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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1H-NMR、MS谱确证。其中化合物6d、6g、6k、6 l显示出较好的抑制氨肽酶N活性(IC50=12~28μm ol.L-1),有进一步研究的价值。
OBJECTIVE To design and synthesize a series of novel cinnamoyl aspartate derivatives by using aminopeptidase N (APN / CD13) as drug targets and to evaluate its inhibitory activity. Methods Cinnamic acid and L-aspartic acid methyl ester as the basic raw materials by condensation, hydrolysis, acidification, cyclization reaction to obtain the key intermediate cyclic anhydride, and then aminolysis reaction was synthesized a series of new cinnamoyl aspartate Acid derivatives; Compounds were tested for their inhibitory activity on aminopeptidase N using in vitro protease assays. RESULTS AND CONCLUSION Twenty four cinnamoyl aspartate derivatives were synthesized and their structures were confirmed by 1H-NMR and MS spectra. Compounds 6d, 6g, 6k, 6 l showed better inhibition of aminopeptidase N activity (IC50 = 12 ~ 28μm ol.L-1), which has further research value.