趋化因子受体表达异常是导致多种疾病发生的重要原因之一，参与细胞生长信号转导的趋化因子受体2（CXCR2）已成为一个重要的抗癌药物作用靶点。在前期研究中，首先通过同源蛋白模型建立，然后依据CXCR2 活性部位特点，利用组合库设计及虚拟筛选发现了一类多环噁二唑结构的新颖CXCR2拮抗剂，能有效抑制肿瘤细胞HGC-27 与A549 的生长，并明显的具有选择性抑制CXCR2的能力。本项目拟在此基础上，用基于片段的分子设计方法和类药性早期评价，对先导化合物JKM-28进行结构优化，建立多环噁二唑类似结构母核的合成方法学.设计合成基于多环噁二唑基结构的系列衍生物，并进行生物活性评价。以期获得结构新颖、高活性、低毒的CXCR2拮抗剂。

The abnormal expression of chemokine receptor is one of the important causes of many diseases. The chemokine receptor 2 (CXCR2), which is involved in cell growth signaling, has become an important target for anticancer drug action. In previous studies, first by homologous protein model, then according to CXCR2 activity characteristics of the parts, we found a novel polycyclic oxadiazole CXCR2 antagonist which can effectively inhibit the growth of tumor cells HGC-27 and A549, and obviously with selective inhibition of CXCR2 ability by using of combinatorial library design and virtual screening. Based on the previous study, lead compounds JKM-28 will be optimized using fragment-based molecular design method and drug-like evaluation, as well as the similar heterocyclic compounds synthesis methods will be developed. Finally,design and synthesis a series of derivatives based on the polycyclic oxadiazole structure. The biological activity of these compounds will be subsequently evaluated.Hopefully we will find high activity and low toxicity CXCR2 antagonists.