L-异谷氨酰胺类氨肽酶N抑制剂的合成及初步活性

目的 设计并合成一系列新型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，与3，4-二氯苯甲酸形成酰氯发生酰化、环合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，其结构经过¹H-NMR、MS、和IR的确证。其中化合物I₄、I₆显示出较好的抑制氨肽酶N活性(IC₅₀=20~40 μmol.L^-1)，有进一步研究的价值。

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

Aim To design and synthesize new L-iso-glutamine derivatives and to evaluate their Aminopeptidase N inhibitory activities in vitro. Methods The target compounds were synthesized starting from the acylation reaction of 3,4-dichlorobenzoic acid with L-glutamic acid to form the basic scaffold, followed by the cyclic reaction in acetic anhydride and ammoniac decomposing reaction, 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 by¹H-NMR spectra, MS and IR. Compound I₄ and I₆ exhibit potent aminopeptidase N inhibitory activities (IC₅₀=20-40 μmol.L^-1) and are worthy of further investigation．