氮桥杂环新烟碱杀虫剂的设计合成与生物活性研究

作用于烟碱型乙酰胆碱受体的新烟碱类杀虫剂研究是国际上农药创制的热点领域之一。由于新烟碱化合物的频繁使用，抗性问题日益严重，蜂毒问题逐渐突出。基于靶标设计合成结构新颖、作用机制独特的新先导具有重要的研究价值和潜在的应用前景。.本项目以烟碱型乙酰胆碱受体为靶标，从氧桥杂环新烟碱杀虫剂环氧虫啶结构出发，设计合成含氮的桥杂环系列化合物，测试化合物对各种害虫的生物活性，详细考察氮原子和桥杂环上取代基、桥杂环的尺寸对活性及nAChRs的拮抗作用的影响，构建QSAR方程，总结烟碱乙酰胆碱受体拮抗剂具备的结构特征。利用拮抗剂GYM与AChBP的复合物晶体结构和桥杂环化合物的结构，以AChBP为受体蛋白进行分子对接，尝试初步建立氧（氮）桥杂环拮抗剂的作用模型。本项目旨在发现高活性先导化合物，为解决农业害虫的抗性防治问题寻找新的途径，对于新农药创制和农业重要害虫防治具有重要意义。

Neonicotinoids acting on the nicotinic acetylcholine receptors (nAChRs) are one of the hot-spots in the field of new pesticides innovation of global. The resistance problem is becoming more serious and the toxicity of honeybee is being accentuated because neonicotinoics are used frequently. To design and synthesis leading compounds with new structures and novel mode of action is very important for the research and has potential application prospects..This project designs and synthesizes series of azabridged neonicotinoids based on the structure of oxabridged neonicotinoid cycloxaprid and using nAChRs as target. The bioactivites against various insects are measured. The influence of the subsitutes on nitrogen atom and on bridged ring and the size of bridge ring to the bioactivities and antagonistic effect will be investigated. Then, the equations of QSAR are estabilished and the structure characters of nAChRs antagonist are generalized. The binding mode is tried to investigated through docking between the structures of oxa(aza)bridged ring compounds and AChBP based on the crystal structure of nAChRs antagonist GYM/AChBP complex. The target of this project is to find high activities leading compounds and to solve the resistance problem of agriculture crop protection, which is significant for the research of new pesticides and pest management.