BACKGROUNDSuccinate dehydrogenase inhibitor (SDHI) fungicides have been widely utilized in the combat of plant pathogenic fungi due to their potent, broad‐spectrum antifungal activity and unique mode of action. In this study, a series of novel 4‐sulfur‐substituted pyrazol‐5‐yl‐benzamide derivatives containing amide, hydrazide, or ester moieties were synthesized to develop innovative SDH inhibitors.RESULTSThe bioassay studies indicated that several compounds exhibited potent in vitro fungicidal activity against various fungi. Particularly, compound 4d demonstrated broad‐spectrum fungicidal efficacy, with EC50 values of 0.21, 0.95, 0.64, 1.33, and 0.66 mg L−1 against Valsa mali, Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum, and Gaeumannomyces graminis, respectively. In vivo studies demonstrated that compound 4d effectively prevented V. mali infection in apples at 50 mg L−1, showing superior protective and curative effects (93.4% and 85.5%) compared to lead compound A27 (68.7% and 57.0%) and commercial fungicide fluxapyroxad (55.4% and 43.6%). Enzymatic inhibition assays and molecular docking analysis suggested that compound 4d could serve as a potential SDH inhibitor.CONCLUSIONThis study offers valuable insights for expanding the fungicidal spectrum of pyrazol‐5‐yl‐benzamide derivatives and further developing them as novel SDH inhibitors. © 2025 Society of Chemical Industry.

中文翻译：

---

发现新型 4-硫取代的吡唑-5-基-苯甲酰胺衍生物，其中含有酰胺/酰肼/酯部分作为潜在的琥珀酸脱氢酶抑制剂

背景蔗糖脱氢酶抑制剂 （SDHI） 杀菌剂因其强大的广谱抗真菌活性和独特的作用方式而被广泛用于对抗植物病原真菌。在这项研究中，合成了一系列含有酰胺、酰肼或酯部分的新型 4-硫取代的吡唑-5-基-苯甲酰胺衍生物，以开发创新的 SDH 抑制剂。结果生物测定研究表明，几种化合物对各种真菌表现出强大的体外杀菌活性。特别是，化合物 4d 显示出广谱杀菌功效，对 Valsa mali、Botrytis cinerea、Rhizoctonia solani、Fusarium graminearum 和 Gaeumannomyces graminis 的 EC50 值分别为 0.21、0.95、0.64、1.33 和 0.66 mg L-1。体内研究表明，化合物 4d 在 50 mg L-1 时有效预防苹果中的马里弧菌感染，与铅化合物 A27（68.7% 和 57.0%）和商业杀菌剂氟虫唑（55.4% 和 43.6%）相比，显示出卓越的保护和治疗效果（93.4% 和 85.5%）。酶抑制测定和分子对接分析表明，化合物 4d 可以作为潜在的 SDH 抑制剂。结论本研究为扩大吡唑-5-基-苯甲酰胺衍生物的杀菌谱并进一步将其开发为新型 SDH 抑制剂提供了有价值的见解。© 2025 化工学会.