Based on the modification of natural products and the active substructure splicing method, a series of new N-(thiophen-2-yl) nicotinamide derivatives were designed and synthesized by splicing the nitrogen-containing heterocycle natural molecule nicotinic acid and the sulfur-containing heterocycle thiophene. The structures of the target compounds were identified through 1H NMR, 13C NMR and HRMS spectra. The in vivo bioassay results of all the compounds against cucumber downy mildew (CDM, Pseudoperonospora cubensis (Berk.et Curt.) Rostov.) in a greenhouse indicated that compounds 4a (EC50 = 4.69 mg/L) and 4f (EC50 = 1.96 mg/L) exhibited excellent fungicidal activities which were higher than both diflumetorim (EC50 = 21.44 mg/L) and flumorph (EC50 = 7.55 mg/L). The bioassay results of the field trial against CDM demonstrated that the 10% EC formulation of compound 4f displayed excellent efficacies (70% and 79% control efficacies, respectively, each at 100 mg/L and 200 mg/L) which were superior to those of the two commercial fungicides flumorph (56% control efficacy at 200 mg/L) and mancozeb (76% control efficacy at 1000 mg/L). N-(thiophen-2-yl) nicotinamide derivatives are significant lead compounds that can be used for further structural optimization, and compound 4f is also a promising fungicide candidate against CDM that can be used for further development.

中文翻译：

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N-(噻吩-2-基)烟酰胺衍生物的设计、合成及杀菌活性。

基于天然产物的修饰和活性亚结构拼接方法，将含氮杂环天然分子烟酸和含硫杂环拼接设计合成了一系列新型N-(噻吩-2-基)烟酰胺衍生物噻吩。目标化合物的结构通过1H NMR、13C NMR和HRMS谱进行了鉴定。所有化合物在温室中对黄瓜霜霉病（CDM，Pseudoperonospora cubensis (Berk.et Curt.) Rostov.）的体内生物测定结果表明，化合物 4a (EC50 = 4.69 mg/L) 和 4f (EC50 = 1.96 mg /L) 表现出优异的杀菌活性，高于双氟草胺 (EC50 = 21.44 mg/L) 和氟吗啉 (EC50 = 7.55 mg/L)。针对 CDM 的田间试验的生物测定结果表明，化合物 4f 的 10% EC 制剂显示出优异的功效（分别为 70% 和 79% 的控制效果，分别为 100 mg/L 和 200 mg/L），优于那些两种商业杀真菌剂 flumorph（200 mg/L 时控制效果为 56%）和代森锰锌（1000 mg/L 时控制效果为 76%）。N-(thiophen-2-yl) 烟酰胺衍生物是重要的先导化合物，可用于进一步的结构优化，化合物 4f 也是一种有前途的 CDM 杀菌剂候选物，可用于进一步开发。分别为 100 mg/L 和 200 mg/L），优于两种商业杀菌剂氟吗啉（200 mg/L 时 56% 的防治效果）和代森锰锌（1000 mg/L 时 76% 的防治效果）。N-(thiophen-2-yl) 烟酰胺衍生物是重要的先导化合物，可用于进一步的结构优化，化合物 4f 也是一种有前途的 CDM 杀菌剂候选物，可用于进一步开发。分别为 100 mg/L 和 200 mg/L），优于两种商业杀菌剂氟吗啉（200 mg/L 时 56% 的防治效果）和代森锰锌（1000 mg/L 时 76% 的防治效果）。N-(thiophen-2-yl) 烟酰胺衍生物是重要的先导化合物，可用于进一步的结构优化，化合物 4f 也是一种有前途的 CDM 杀菌剂候选物，可用于进一步开发。