Protein–tyrosine phosphatase (PTP) inhibitors are attractive as potential signal transduction- directed therapeutics which may be useful in the treatment of a variety of diseases. We have previously reported the X-ray structure of 1, 1-difluoro-1-(2-naphthalenyl) methyl] phosphonic acid (4) complexed with the human the protein–tyrosine phosphatase 1B (PTP1B) and its use in the design of an analogue which binds with higher affinity within ...