Design, synthesis, and evaluation of 2-substituted ethenesulfonic acid ester derivatives as protein tyrosine phosphatase 1B inhibitors

► Thirty-two 2-substituted ethenesulfonic acid ester derivatives were prepared. ► Most compounds exhibited excellent inhibitory activities against PTP1B with IC50 values of 1.3-15.1 μM. ► The substitution at the aromatic center and the length of linker markedly affected the inhibitory activity against PTP1B. ► Most chemicals have low cytotoxicity for COS-7 cell with IC50 values >100 μM. ► Compounds 43 and 36 marked 10- and 20-fold selectivity over TCPTP respectively.