中文摘要：

目的寻找具有较高APN酶抑制活性的新型化合物。方法以光学纯的L-谷氨酰胺为原料,经Boc保护、环合、取代、脱Boc保护、缩合、催化氢化、缩合、脱Boc保护成盐等反应合成目标化合物。并对目标化合物进行了初步的体外抑酶活性试验。结果合成了1个未见文献报道的N-取代-2,6-哌啶二酮类氨肽酶N（APN/CD13）抑制剂：（R）-2-氨基-N-（（S）-1-（2-（2-（二甲胺基）乙氨基）-2-氧乙基）-2,6-二氧哌啶-3-基）-3-苯丙酰胺,其结构经核磁共振氢谱和电喷雾质谱确证。结论目标化合物对APN表现出一定的抑制活性,其IC50值为56.4μmol.L-1,但低于阳性对照药Bestatin（IC50值为3.6μmol.L-1）。通过进一步的结构修饰,有望找到活性更好的化合物。

英文摘要：

Aminopeptidase N（APN/CD13） is an important zinc dependent metallo-exopeptidase,which is over expressed in tumor cells and plays a critical role in tumor invasion,metastasis and tumor angiogenesis.In order to find better aminopeptidase N inhibitors,One N-substituted-2,6-dioxopiperidin derivative（S）-2-amino-N-（（S）-1-（2-（2-（dimethylamino）ethylamino）-2-oxoethyl）-2,6-dioxopiperidin-3-yl）-3-phenylpropanamide（8） was synthesized.Boc-L-glutamine（2） was synthesized from optical pure L-glutamine by protection with（Boc）2O and then cyclization in the presence of DCC and NHSu in THF.（S）-tert-butyl-2,6-dioxopiperidin-3-ylcarbamate（3）,which was synthesized by alkylation of compound 2 with benzyl bromoacetate,was then treated with TFA to give compound 4.Then compound 4 was coupled with Boc-L-Phe to give compound 5,which was then catalytically hydrogenated using 10% Pd/C to afford compound 6.Coupling between compound 6 and N,N-dimethylpropan-1-amine in the presence of CDI gave compound 7.Compound 7 was finally treacted with HCl-EtOAc to give the target compound 8.The in vitro inhibitory activity of the target compound against APN was evaluated,and the IC50 value was 56.4 μmol · L-1（the IC50 value of the control Bestatin was 3.6 μmol · L-1）.The result showed that the target compound had some activity while it need further modification to find better APN inhibitors.