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Thirty-one uracil-based derivatives were synthesized and preliminary screening by measuring glucose consumption in HepG2 cells,expression of adiponectin and leptin in 3T3-L1 adipocytes.Compound 8g showed the most potential activity and then chosen to be evaluated in HFD-Induced male Wistar rats.Compound 8g induced significant weight loss and regulated the serum levels of biochemical markers compared to metformin.8g could also improve glucose tolerance as determined by oral glucose tolerance test(OGTT) and intravenous glucose tolerance test(IGTT).