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.