慢性阻塞性肺病(chronic obstructive pulmonary disease，COPD)是一种以气流受限为特征，包含了多种疾病状态的肺部炎性疾病，具有较高的发病率和死亡率。研究发现，趋化因子受体CXCR2拮抗剂具有良好的COPD治疗效果。然而这类药物分子的结构种类有限、不同系列化合物之间的结构差异小，拮抗活性在纳摩尔级的化合物寥寥无几，仅仅局限于少数几个处于临床试验的药物分子。本项目拟在临床II期CXCR2小分子拮抗剂的结构基础上，利用环化策略对药物分子的构象进行限制，通过对活性构象的分析，寻找并发现具有活性构象的新颖结构，同时辅助其他设计手段，如电子等排、药效团整合等，并综合考虑氢键供体/受体的数目、cLogP等理化性质参数对化合物进行合理的优化、结构改造，旨在获得全新结构的活性更高、成药性更佳的CXCR2拮抗剂用于COPD的治疗。

Chronic obstructive pulmonary disease (COPD), characterized by a limited airflow, is a serious pulmonary inflammatory disease with high morbidity and mortality including multiple disease states. Recent research found that Chemokine receptor CXCR2 antagonists have good effect of COPD treatment. However, some limitations are not ignored. For example, the structural skeletons are limited; structural differences are not significant; only a small number of drug molecules in clinical trials have potent activity at nanomolar lever. In this application project, systematical study on the design and synthesis of CXCR2 antagonists based on a clinical compound is proposed. The cyclization strategy is used to limit the conformation of drug moleculers, in order to find and discover a novel structure via reasonable analysis of active conformation. In addition, assisted by other design methods, such as electronic isometric principle, pharmacophores integration, et al, designed compounds are optimized according to their physical and chemical properties including number of hydrogen bond donor/acceptor, cLogP and so on, in order to get a new structure CXCR2 antagonist with higher activity and better drug effect for COPD treatment.