Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B

A series of heterocyclic ring-substituted maslinic acid derivatives were prepared and subsequently evaluated on PTP1B, TCPTP and related PTPs in order to increase PTP1B inhibitory activity and especially selectivity for PTP1B over TCPTP. A series of maslinic acid derivatives have been synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Most of the compounds exhibited a dramatic increase in inhibitory potency and selectivity, the two most potent PTP1B inhibitors 20 (IC 50 = 0.61 μM) and 29 (IC 50 = 0.64 μM) showed about 10-fold more potent than lead compound maslinic acid. More importantly, 29 possesses the best selectivity of 6.9-fold for PTP1B over TCPTP.