Pyridazine Derivatives as Insecticides: Synthesis, Insecticidal Activity, Molecular Docking, and Density Functional Theory Studies of Some New 2-Substituted Methyl-3-oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonitriles

Abstract The rapid emergence of insecticide resistance among agricultural pests underscores the urgent need for new bioactive chemical frameworks. Pyridazines have emerged as an attractive core structure for the innovation of next-generation agrochemicals. In this study, we synthesized and structurally characterized a series of novel 2-substituted methyl-3-oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonitriles 4a, 4b, 6a, 6b, 8a–g, and 10–14. All new compounds were tested for their insecticidal activity against the cowpea aphid, Aphis craccivora. Moreover, molecular docking simulations, molecular dynamics simulations, density functional theory calculations, and other theoretical studies of some representative compounds were included. The bioassay results demonstrated that the new derivatives exhibited considerable insecticidal efficacy, with compound 13 showing activity comparable to that of the commercial reference acetamiprid. The robust concordance between experimental and computational results validates the designed analogues as promising candidates for sustainable crop protection and establishes a rational design paradigm for next-generation nAChR-targeting pesticides with enhanced efficacy and improved safety profiles.