新机制新靶点新型抗炎药物的研究具有重大的意义。课题组前期通过系统合成筛选获得了多个具有明确抗炎活性的4-取代-苯并噁唑酮衍生物，初步研究提示该类活性化合物可能是通过调控炎症重要因子TNF-α与IL-1介导的信号通路来发挥抗炎作用的，但具体机制和作用靶点尚不清楚。为此，拟以前期获得的具有显著抗炎活性的化合物4-邻甲基苯磺酰氧基苯并噁唑酮（MBB）为先导化合物，合成构建新型苯并噁唑酮小分子库，以获得具有更高抗炎活性的新结构化合物，以其作为小分子探针，综合应用分子生物学技术研究其调控炎症重要因子TNF-α与IL-1介导的信号通路的具体途径，进一步运用蛋白质组学技术系统的探讨其抗炎机制；通过分析差异蛋白，并结合计算机辅助设计软件与细胞热转变分析技术，寻找作用靶点。本研究结果将为该类化合物进一步结构优化提供科学依据，也为新机制新靶点抗炎药物的设计提供理论依据。

The research on new anti-inflammatory drugs with new mechanism of action and new target is of great significance. A series of 4-substituted benzoxazolone derivatives with determined anti-inflammatory activity was synthesized in our research group. The preliminary study presented that the regulation of TNF-αand IL-1 mediated signaling pathways might be the crucial anti-inflammatory mechanism of these compounds, but the specific pathways and target were unclear. Therefore, a new series of benzoxazolone derivatives will be synthesized on the basis of the lead compound 4-o-methyl-benzenesulfonyl benzoxazolone (MBB) to gain high anti-inflammatory agent as the small-molecule probe. Then, the inflammatory factors TNF-a and IL-1 mediated inflammatory mechanism will be discussed to elaborate whether these signal pathways played important roles in the anti-inflammatory activity of these compounds. Afterwards, the proteomic technology is used to illuminate the activity mechanism systematacially. Finally, the target of the compounds will be discussed using cell thermal analysis technology combined with the analyzing of the altered proteins and computer aided design software. The results will provide scientific basis for the further structural optimization of this kind of compounds, and provide new thoughts for the design of novel anti-inflammatory drugs with new mechanism and target.