新型N-[2-((取代苯基)氨基)吡啶-3-基]嘧啶甲酰胺的合成、杀菌活性及分子对接

Synthesis,Fungicidal Activity and Molecular Docking Study of Novel N-[2-((Substitutedphenyl)amino)pyridin-3-yl]-pyrimidine-4-carboxamides

为寻找新型结构的琥珀酸脱氢酶抑制剂,以高效杀菌剂啶酰菌胺为先导化合物,设计、合成了17种N-[2-((取代苯基)氨基)吡啶-3-基]-4-甲基-2-甲硫基嘧啶-5-甲酰胺(4a^4g)和N-[2-((取代苯基)氨基)吡啶-3-基]-4-甲氧基-2-甲硫基嘧啶-5-甲酰胺(4h^4q),并通过1 H NMR、13C NMR和MALDI-TOF-MS确证了化合物的结构.离体杀菌活性试验表明,在剂量为50μg/mL时,16种化合物对菌核菌表现出较高的杀菌活性,抑制率在90%以上.一些化合物在此剂量下对灰霉菌显示出中等活性,抑制率为70%~84%.分子对接研究揭示了具有较高活性的化合物,N-[2-((3-氟-4-甲基苯基)氨基)吡啶-3-基]-2-甲硫基-4-甲氧基嘧啶-5-甲酰胺(4p)与琥珀酸脱氢酶(SDH)靶酶氨基酸形成4个氢键和一个阳离子-π相互作用.

To explore succinate dehydrogenase inhibitor with new structure,the excellent fungicide boscalid was chosen as a lead compound,and seventeen N-[2-((substitutedphenyl)amino)pyridin-3-yl]-4-methyl-2-(methylthio)pyrimidine-5-carboxamides(4a^4g)and N-[2-((substitutedphenyl)amino)pyridin-3-yl]-4-methoxy-2-(methylthio)pyrimidine-5-carboxamides(4h^4q)were designed and synthesized.The structures of target compounds were characterized by 1 H NMR,13C NMR,and MALDI-TOF-MS.The in vitro bioassay showed that sixteen compounds possessed high fungicidal activity against S.sclerotiorum with more than 90%inhibitory rate at 50μg/mL,and some compounds showed moderate activity against B.cinerea at the same dose with inhibitory rate in the range of 70%~84%.The molecular docking study revealed that four hydrogen bonds and one cation-πinteraction were formed between N-[2-((3-fluoro-4-methylphenyl)amino)pyridin-3-yl]-4-methoxy-2-(methylthio)pyrimidine-5-carboxamide(4p)and succinate dehydrogenase(SDH)enzyme.