多取代吡啶酮衍生物的设计、合成及对DPP-Ⅳ蛋白酶的抑制活性研究

Design, Synthesis and Inhibitory Activities of Multi-substituted Pyridone Derivatives on DPP-IV Protease

摘要:

通过分析alogliptin与DPP-Ⅳ蛋白酶的构效关系，通过骨架跃迁以及官能团互换，设计并合成出15个多取代吡啶酮类化合物，通过 1H NMR和Ms确定了它们的结构，并对其进行了初步的体外酶活性筛选, 得到了3个化合物11a、38、41与alogliptin活性相当的化合物，初步确立了此类化合物的DPP-Ⅳ酶构效关系。

Abstract:

By analyzing the structure-activity relationship of alogliptin with DPP-Ⅳ, We used the strategy of skeleton transition and functional groups swap to design and synthesize 15 multi-substituted pyridone compounds. And we determined their structures of all compounds by 1H NMR and ESI-Mass and got three compounds 11a, 38, 41 which had quite activity with alogliptin through preliminary activity screening in vitro, initially identified the structure-activity relationships of these compounds with DPP-Ⅳ.