Structure-based bioisosterism design, synthesis, insecticidal activity and structure–activity relationship (SAR) of anthranilic diamide analogues containing 1,2,4-oxadiazole rings

BACKGROUND: Anthranilic diamide derivatives are among the most important classes of synthetic insecticides. Moreover, the 1,2,4-oxadiazole heterocycle, a bioisostere of amide, has been extensively used in pesticides. In order to discover novel molecules with high insecticidal activities, a series of anthranilic diamide analogues containing 1,2,4-oxadiazole rings were designed and synthesised. RESULTS: A series of novel anthranilic diamide derivatives containing 1,2,4-oxadiazole were obtained, and confirmed by ¹H and ¹³C nuclear magnetic resonance and high-resolution mass spectrometry. The structure of 3-bromo-N-(4-chloro-2-methyl-6-{3-[(methylsulphonyl)methyl]-1,2,4-oxadiazol-5-yl}phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide was further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed 100% mortality against Plutella xylostella at 100 mg L⁻¹, and compound 3IIl showed 90% larvicidal activities at a concentration of 0.5 mg L⁻¹. The LC₅₀ value of 3IIl was 0.20 mg L⁻¹, which indicated that it may be used as a potential leading compound for further structural optimisation. Furthermore, brief comparative molecular field analysis (CoMFA) models were established to study the structure–activity relationships (SARs) of the title compounds. CONCLUSION: Compound 3IIl may be used as a potential leading compound for further structural optimisation, and SARs and CoMFA models could provide reliable clues for further structural optimisation.