Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
CreInSol Consulting & Biocontrols, CH-4118 Rodersdorf, Switzerland.
J Agric Food Chem. 2022 Sep 14;70(36):11042-11055. doi: 10.1021/acs.jafc.2c00785. Epub 2022 May 12.
The application of agrochemicals is critical to global food safety. Nowadays, environmentally friendly green agrochemicals are the trend in field crop protection. The research and development of nematicides absorbed more attention as a typical representation of agrochemicals. This review describes the origin of recently commercialized nematicides, the application of bioisosterism and scaffold hopping in the discovery and optimization of agrochemicals, especially nematicides, and novel bioisosteric design strategies for the identification of fluensulfone analogues. Pesticide repurposing, high-throughput screening, computer-aided drug design, and incorporation of known pharmacophoric fragments have been the most successful approach for the discovery of new nematicides. As outlined, the strategies of bioisosteric replacements and scaffold hopping have been very successful approaches in the search for new nematicides for sustainable crop protection. In the exploration of novel fluensulfone analogues with nematicidal activity, bioisosteric replacement of sulfone by amide, chain extension by insertion of a methylene group, and reversal of the amide group have proven to be successful approaches and yielded new and highly active fluensulfone analogues. These attempts might result in compounds with an optimal balance of steric, hydrophobic, electronic, and hydrogen-bonding properties and contribute to deal with the complex problem during the research and development of new nematicides. Further ideas are also put forward to provide new approaches for the molecular design of nematicides.
农用化学品的应用对全球食品安全至关重要。如今，环保型绿色农用化学品是田间作物保护的趋势。杀线虫剂的研究与开发作为农用化学品的典型代表，受到了更多的关注。本综述描述了最近商品化的杀线虫剂的起源，生物等排体和骨架跃迁在农用化学品，特别是杀线虫剂的发现和优化中的应用，以及鉴定 fluensulfone 类似物的新型生物等排设计策略。农药再利用、高通量筛选、计算机辅助药物设计以及已知药效团片段的引入已成为发现新杀线虫剂的最成功方法。如前所述，生物等排替换和骨架跃迁策略在寻找可持续作物保护的新杀线虫剂方面是非常成功的方法。在探索具有杀线虫活性的新型 fluensulfone 类似物时，通过酰胺替代砜、通过插入亚甲基进行链延长以及酰胺基团的反转已被证明是成功的方法，并产生了新的、高活性的 fluensulfone 类似物。这些尝试可能会产生具有最佳空间、疏水性、电子和氢键性质平衡的化合物，并有助于解决新杀线虫剂研发过程中的复杂问题。还提出了进一步的想法，为杀线虫剂的分子设计提供新的方法。
