Design, Synthesis, Biological Evaluation and SARs of Novel N-Substituted Sulfoximfnes as Potential Ryanodine Receptor Modulators

作     者：Yongtao Xie Sha Zhou Yuxin Li Shaa Zhou Minggui Chen Baolei Wang Lixia Xiong Na Yang Zhengming Li 

作者机构：State Key Laboratory of Elemento-Organic Chemistry Department of Chemistry Collaborative innovation Center of Chemical Science and Engineering Nankai University Tianjin 300071 China 

出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)

年 卷 期：2018年第36卷第2期

页      面：129-133页

核心收录：

学科分类：0710[理学-生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070305[理学-高分子化学与物理] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0703[理学-化学] 071002[理学-动物学] 

基　　金：This work was supported by the National Natural Science Foundation of China (31370039  21772103 and 21602118) and the Tianjin Natural Science Foundation (16JCYBJC29400 and 17JCYBJC19900) 

主　　题：sulfoximines SAR insecticidal activity ryanodine receptor 

摘      要：The sulfoximine group has been evaluated as a pharmacophore. Introducing the sulfoximine structure into medicinal compounds as exciting motifs has brought opportunities in drug discovery. In order to develop new ryanodine receptor （RyR） modulators, a series of phthalamides containing sulfoximine derivatives were designed, synthesized, and evaluated against oriental armyworm and diamondback moth for their insecticidal activities. These studies helped to elucidate the electronic and structural requirements around the sulfoximine motif for insecticidal activity. All new structures were synthesized and characterized by ^1H NMR, ^13C NMR, HRMS and bioassay and a preliminary structure-activity relationship （SAR） was discussed. The biological assessment indicated that most title compounds showed good to excellent larvicidal activities. Compounds la, le, and If gave excellent insecticidal activity against oriental armyworm, which showed 100% larvicidal activity at 0.5 mg/L. All compounds showed 100% larvicidal activity at 0.1 mg/L against diamondback moth. In particular, the larvicidal activities of le, If, and lh at 0.0001 mg/L were 50%, 20%, and 40%, respectively, reaching an activity as high as that of the commercial flubendiamide （40%, 0.0001mg/L）. Therefore, Ia, Ie, If and Ih could be considered as new lead structures for the development of new ryanodine receptor （RyR） modulators.