Richoux Gary M, Yang Liu, Norris Edmund J, Tsikolia Maia, Jiang Shiyao, Linthicum Kenneth J, Bloomquist Jeffrey R
Emerging Pathogens Institute, Entomology and Nematology Department, University of Florida, Gainesville, Florida 32610 United States.
Center for Medical, Agricultural and Veterinary Entomology, Agricultural Research Service (ARS), United States Department of Agriculture (USDA), Gainesville, Florida 32608 United States.
J Agric Food Chem. 2020 Nov 25;68(47):13960-13969. doi: 10.1021/acs.jafc.0c03333. Epub 2020 Nov 4.
A total of 115 aryl amides were synthesized and screened for vapor repellency against the Orlando (OR) strain of mosquitoes. Of these compounds, 29 had 1 h repellency EC values comparable to or better than ,-diethyl--toluamide (DEET, 1 h EC value of 35 μg/cm), with 2,2,3,3,3-pentafluoro--(4-fluorophenyl)propenamide () and 2,2,3,3,4,4,4-heptafluoro--(3,4,5-trifluorophenyl)butanamide () exhibiting the most potent EC values of 4.5 and 2.9 μg/cm, respectively. The cross-resistance of select, highly potent, derivatives against the pyrethroid-resistant Puerto Rico (PR) strain of was also investigated, and little to no resistance was observed. When synergized with 1--permethrinic acid (TFA), compound had a 1 h EC value 6 times lower than metofluthrin against OR and 40 times lower against PR mosquitoes. Additionally, preliminary mammalian oral toxicity was screened for compounds and , and both exhibited LD values of >2000 mg/kg. The structure-activity relationship analysis, which guided the synthesis of these derivatives, is given, and key trends are highlighted to inform future analogue design.
总共合成了115种芳基酰胺，并针对奥兰多（OR）品系蚊子的驱避性进行了筛选。在这些化合物中，有29种的1小时驱避EC值与N，N-二乙基甲苯酰胺（避蚊胺，1小时EC值为35μg/cm²）相当或更好，其中2,2,3,3,3-五氟-N-（4-氟苯基）丙烯酰胺（化合物1）和2,2,3,3,4,4,4-七氟-N-（3,4,5-三氟苯基）丁酰胺（化合物2）表现出最强的EC值，分别为4.5和2.9μg/cm²。还研究了选定的高效衍生物对拟除虫菊酯抗性波多黎各（PR）品系蚊子的交叉抗性，几乎未观察到抗性。当与1-苯氧基菊酯酸（TFA）协同作用时，化合物1对OR品系蚊子的1小时EC值比甲氧氟氯菊酯低6倍，对PR品系蚊子低40倍。此外，对化合物1和2进行了初步的哺乳动物口服毒性筛选，两者的LD₅₀值均>2000mg/kg。给出了指导这些衍生物合成的构效关系分析，并突出了关键趋势，以为未来的类似物设计提供参考。
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