In order to find highly active antidiabetic compounds, fifteen new β-amino ketones containing a isoxazole moiety were synthesized directly through Mannich reaction with facile method and mild reaction condition in the yields of 51.2%～89.3%. Their structures were confirmed by ¹H NMR, ¹³C NMR, ESI MS and HR MS techniques. Preliminary bioassay indicated that although most of these compounds possess weak α-glucosidase inhibitory activity and protein tyrosine phosphatase 1B inhibitory activity in low concentration, some could activate peroxisome proliferator-activated receptors (PPAR) response element moderately. Compound 1-(3,4-dichlorophenyl)-3-(6-methoxynaphthalen-2-yl)-3-(5-methylisoxazol-3-ylamino)propan- 1-one (15) has the strongest activity (75.3%), which deserved further study. The reaction conditions and the structure-activity relationship of these compounds were also discussed in this paper．

Key words: diabetes mellitus, isoxazole, β-amino ketone, Mannich reaction