Design, Synthesis, and Pesticidal Activities of Pyrimidin-4-amine Derivatives Bearing a 5-(Trifluoromethyl)-1,2,4-oxadiazole Moiety

Abstract

It is important to discover new pesticides with new modes of action because of the increasing evolution of pesticide resistance. In this study, a series of novel pyrimidin-4-amine derivatives containing a 5-(trifluoromethyl)-1,2,4-oxadiazole moiety were designed and synthesized. Their structures were confirmed by 1 H NMR, 13 C NMR, and HRMS. Bioassays indicated that the 29 compounds synthesized possessed excellent insecticidal activity against Mythimna separata, Aphis medicagini, and Tetranychus cinnabarinus and fungicidal activity against Pseudoperonospora cubensis. Among these pyrimidin-4-amine compounds, 5-chloro-N-(2fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl)pyrimidin-4-amine (U7) and 5-bromo-N-(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl) pyrimidin-4-amine(U8) had broad-spectrum insecticidal and fungicidal activity. The LC 50 values were 3.57 ± 0.42, 4.22 ± 0.47, and 3.14 ± 0.73 mg/L for U7, U8, and flufenerim against M. separata, respectively. The EC 50 values were 24.94 ± 2.13, 30.79 ± 2.21, and 3.18 ± 0.21 mg/L for U7, U8, and azoxystrobin against P. cubensis, respectively. The AChE enzymatic activity testing revealed that the enzyme activities of compounds U7, U8, and flufenerim are 0.215, 0.184, and 0.184 U/mg prot, respectively. The molecular docking results of compounds U7, U8, and flufenerim with the AChE model demonstrated the opposite docking mode between compound U7 or U8 and positive control flufenerim in the active site of AChE. The structure−activity relationships are also discussed. This work provided excellent pesticide for further optimization. Density functional theory analysis can potentially be used to design more active compounds.

Design, synthesis, and fungicidal activity of novel N‐substituted piperazine‐containing phenylpyridines against cucumber downy mildew

“…According to the frontier molecular orbital theory, the LUMO accepts electrons, whereas the HOMO donates electrons. HOMO and LUMO are the most critical factors that affect the bioactivity 40,41 . From Table 4 and Fig.…”

“…HOMO and LUMO are the most critical factors that affect the bioactivity. 40,41 From Table 4 and Fig. 4, the structure of compound C8 contains three parts: the phenylpyridine ring, piperazine ring and 4-t-Bu phenyl ring.…”

Novel Pyrimidine Derivatives Bearing a 1,3,4-Thiadiazole Skeleton: Design, Synthesis, and Antifungal Activity

“…Meanwhile, in the agricultural field, pyrimidine derivatives also have good biological activities such as antiviral ( Wu, et al, 2015 ; Zan et al, 2020 ), insecticidal ( Liu, et al, 2017 ; Wu, et al, 2019 ; Chen, et al, 2021 ; Liu, et al, 2021 ; Sun, et al, 2021 ), fungicidal ( Guan et al, 2017 ; Yan et al, 2020 ; Yang, et al, 2020 ), bactericidal ( Li et al, 2020 ), herbicidal ( Chen et al, 2019 ; Li et al, 2020 ), and anticancer ( Guo et al, 2020 ) properties. In the last few decades, some pyrimidine derivatives have been commercialized as pesticides for controlling plant diseases and insect pests.…”

Isolation, Synthesis, and Fungicidal Activity of Isopropyl (3-methyl-1-oxo-1-((1-((4-(prop-2-yn-1-yloxy)phenyl)thio)propan-2-yl)amino)butan-2-yl)carbamate Diastereomers against Phytophthora capsici

“…In recent years, modern agriculture, including economic crops, flowers, fruits, trees, and vegetables, were affected by insects, weeds, and diseases. e effective tools to protect plants are pesticides [1][2][3][4][5], which have been an important work in modern agriculture. Phytophthora capsici is an important pathogenic fungal with a wide host range, which is very harmful and destructive to host plants, and often leads to serious losses in crop production.…”