Study of triaryl-based sulfamic acid derivatives as HPTPβ inhibitors

A series of novel triaryl-based sulfamic acid analogs was designed, synthesized and evaluated as inhibitors of human protein tyrosine phosphatase beta (HPTP beta). A novel, easy and efficient synthetic method was developed for target compounds, and the activity determination results showed that most of compounds were good HPTP beta inhibitors. Interestingly, the compounds G4 and G25 with simple structure not only showed potent inhibitory activity on HPTP beta but also had good inhibitory selectivity over other PTPs (PTP1B, SHP2, LAR and TC-PTP). The molecular docking simulation of compounds with the protein HPTP beta helped us understand the structure-activity relationship and clarify some confusing assay results. This research provides references for further drug design of HPTP beta and other PTPs inhibitors.