Design and Synthesis of Novel N-(Pyrazol-4-yl)benzamide Derivatives Featuring a Diphenylamine or Diphenyl Ether Scaffold as Potential Broad-Spectrum SDH Inhibitors.

A series of novel N-(pyrazol-4-yl)benzamide derivatives featuring diphenylamine or diphenyl ether scaffolds was synthesized and evaluated for antifungal activities. Remarkably, compound 6i demonstrated potent broad-spectrum efficacy against five fungal species, particularly Sclerotinia sclerotiorum, with a half maximal effective concentration (EC50) value of 0.44 μg/mL, outperforming Boscalid (EC50 = 0.71 μg/mL) and nearing Fluxapyroxad (EC50 = 0.26 μg/mL). Additionally, compound 6i exhibited substantial protective effects against S. sclerotiorum on oilseed rape leaves, Rhizoctonia solani on rice leaves, and Valsa mali on apple fruits at 100 μg/mL. Scanning electron microscopy (SEM) analysis further confirmed that 6i could inflict significant damage to S. sclerotiorum hyphae. Further succinate dehydrogenase (SDH) enzymatic inhibition assays, molecular docking, and molecular dynamics (MD) simulations indicated that compound 6i could potentially act as a succinate dehydrogenase inhibitor (SDHI). These findings suggested that 6i held significant promise as an innovative broad-spectrum SDHI for crop protection, warranting further investigation.