α,α-Difluoro-β-ketophosphonates as potent inhibitors of protein tyrosine phosphatase 1B

A novel series of inhibitors that contain an aryl α,α-difluoro-β-ketophosphonate group has been synthesized and evaluated against protein tyrosine phosphatase 1B. These compounds exhibit strong inhibitory activity, the best of which has a Ki value of 0.17 μM. These results demonstrate that aryl α,α-difluoro-β-ketophosphonates are powerful phosphotyrosine mimetics for the development of potent PTP inhibitors.