Design, Synthesis, and Fungicidal Activity of Pyrimidinamine Derivatives as Novel Complex I Inhibitors

To develop novel fungicides targeting complex I, a series of pyrimidinamine derivatives bearing a dichloropropene ether moiety were designed and synthesized via the intermediate derivatization method. Their structures were confirmed by 1 H/ 13 C NMR, elemental analysis, HRMS, and single-crystal X-ray diffraction. Bioassays showed that several compounds exhibited excellent activity against wheat powdery mildew. Notably, compound 3 (EC 50 = 0.440 mg/L) was significantly more potent than propiconazole (EC 50 = 5.99 mg/L) and diflumetorim (EC 50 = 4.12 mg/L). Structure–activity relationships were analyzed and further supported by molecular docking. DFT calculations indicated higher reactivity and stronger protein-binding ability for compound 3, consistent with its bioactivity. Transcriptome analysis of Blumeria graminis revealed differentially expressed genes (DEGs) enriched in pathways related to complex I, suggesting it as the potential target. Overall, compound 3 could be a promising agrochemical fungicide candidate for further development.