Synthesis, fungicidal activity and molecular docking of N-substitutedphenyl-4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide
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Abstract
In order to find novel succinate dehydrogenase inhibitors, based on the previous discovery of the pyrazole-benzoic scaffold, the scaffold hopping strategy was used to design and synthesize 18 N-substitutedphenyl-4-(1-methyl)-1H-pyrazol-5-yl)thiophene-2-carboxamide derivatives ( 3a - 3n , 4a - 4d ), of which 17 are new compounds. Their structures were confirmed by 1H NMR, 13C NMR and HRMS . The fungicidal activity test in vitro showed that some compounds had good activity against Fusarium graminearum, Alternaria solani and Botrytis cinerea. Among them, the EC50 values of compound 3k and 4d against F. graminearum were 18.5 mg/L and 14.3 mg/L, respectively. The EC50 value of compound 4d against A. solani was 15.7 mg/L. It was higher than 27.8 mg/L of thiafluzamide. The EC50 value of compound 3k and 3m against B. cinerea were 15.3 mg/L and 9.9 mg/L, which was equivalent to that of the control agent thiafluzamide (EC50 10.4 mg/L). The molecular docking study revealed that strong hydrogen bond was formed between the compound N-(4-fluorophenylethyl)-4-(1-methyl-1H-pyrazol-5-yl) thiophene-2-carboxamide ( 3m ) and succinate dehydrogenase (SDH).
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