在新农药创制研究中，生物活性小分子与靶酶之间的选择性相互作用研究是获得高活性先导结构的关键。本项目以农作物真菌CYP51（甾醇14α-去甲基化酶）为靶酶，采用生物合理分子设计法拟设计合成结构新颖的CYP51抑制剂：硝基取代1,3-苯并噁嗪和硝基取代3,1-苯并噁嗪类化合物。通过酶抑制活性及其杀菌活性测定的方法来筛选活性化合物。利用同源模建法、分子对接法、三维定量构效关系分析和实验技术的有机结合来开展活性化合物与靶酶的相互作用机理、构效关系和结构优化的研究，归纳活性化合物与靶酶相互作用规律。经过设计－合成－活性评价－构效关系研究－结构优化的多次循环，力争找到4-6个高活性的新型CYP51抑制剂或具有进一步研究价值的先导化合物。为基于配体－受体相互作用的新农药分子设计提供重要的实验基础和理论依据。

In research and discovery of new pesticides, studies of the selective interaction between biological active molecule and target enzyme is a key to obtain highly active lead compound. On the basis of CYP51 (sterol 14α-demethylase) of the crop fungus, we design novel nitro-1,3-benzoxazines and nitro-3,1-benzoxazines as CYP51 inhibitors by using biorational molecule design method. The synthesis of these compounds will also be investigated. Active compounds will be afforded by evaluation of the inhibitor activity of the mentioned compounds against the CYP51 and their fungicidal activity. Extensive studies on the interaction mechanism between the obtained biological active compound and CYP51, structure-activity relationship and structure optimization of the active compound will be carried out by rational combination of homology modeling, molecular docking, 3D-QSAR and experiment technology, to reveal the interaction law between the active compound and CYP51. 4-6 Novel inhibitors or lead compounds of nitrobenzoxazines with high activity against CYP51 will be possibly obtained through many cycles of design, synthesis, activity assay, structure-activity relationship research and structure optimization. The results of the project will provide important experimental and theoretical basis for molecule design of new pesticides based on the ligand and receptor.