Design, , Synthesis and Fungicidal Activity of Pyrazinamide Analogs

Pyraziflumid was a novel pyrazinamide analog fungicide developed by Nihon Nohyaku Co. In this work, 16 pyrazinamide analogs were synthesized using substituted pyrazine acid and 2-methyl-3-nitrophenol as initial materials through 4 steps. The structures of the target compounds were confirmed by nuclear magnetic resonance (1H NMR, 13C NMR) and high resolution mass spectrometer(HRMS). The results of fungicidal activity at greenhouse showed that pyrazinamide analogs had excellent fungicidal activities against corn rust at 6.25 mg/L. Among them, the fungicidal activities of compounds 4, 5, 7, 8, 15 and 16 against corn rust at 6.25 mg/L were 100%. Molecular docking simulations revealed that compound 16 interacted with TRP-173 of succinate dehydrogenase(SDH) through hydrogen bonding, which could explain the probable mechanism of action between compound 16 and the target protein. These results indicated that compound 16 might be a promising fungicide candidate and provide valuable reference for further investigation.