Synthesis and aphicidal activity of insect kinin analogs modified with pyridine

To discover novel aphicidal compounds and provide more effective pest management solutions for agricultural production, the highly active insect kinin mimic Ⅳ-3, previously discovered by our research group, was selected as a lead compound. A total of 12 novel target analogs were designed by replacing the styrene moiety of the cinnamoyl group at the N-terminus with a pyridine ring fragment through active substructure stitching while maintaining the tetrapeptide structure, and prepared using the Fmoc solid-phase synthesis method. Their structures were confirmed by HRMS and ¹H NMR. The bioassay results showed that all the target compounds had aphicidal activity against A. glycines. The activity of Ⅱ-10 (LC₅₀ = 4.5 µmol/L) was superior to that of the lead compound Ⅳ-3 (LC₅₀ = 16.63 µmol/L) and the commercially available pymetrozine (LC₅₀ = 19.75 µmol/L). Preliminary structure-activity relationship analysis suggested that aphicidal efficacy is influenced by both the position and the type of substituents on the pyridine ring, with the 4-position substitution and CF₃ substituent proving most effective. This study provides valuable insights for the development of novel insect kinin-based aphicides.