Laboratório de Síntese Orgânica Medicinal - LaSOM, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752, Porto Alegre-RS 90610-000, Brazil.
Institute of Chemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, 91501970 RS, Brazil.
Bioorg Med Chem. 2021 Jan 15;30:115934. doi: 10.1016/j.bmc.2020.115934. Epub 2020 Dec 9.
Isoxazoline is a 5-membered heterocycle present in the active compounds of many commercial veterinary anti-ectoparasitic products. The molecular target of isoxazolines is the inhibition of GABA-gated chloride channels in insects. These facts have inspired the use of the isoxazoline scaffold in the design of novel insecticide compounds. The main strategies used for isoxazoline synthesis are either the 1,3-dipolar cycloaddition between a nitrile oxide and an alkene or the reaction between hydroxylamine and an α,β-unsaturated carbonyl compound. This review highlights the utilization of isoxazoline as insecticide: its mode of action, its commercial preparations and its consideration in the design of novel insecticides. Similarity analyses were performed with 235 isoxazoline derivatives in three different cheminformatic approaches - chemical property correlations, similarity network and compound clustering. The cheminformatic methodologies are interesting tools to use in evaluating the similarity between commercial isoxazolines and to clarify the main features explored within their derivatives.
异恶唑啉是 5 元杂环，存在于许多商业兽医抗外寄生虫产品的活性化合物中。异恶唑啉的分子靶标是抑制昆虫的 GABA 门控氯离子通道。这些事实激发了人们使用异恶唑啉支架来设计新型杀虫剂化合物。合成异恶唑啉的主要策略是腈氧化物与烯烃之间的 1,3-偶极环加成反应，或者是羟胺与α,β-不饱和羰基化合物之间的反应。本综述重点介绍了异恶唑啉作为杀虫剂的用途：其作用模式、其商业制剂以及在新型杀虫剂设计中的考虑。利用三种不同的 cheminformatic 方法（化学性质相关性、相似网络和化合物聚类）对 235 种异恶唑啉衍生物进行了相似性分析。化学信息学方法是评估商业异恶唑啉之间相似性和阐明其衍生物中探索的主要特征的有用工具。
