Synthesis of [Difluoro-(3-alkenylphenyl)-methyl]-phosphonic acids on non-crosslinked polystyrene and Their evaluation as inhibitors of PTP1B

A series of [difluoro-(3-alkenylphenyl)-methyl]-phosphonates were prepared on non-crosslinked polystyrene, a soluble polymer support. After cleavage from the support, the resulting phosphonic acids were examined for inhibition with protein tyrosine phosphatase 1B. Compound 20, bearing an α,β-unsaturated allyl ester moiety, was the most potent of this series of compounds, being a reversible, competitive inhibitor with a Ki of 8.0±1.4 μM.