Protein tyrosine phosphatase 1B (PTP1B) has been identified as a key drug target for anti-tumor drug development. Oleanolic acid (OA) has been proved to be an inhibitor of PTP1B, but its poor water solubility, low bioavailability and poor activity in vivo limit its clinical efficacy. In this study, a total of 47 new OA derivatives including heteroatom derivatives, ester derivatives, amino substitution derivatives and Schiff base derivatives were designed and synthesized. Among them, OA-Br-1 had stronger inhibition and selectivity on PTP1B than OA, with IC