With the advancement of artificial intelligence technology in protein structure modeling, predicting the structure of RyRs from its sequence has become an effective approach for developing insecticides. Building on this application of AI in insecticide development, a series of novel polysubstituted pyridine compounds containing a unique 5-(furan-2-yl)-1H-pyrazole-3-carboxamido scaffold were designed and synthesized. These compounds were characterized using 1H NMR, 13C NMR, 19F NMR spectroscopy and HRMS. Subsequently, their insecticidal activities were evaluated. The results of these bioassays indicated that certain compounds exhibited promising activities against Mythimna separate and Plutella xylostella. Notably, compound I-6 displayed 47% insecticidal activity at a concentration of 0.01 μg/mL, which reached the same activity level as the control Chlorantraniliprole, while compound I-26 demonstrated 50% larvicidal activity against M. separata at 10 μg/mL. Furthermore, the toxicity of I-26 (IC50 0.007365 μg/mL) was superior to that of chlorantraniliprole (CHL) (IC50 1.059 μg/mL), suggesting that it could serve as a lead compound for further optimization. Molecular docking was employed to predict the binding positions of the compounds, which showed a good correlation between their insecticidal activities and their binding values. This study provided a template for future AI applications in RyR pesticide development.