中文摘要：

目的 设计合成一系列2-氰基-3,12-二氧代齐墩果烷-1,9（11）-二烯-28-酰胺类化合物,以期寻找活性更好的抗肿瘤化合物。方法 以2-氰基-3,12-二氧代齐墩果烷-1,9（11）-二烯-28-羧酸（CDDO）为先导化合物,将CDDO的17位羧基通过连接基团与各种氨基化合物进行偶联制得目标化合物;采用MTT法测试偶联物对乳腺癌MDA-MB-468细胞的增殖抑制活性。结果与结论 目标化合物的结构经IR、MS及1H-NMR谱确证,合成的10个化合物对乳腺癌MDA-MB-468细胞显示出不同程度的增殖抑制活性,明显优于先导化合物CDDO,其中,化合物2i、2j的活性最强（IC50值分别为1.12、1.37μmol·L^-1）。构效关系研究发现,二胺偶联物的活性最好,氨基酸和正丙醇胺偶联物的活性次之,而芳胺偶联物的活性较弱,化合物2i和2j值得进一步研究。

英文摘要：

Oleanolic acid （OA） derivatives 2-cyano-3,12-dioxooleana-1,9 （ 11 ） -dien-28-oic acid （ CDDO ）, its ester（CDDO-Me） ,amide（CDDO-Im） ,and lactone olean-28,13fl-olide are stronger than OA to suppress inflammation, activate cytoprotective pathways, inhibit proliferation, and induce apoptosis of cancer cells. In- deed, CDDO-Me has been tested in the phase I clinical trial for the treatment of advanced solid tumors and lymphoid malignancies. To continue our development of novel synthetic triterpenoids with improved antican- cer activity, ten new CDDO-amide derivatives were designed and synthesized starting from CDDO. Their structures were confirmed by IR, MS and ^1H-NMR. The antiproliferative effects of the target compounds on MDA-MB-468 cells were evaluated by MTT assays. The majority of these derivatives showed stronger anti- proliferative activity than the lead compound CDDO. Among them, compounds 2i and 2j displayed the most potent inhibitory activity（ IC5o = 1.12 μmol·L^-1 and 1.37μmol·L^-1 respectively）, which may be potential chemotherapeutic agents for further investigation. The preliminary structure-activity relationships reveal that the introduction of amino acid and polyamine moiety to 17-COOH of CDDO is beneficial to enhance the an- tiproliferative activity.