N‐Methoxy Pyrazole‐4‐Carboxamide Derivatives: Synthesis, Spectral Analyses, Antifungal Activity, In Silico Molecular Docking, ADMET, and DFT Studies

Abstract

Succinate dehydrogenase inhibitor (SDHI) is an important fungicide to control grain diseases. For this reason, a series of novel pyrazole‐4‐carboxamide derivatives with an N‐methoxy group were designed and synthesized. All the target compounds were characterized by 1H NMR, 13C NMR, and HRMS. The compound 3c was further confirmed by X‐ray diffraction, which crystallized in the triclinic system, space group P‐1, Z = 2. The fungicidal activity results indicated that most of these compounds possessed good activity against Sclerotinia sclerotiorum at 50 ppm. Especially, compound 3h exhibited the best activity with the EC50 is 7.80 μg/mL, which is comparable with the positive control bixafen (EC50 = 6.70 μg/mL). Furthermore, the physicochemical properties, molecular docking simulation, ADMET analyses, DFT of compounds 3h, 3k and two commercial SDHIs, isoflucypram and pydiflumetofen, were investigated in this study.