肉桂酰天冬氨酸类氨肽酶N抑制剂的合成和初步活性研究  

Synthesis and preliminary activity assay in vitro of cinnamoyl asparagines derivatives as aminopeptidase N(APN/CD13) inhibitors

作　　者：刘英姿[1,2] 杨康辉[1] 徐文方[1] 

机构地区：[1]山东大学药学院,山东济南250012 [2]山东警察学院刑事技术系,山东济南250014

出　　处：《中国药物化学杂志》2009年第4期241-246,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家高技术研究发展计划项目(863项目;2007AA02Z314);国家自然科学基金项目(90713041)

摘　　要：目的以氨肽酶N（APN／CD13）为药物作用靶点，设计合成一系列新型的肉桂酰天冬氨酸类衍生物，并对其进行抑制活性评价。方法以肉桂酸和L-天冬氨酸甲酯为基本原料经缩合、水解、酸化、环合反应得到关键中间体环状酸酐，再经氨解反应合成了一系列新型的肉桂酰天冬氨酸类衍生物；采用体外抑酶试验测定化合物对氨肽酶N的抑制活性。结果与结论合成了24个未见文献报道的肉桂酰天冬氨酸类衍生物，其结构经过。H-NMR、MS谱确证。其中化合物6d、6g、6k、6l显示出较好的抑制氨肽酶N活性（IC50=12—28μmol·L^-1），有进一步研究的价值。Aim To discovery novel aminopeptidase N inhibitors as anticancer agents, a new series of cinnamoyl asparagine derivatives were designed and synthesized. Methods The target compounds were synthe- sized through condensation, hydrolyzation and acidification, followed by cyclization in acetic anhydride then aminolysis. Their inhibitory activities against the enzyme were evaluated in vitro. Results and conclusion Twenty-four novel cinnamoyl asparagines derivatives were synthesized and their structures were comfirmed by ^1H-NMR,ESI-MS. Four compounds （6d, 6g, 6k and 61） show better potent activities （ IC50 = 12 - 28 μmol. L ^-1 ） against aminopeptidase N, which are worthy of further investigation as lead antitumor compounds.

关 键 词：肉桂酰天冬氨酸 氨肽酶N抑制剂 抗肿瘤 

分 类 号：R914[医药卫生—药物化学]