Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety

To accelerate the development of novel fungicides, a variety of N-(pyrazol-5-yl)benzamide derivatives with a diphenylamine moiety were designed and synthesized using a pharmacophore recombination strategy based on the structure of pyrazol-5-yl-aminophenyl-benzamides. The bioassay results demonstrated that most of the target compounds had excellent in vitroantifungal activities against Sclerotinia sclerotiorum, Valsa mali, and Botrytis cinerea. In particular, compound 5IIIhexhibited remarkable activity against S. sclerotiorum(EC50= 0.37 mg/L), which was similar to that of fluxapyroxad (EC50= 0.27 mg/L). In addition, compound 5IIIc(EC50= 1.32 mg/L) was observed to be more effective against V. malithan fluxapyroxad (EC50= 12.8 mg/L) and comparable to trifloxystrobin (EC50= 1.62 mg/L). Furthermore, compound 5IIIhdemonstrated remarkable in vivoprotective antifungal properties against S. sclerotiorum, with an inhibition rate of 96.8% at 100 mg/L, which was close to that of fluxapyroxad (99.6%). Compounds 5IIIc(66.7%) and 5IIIh(62.9%) exhibited good in vivoantifungal effects against V. maliat 100 mg/L, which were superior to that of fluxapyroxad (11.1%) but lower than that of trifloxystrobin (88.9%). The succinate dehydrogenase (SDH) enzymatic inhibition assay was conducted to confirm the mechanism of action. Molecular docking analysis further revealed that compound 5IIIhhas significant hydrogen-bonding, π–π, and p−π conjugation interactions with ARG 43, SER 39, TRP 173, and TYR 58 in the binding site of SDH, and the binding mode was similar to that of the commercial fungicide fluxapyroxad. All of the results suggest that compound 5IIIhcould be a potential SDH inhibitor, offering a valuable reference for future studies.