Synthesis and biological evaluation of alpha,alpha-difluorobenzylphosphonic acid derivatives as small molecular inhibitors of protein-tyrosine phosphatase 1B

A series of alpha,alpha-difluorobenzylphosphonic acids having a hydrophobic functional group were prepared via the Stille coupling reaction from halog enated alpha,alpha-difluorobenzylphosphonates. Evaluation of inhibitory act ivity toward protein tyrosine phosphatase (PTP 1B) revealed that the ethyny l, phenylethynyl and (E)-styryl groups on the benzene nuclei increased the inhibitory activity of alpha,alpha-difluorobenzylphosphonic acid. Inhibitor y activities significantly increased upon introducing both (E)-styryl and b is-methylsulfonamide functional groups onto the benzene nuclei of alpha,alp ha-difluorobenzylphosphonic acid. (C) 1999 Elsevier Science Ltd. All rights reserved.