Design, Synthesis And Antifungal Activity Of Novel Pyrazolopyrimidinone Derivatives

Succinate dehydrogenase(SDH)has been shown to be one of the most effective targets for fungicides,and Succinate dehydrogenase inhibitors(SDHIs)all have a distinctly common feature,containing a core backbone amide bond.In this paper,pyrazole carboxamide was used as the main core skeleton,and a candidate compound library of polycyclic heterocyclic small molecules containing about 500 pyrazole amide skeletons was established by using fragment-based drug design and pharmacophore strategy.Based on the results of the screening,three small peptides containing pyrazolecarboxamide were designed and synthesized.30 novel derivatives containing pyrazolopyrimidine heterocycles were synthesized from these 3 intermediates with 10 different nicotinic acids.Then the structure and configuration of the compounds were determined by 1H NMR,13C NMR and MS.The antifungal activity of the target compounds against 6 different fungi was tested,and the preliminary design of pesticide molecules was preliminarily verified rationality.As one of the most classical skeletons of succinate dehydrogenase,the amide was used as the core skeleton.Three intermediates containing pyrazole carboxamide derivatives were synthesized and designed,and 30 pyrazolopyrimidinone derivatives were synthesized and evaluated for antifungal activity by introducing active nicotinic acid.The results showed that the activity of the target compound of the substituent on the benzene ring was changed,5-(2-chloroethyl)-1-(4-chloropheny l)-6-(2-fluoropyridin-3-yl)-1,5-dihy dro-4H-pyrazolo[3,4-d]pyrimidin-4-one,which has an EC50 value of 2.92 mg/L and 4.78 mg/L for Valsa mali andPhysalospora piricola,The results provide a valuable reference for the development of pyrazolopyrimidinone derivatives as potential succinate dehydrogenase inhibitors.