Design, Synthesis, and Biological Activity of Novel Diazabicyclo Derivatives as Safeners.

Herbicide safeners selectively protect crops from herbicide damage without reducing the herbicidal efficiency on target weed species. The title compounds were designed by the intermediate derivatization approach and fragment splicing to exploit novel potential safeners. A total of 31 novel diazabicyclo derivatives were synthesized by the microwave-assistant method using isoxazole-4-carbonyl chloride and diazabicyclo derivatives. All synthetic compounds were confirmed by infrared, ¹ H and ¹³ C nuclear magnetic resonance, and high-resolution mass spectrometry. The bioassay results demonstrated that most of the title compounds could reduce the nicosulfuron phytotoxicity on maize. The glutathione S -transferase (GST) activity in vivo was assayed, and compound 4 ( S15 ) revealed an inspiring safener activity comparable to commercialized safeners isoxadifen-ethyl and BAS-145138. The molecular docking model exhibited that the competition at the active sites of target enzymes between compound 4 ( S15 ) and nicosulfuron was investigated with respect to herbicide detoxification. The current work not only provided a powerful supplement to the intermediate derivatization approach and fragment splicing in design pesticide bioactive molecules but also assisted safener development and optimization.