中文摘要：

目的设计并合成凋亡抑制蛋白（IAPs）小分子抑制剂。方法基于对Smac和Caspase-9分别与XIAP—BIR3结合位点的分析，辅以分子对接实验，设计并合成两类结构的化合物；采用荧光极化各向异性（FPA）竞争试验法测定合成的目标化合物对XIAP和cIAP1的抑制活性。结果合成两类结构共16个新类肽化合物，其结构经MS和^1H-NMR谱确证；荧光极化各向异性（FPA）竞争试验结果显示，噻唑烷环衍生物Ⅱ对XIAP—BIR3和cIAP1-BIR3具有显著的抑制活性，其中，化合物Ⅱf抑制XIAP—BIR3和cIAP—BIR3的IC50值分别为0．29、0．055μmol·L^-1。结论发现了新的IAPs抑制剂，并得出初步构效关系，为进一步的结构优化奠定了基础。

英文摘要：

Aim To find small molecule inhibitors of inhibitor apoptosis proteins （LAPs）. Methods Combining with Dock method and basing on the structure of active site of XIAP-BIR3 binding to Smac and Caspase-9, two series target compounds were designed and synthesized. Fluorescence polarization anisotropy （FPA） competitive test were used to evaluate the inhibitory activity of these target compounds against XIAP-BIR3 and cIAP1-BIR3. Results Sixteen peptidomimeptics were synthesized and their structures were identified by MS and ^1H-NMR. Binding assay（FPA） showed that the thiazolidine derivatives Ⅱ had obvious inhibitory activity against XIAP and cIAP1. Especially, the IC50 values of compound Ⅱ f against XIAP-BIR3 and cIAP1-BIR3 were 0. 29 and 0. 055 μmol· L^-1 respectively. Conclusion New LAPs inhibitors were discovered. The preliminary structure-activity relationship concluding from this research will give a foundation for the further structural optimization of these IAPs inhibitors.