超长链脂肪酸延长酶（VLCFAE）抑制剂是一类抗性发展缓慢的除草剂，但存在用药剂量大、对作物安全性低的问题。本项目申请人合成的N-(2,2,2)-三氟乙基吡唑类新化合物除草活性和安全性比商品化VLCFAE抑制剂异丙甲草胺提高6-8倍，是一类未见报道且具有高活性和安全性的VLCFAE抑制剂。为了得到超高活性的VLCFAE抑制剂，本项目拟结合VLCFAE天然底物和商品化VLCFAE抑制剂的化学结构特点，以前期研究发现的N-(2,2,2)-三氟乙基吡唑化合物为先导结构，设计、合成系列三氟乙基吡唑甲基磺酰胺类新化合物，并测定新化合物离体酶抑制活性和活体除草活性；采用比较分子力场分析(CoMFA)方法研究三氟乙基吡唑类化合物空间结构与生物活性之间的定量关系，建立一个预测能力很强的CoMFA模型，依靠模型优化N-(2,2,2)-三氟乙基吡唑类化合物，以期得到超高活性的VLCFAE抑制剂候选除草剂品种。

The inhibitors of very-long-chain fatty acid enlongase (VLCFAE),whose application was limited by the high-dose and low-security, were a type of herbicide with slow resistance development.Previous results showed that the herbicidal activities and selectivity of N-(2,2,2)-trifluoroethylpyrazole derivatives were 6-8 fold better than metolachlor. They could be recognized as potential VLCFAE inhibitors. To obtain herbicidal candidates as the potential VLCFAE inhibitors,this project proposed to synthesize series of novel trifluoroethylpyrazole methylsulfonamide derivatives on basis of lead compound N-(2,2,2)-trifluoroethylprazole derivative according the chemical struture of the VLCFAE natural substrate and VLCFAE inhibitors.The biological activity in vitro and in vivo of these novel compounds were evaluated.Comparative molecular field analysis (CoMFA) was employed to analyze of the three-dimensional quantitative structure activity relationship (3D-QSAR) on series of N-(2,2,2)-trifluoroethylprazole derivatives. The CoMFA model will be used to optimize the derivatives.