氮杂双环[3.3.1]壬烷芳基噻二唑类化合物合成及其对线虫的抑制活性研究  

Synthesis and Nematicidal Activity of Azabicyclo[3.3.1]nonane-Thiadiazole Derivatives

作　　者：杨天骄 王佳毅[1] 宋恭华[1] YANG Tianjiao;WANG Jiayi;SONG Gonghua(Shanghai Key Laboratory of Chemical Biology,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学药学院上海市化学生物学重点实验室

出　　处：《华东理工大学学报（自然科学版）》2019年第5期750-758,共9页Journal of East China University of Science and Technology

基　　金：国家自然科学基金(21572060)

摘　　要：以具有抗线虫活性的5-HT3受体拮抗剂MDL72222为先导化合物,通过改变氮杂双环中桥环的位置以及桥碳数量,引入农药活性基团噻二唑结构,设计合成了23个未见报道的3-氮杂双环[3.3.1]壬烷芳基噻二唑类化合物。通过核磁共振、高分辨质谱等分析手段确认了化合物的结构。以根结线虫为试虫,测定了目标化合物对根结线虫的生物活性,其中10个目标化合物在质量浓度为40mg/L时对根结线虫表现出一定的抑制活性,在试管实验中化合物Z7对根结线虫表现出较好的抑制活性。Nematodes are crop pests which can cause serious loss in crop production and food crisis.Traditional nematicides,such as Carbamate,isothiocyanate and organophosphates,have largely inhibited the damages of nematodes on agriculture,but they also generate negative effects on both plants and human health,such as root harm and human poisoning.Hence developing novel nematicides with low toxicity and high nematicidal efficiency are extremely urgent.5-HT(5-hydroxytryptamine) is an important monoamine neurotransmitter which plays important role in mammalian endocrine function as well as in the central and peripheral nervous system.5-HT was also found to be an important substance which can control the physiological activities of nematodes including feeding,movement and reproduction.So far,some studies have been reported on the development of 5-HT receptor as potential target for nematicides.Based on the previous achievements performed in our group and the principles of drug development,MDL 72222,a typical 5-HT3 receptor antagonist which can significantly inhibit the swallowing function of the pharyngeal pump in caenorhabditis elegans,has a lethal effect on nematicides at certain doses.Upon changing the configuration or number of carbon atoms of the bridged ring and introducing the bioactive group thiadiazole into the structure of compound MDL 72222,23 new 3-azabicyclo[3.3.1]nonane-thiadiazoles derivatives were designed and synthesized.All the involved compounds were characterized by 1H-NMR,13C-NMR and HRMS.The in vivo bioactivity test was performed using the root-knot nematodes,and the commercial nematocidal agent Avermectin was used as the control product.The nematicidal activity against root-knot nematode was determined.Ten target compounds exhibited certain inhibitory activity against root-knot nematodes at a concentration of 40 mg/L.Notably,compound Z7 showed excellent nematicidal activity in the tube test.

关 键 词：氮杂双环 噻二唑 酰胺 线虫 

分 类 号：O626.423[理学—有机化学]