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

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 microM) and 29 (IC(50)=0.64 microM) 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.