2-O-Carboxymethylpyrogallol derivatives as PTP1B inhibitors with antihyperglycemic activity

2-O-Carboxymethylpyrogallol derivatives (4–17) were synthesized, with their in vitro inhibitory activities against PTP1B and in vivo antihyperglycemic effects examined. Compound 14, the most potent among the series, showed a Ki value of 1.1 μM against PTP1B, 7-fold lower than that against TC-PTP. When compound 14 was fed to a high-fat diet-induced diabetic mouse model, significant improvements were observed in both the fasting glucose level and glucose tolerance.