Abstract: 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-azabicyclo3.3.1nonane-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.