Succinate dehydrogenase inhibitors (SDHIs) have become one of the most important classes of agrochemical fungicides. According to the data from FRAC, the resistance risk for SDHIs had reached up to medium and even to high. In general, the chemical structure of SDHIs mainly contained three fragments: an acid core, a hydrophobic tail, and an amide linker, corresponding to three modification directions for each fragment. Among them, amide linker modification (ALM) has become a research hotspot for the design of novel SDHIs fungicides in recent years. We presented here a detailed review on the ALM strategy in the past decade, and some of them had entered the market. According to their chemical structures, ALM strategy were classified into four parts: (1) linked aliphatic chain between amide bond and hydrophobic tail, (2) introducing substituents to replacing hydrogen atom in the amide bond, (3) reverse extending the amide linker, and (4) changed with other bioisosteres. Moreover, the structure–activity relationship and the interaction mechanism of ALM-SDHI with SDH were discussed. This review aims to provide a global perspective on research and development of novel SDHIs, as well as suggestions for food safety management.

中文翻译：

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琥珀酸脱氢酶抑制剂中酰胺接头修饰的全面概述


琥珀酸脱氢酶抑制剂 （SDHIs） 已成为最重要的农用化学品杀菌剂类别之一。根据 FRAC 的数据，SDHIs 的耐药风险已达到中等甚至高。一般来说，SDHIs的化学结构主要包含三个片段：酸核、疏水尾和酰胺接头，对应每个片段的三个修饰方向。其中，酰胺接头修饰 （ALM） 已成为近年来新型 SDHIs 杀菌剂设计的研究热点。我们在这里详细回顾了过去十年的 ALM 策略，其中一些已经进入市场。根据它们的化学结构，ALM 策略分为四个部分：（1） 酰胺键和疏水尾部之间的连接脂肪链，（2） 在酰胺键中引入取代基以取代氢原子，（3） 反向延伸酰胺接头，以及 （4） 与其他生物等排体改变。此外，讨论了 ALM-SDHI 与 SDH 的结构-活性关系和相互作用机制。本文旨在为新型 SDHIs 的研究和开发提供全球视角，并为食品安全管理提供建议。