L-异谷氨酰胺类氨肽酶N抑制剂的合成及初步活性  

Synthesis and preliminary activity assay in vitro of L-iso-glutamine derivatives as aminopeptidase N(APN) inhibitors

作　　者：杨康辉[1] 廖一静[2] 麦曦[2] 徐文方[1] 

机构地区：[1]山东大学药学院,山东济南250012 [2]南昌大学医学院药学系,江西南昌330006

出　　处：《中国药物化学杂志》2009年第1期15-19,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家高技术研究发展计划项目(2007AA02Z314)

摘　　要：目的设计合成一系列新型L-异谷氨酰胺类衍生物,并测定其对氨肽酶N(APN)的抑制活性。方法以L-谷氨酸为基本骨架,经与3,4-二氯苯甲酸反应得到关键中间体环状酸酐,再经氨解反应合成目标化合物。采用体外抑酶试验测定化合物抑制氨肽酶N的活性。结果与结论合成了15个未见报道的L-异谷氨酰胺衍生物,其结构经1H-NMR、MS、和IR谱确证。其中化合物Ⅱ4、Ⅱ6显示出较好的抑制氨肽酶N的活性(IC50=20～40μmol.L-1),有进一步研究的价值。Aim To design and synthesize new L-iso-glutarnine derivatives and to evaluate their aminopeptid- ase N inhibitory activities in vitro. Methods The target compounds were synthesized starting from the acylation of 3,4-dichlorobenzoic acid with L-glutamic acid to form the basic scaffold,followed by the cyclization in acetic anhydride and ammonolysis, and their aminopeptidase N inhibitory activities are assayed in vitro. Results and conclusion Fifteen novel L-iso-glutamine derivatives were synthesized, and their structures were confirmed by 1H-NMR spectra, MS and IR. Compound Ⅱ 4 and Ⅱ 6 exhibit potent aminopeptidase N inhibitory activities（ IC50 = 20 - 40 umol· L^ - 1 ） and are worthy of further investigation.

关 键 词：L-异谷氨酰胺衍生物 氨肽酶N 抑制剂 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]