Synthesis and Biological Activities of Novel Pyrazole Carboxamides Containing an Aryloxypyridyl Ethylamine Module

Pyrazole carboxamide is widely utilized in agricultural crop protection. In this research, we synthesized two classes of compounds, namely, pyrazole-5-carboxamide (4a) and pyrazole-4-carboxamide (4b), which are distinguished by the inclusion of the N-1-(6-aryloxypyridin-3-yl) ethylamine skeleton. This design was inspired by the frequent occurrence of diaryl ether modules in pesticide molecules. The bioassay results revealed that some compounds 4a exhibit higher insecticidal activity (IA) than 4b, while some compounds 4b display stronger fungicidal activity compared to 4a. This suggests that pyrazolyl plays a crucial role in determining the selectivity of these compounds toward different biological species. Notably, compound 4a-14 not only retains the potent activity of tolfenpyrad, the exact lead compound of 4a, against Lepidoptera pest Plutella xylostella and Thysanoptera pest Frankliniella occidentalis but also shows excellent IA against pests with piercing-sucking mouthparts, such as Aphis craccivora Koch and Nilaparvata lugens. This research has important implications for the control of pests with piercing-sucking mouthparts and the development of new insecticides and fungicides. The findings highlight the potential of inhibitory complex I as an effective control target for these pests, particularly those that have developed resistance to traditional insecticides. Additionally, it sheds light on the binding mode of 4b-11 and complex II, which serves as a negative reference for the design of SDHI fungicides. The study emphasizes the significance of pyrazolyl in determining selectivity in biological species and identifies avenues for future research in enhancing the biological activity of amino modules. The discovery of (S)-4a-14 not only presents a promising candidate compound for pesticide development but also provides valuable insights into the inhibitory effect of a respiratory chain complex on piercing-sucking insect pests. These findings have important implications in both theory and practice, offering new directions for pest control strategies and pesticide and fungicide development.

fungicidal activity; insecticidal activity; plug-in molecules; pyrazole carboxamide.