程敬丽, 李安邦, 肖豆鑫, 赵金浩. N-取代苯基-4-(1-甲基-1H-吡唑-5-基)噻吩-2-甲酰胺的合成、杀菌活性及分子对接[J]. 农药学学报, 2021, 23(5): 877-885. DOI: 10.16801/j.issn.1008-7303.2021.0096
    引用本文: 程敬丽, 李安邦, 肖豆鑫, 赵金浩. N-取代苯基-4-(1-甲基-1H-吡唑-5-基)噻吩-2-甲酰胺的合成、杀菌活性及分子对接[J]. 农药学学报, 2021, 23(5): 877-885. DOI: 10.16801/j.issn.1008-7303.2021.0096
    CHENG Jingli, LI Anbang, XIAO Douxin, ZHAO Jinhao. Synthesis, fungicidal activity and molecular docking of N-substitutedphenyl-4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide[J]. Chinese Journal of Pesticide Science, 2021, 23(5): 877-885. DOI: 10.16801/j.issn.1008-7303.2021.0096
    Citation: CHENG Jingli, LI Anbang, XIAO Douxin, ZHAO Jinhao. Synthesis, fungicidal activity and molecular docking of N-substitutedphenyl-4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide[J]. Chinese Journal of Pesticide Science, 2021, 23(5): 877-885. DOI: 10.16801/j.issn.1008-7303.2021.0096

    N-取代苯基-4-(1-甲基-1H-吡唑-5-基)噻吩-2-甲酰胺的合成、杀菌活性及分子对接

    Synthesis, fungicidal activity and molecular docking of N-substitutedphenyl-4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxamide

    • 摘要: 为了寻找结构新颖的琥珀酸脱氢酶 (SDH) 类衍生物,在前期发现吡唑联苯甲酰胺基础上,采用骨架跃迁的策略,设计并合成了18个N-取代苯基-4-(1-甲基-1H-吡唑-5-基) 噻吩-2-甲酰胺类衍生物 ( 3a~3n4a ~ 4d ),其中17个为新化合物。通过 1H NMR、13C NMR 和高分辨质谱 (HRMS) 确证了化合物的结构。离体杀菌活性测试结果表明:部分化合物对小麦赤霉病菌Fusarium graminearum、马铃薯早疫病菌Alternaria solani和草莓灰霉病菌 Botrytis cinerea 显示出较好的杀菌活性,其中化合物 3k4d 对小麦赤霉病菌的EC50值分别为18.5和14.3 mg/L,化合物 4d 对马铃薯早疫病菌的EC50值为15.7 mg/L,活性略高于对照药剂噻呋酰胺 (EC50值27.8 mg/L),化合物 3k3m 对草莓灰霉病菌的EC50值分别为15.3和 9.9 mg/L,与噻呋酰胺活性 (EC50值10.4 mg/L) 相当。分子对接研究结果显示:具有较高活性的化合物N-(4-氟苯基乙基)-4-(1-甲基-1H-吡唑-5-基) 噻吩-2-甲酰胺 ( 3m ) 与靶酶 (SDH) 的氨基酸残基之间存在较强的氢键作用。

       

      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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