摘要/Abstract

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¹H 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50 μg/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.
关键词: 嘧啶, 酰胺, 合成, 杀菌活性, 分子对接
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-carbox-amides (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 ¹H 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 50 μg/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-π interaction were formed between N-[2-((3-fluoro-4-methylphenyl)amino)pyridin-3-yl]-4-methoxy-2-(methyl-thio)pyrimidine-5-carboxamide (4p) and succinate dehydrogenase (SDH) enzyme.
Key words: pyrimidine, carboxamide, synthesis, fungicidal activity, molecular docking


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