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.