Design, synthesis, nematicidal activity, and preliminary mechanism of pyrimidine derivatives through the scaffold hopping strategy

BACKGROUND: Plant-parasitic nematodes pose a severe threat to crops, causing over $175 billion in economic losses to global agriculture. RESULTS: ) values of 3.7 mg/L and 11.4 mg/L against Meloidogyne incognita and Aphelenchoides besseyi, respectively, significantly superior to the lead nematicide tioxazafen. Compound D27 exhibited excellent in vivo nematocidal activity against M. incognita in tomatoes (93.3%) at 50 mg/L, which was significantly superior to the positive control tioxazafen (45.3%). Compound D27 not only induced significant oxidative stress adverse reactions in nematodes, but also decreased the frequency of head swinging and inhibited their egg-hatching capacity. In addition, compound D3 significantly inhibits the feeding and reproductive capacity of Bursaphelenchus xylophilus, affects the activity of defense enzymes (superoxide dismutase, peroxidase, and catalase) within the organism, and inhibits the activity of the succinate dehydrogenase enzyme. CONCLUSION: This scaffold can serve as the core structure for discovery of novel nematicides. We continue to optimize this scaffold structure, aiming to discover highly effective novel nematicides in future research. © 2026 Society of Chemical Industry.