Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B

A series of oleanolic acid (OA) derivatives have been synthesized and their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Some compounds with five-membered heterocyclic ring-fused at C-2, C-3 positions showed a dramatic increase in inhibition, the two most potent PTP1B inhibitors 19 (IC ₅₀ = 0.91 μM) and 21 (IC ₅₀ = 0.98 μM) showed about 3-fold more potent than lead compound OA. Some C-ring modified OA analogs showed high selectivity for PTP1B over TCPTP, among them, 50 possessed the best selectivity of 6.6-fold.