大环内酯抗生素是治疗细菌感染的重要药物。阿奇霉素和克拉霉素作为第二代大环内酯类，比红霉素具有更好的药代动力学性质和稳定性。然而，越来越严重的细菌耐药性问题促使研发新型大环内酯的需求十分迫切 。本项目设计、合成了三个系列以ermB编码的甲基化的核糖体为靶点的2´位修饰的脱克拉定糖阿奇霉素衍生物并测试其体内外抗菌活性.在此基础上，进行构效关系分析和作用机制研究。同时，采用细胞计数、显微镜观察、定量实时PCR等手段，通过分析阿奇霉素衍生物对PA感染的小鼠的TLR4表达及相关炎症因子的影响来研究抗炎活性，目的是得到具有多种药理作用的氮杂内酯类化合物。前期已完成部分化合物的合成和测活工作，结果表明它们对erm甲基化耐药性肺炎链球菌、mef外排泵耐药菌、双重耐药菌都表现出了显著活性，后期将通过作用机制研究和抗炎活性测试，有望为大环内酯抗生素提供具有抗耐药菌活性和抗炎活性的新型先导。

The macrolide antibiotics are the most important drug for the treatment of bacterial infections. Azithromcin and clarithromycin are great examples of the second generation macrolides, which have better pharmacokinetic profiles and are more stable than erythromycin. However, the increasing drug resistance makes it an urgent need to discover novel macrolide antibotics. Targeting ermB-mediating dimethylated ribosome, three series of 2´-modified descladinosylazithromycin derivatives are designed, synthesized and evaluated for their antibacterial actitiy in vitro and vivo. Based on this, we will summarize their SAR and study the mechanism. In addition, we analyze the effect of the compounds on TLR4 expression and relative inflammatory factors in mouse model of PA pulmonary infection by cell counting, fluorescence microscope observation and quantitative real time PCR to evaluate their inflammatory activity. The goal is to find azilides with multiple and pharmacological functions. We have sythesized several derivatives, they exhibited excellent activity against ermB resistant S. pneumoniae, mefA resistant S. pneumonia and ermB + mefA resistant S. pneumoniae. The mechanism research and anti-inflammatory activity evaluation will be completed later. In the future, novel agents with a antiinflammatory effect and antibacterial activity will be created.