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

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

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1HNMR和质谱确定了它们的结构,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,初步确立了该类化合物的DPP-Ⅳ酶构效关系。

By analyzing the structure-activity relationship of alogliptin with DPP-IV, the strategy of skeleton transition and functional groups swap was used to design and synthesize 15 multi-substituted pyridone compounds. And the structures of all the compounds were determined by 1^HNMR and ESI- Mass and three compounds 11a,38,41 which had quite similar activity to that of alogliptin were selected through preliminary activity screening in vitro, and the structure-activity relationships of these compounds with DPP-IVwere tentatively identified.