代和双取代均对棉蚜表现出优异的防治效果。然而，对于桃蚜，当取代基大于乙基以及较大的环烷基时，活性会降低。在末端尾部似乎也存在较窄的空间耐受性，直链基团或小环对桃蚜的活性高于体积较大的基团。
制备了一系列新型化合物，探索氟吡呋喃酮砜亚胺部分两侧的取代基，并测试了其对棉蚜和桃蚜的生物活性。SAR研究表明，对于桃蚜，当亚甲基连接基以及末端尾部的取代基体积较大时，活性会降低。对这些化合物的定量构效关系分析表明，活性与两个分子描述符vol（分子体积）和GCUT_SMR_3（摩尔折射率）显著相关。这种预测模型有助于解释观察到的不同取代基的活性。© 2016化学工业协会。
