Identification of 2-substituted ethenesulfonic acid ester derivatives as novel, potent and selective inhibitors of protein tyrosine phosphatase 1B.

Sixteen 2-substituted ethenesulfonic acid ester derivatives were designed, synthesized and evaluated for the inhibitory activity against tyrosine phosphatase 1B (PTP1B) and T-Cell protein tyrosine phosphatase (TCPTP). The structural activity relationship (SAR) of these compounds demonstrated that the hydrophilic head, aromatic center and the hydrophobic tail affected the inhibitory activities against PTP1B and the selectivity over TCPTP. Most of the compounds exhibited excellent inhibitory activity against PTP1B with IC50 value of 1.0 μM - 31.2 μM. SAR analysis revealed that the hydrophilic head was indispensable in the maintain of inhibitory activity against PTP1B, the aromatic center significantly altered the selectivity of PTP1B over TCPTP, and the hydrophobic tail significantly altered the inhibitory activity against PTP1B.