Design, Synthesis, and Biological Activity of Novel Aromatic Amide Derivatives Containing Sulfide and Sulfone Substructures

In order to explore novel nematicidal and fungicidal lead compounds, two series of target compounds were designed and synthesized by introducing sulfide and sulfone substructures into fluopyram. The bioassays displayed that most compounds showed excellent nematicidal activities at 200 μg/mL in comparison with fluopyram. In terms of fungicidal activity, compound I-9 exhibited almost comparable inhibition rates to that of fluopyram, whose molecular docking simulation indicated the presence of the amide and its ortho-fluorinated groups had an important role on the fungicidal activity. [Display omitted] In recent years, the damage caused by soil nematodes has become increasingly serious; however, the varieties and structures of the nematicides available on the market are deficient. Fluopyram, a succinate dehydrogenase inhibitor (SDHI) fungicide developed by Bayer AG in Germany, has been widely used in the prevention and control of soil nematodes due to its high efficiency and novel mechanism of action. In this paper, two series of novel target compounds were designed and synthesized with nematicidal and fungicidal fluopyram as the molecular skeleton in order to introduce sulfide and sulfone substructures. The structures were identified and characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, and high-resolution mass spectrometer (HRMS). The bioassays revealed that most of the compounds showed excellent nematicidal activities at 200 µg·mL−1 in comparison with fluopyram, while the nematode mortality rate dropped sharply at 100 µg·mL−1, except for compounds I-11 and II-6. In terms of fungicidal activity, compound I-9 was discovered to have an excellent inhibitory rate, and a molecular docking simulation was performed that can provide important guidance for the design and exploration of efficient fungicidal lead compounds.