Inhibition of purple acid phosphatase with alpha-alkoxynaphthylmethylphosphonic acids

Bioorg Med Chem Lett. 2009 Jan 1;19(1):163-6. doi: 10.1016/j.bmcl.2008.10.125. Epub 2008 Nov 5.


Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyse the hydrolysis of a range of phosphorylated substrates. Human PAP is a major histochemical marker for the diagnosis of osteoporosis. In patients suffering from this disorder, PAP activity contributes to increased bone resorption and, therefore, human PAP is a key target for the development of anti-osteoporotic drugs. This manuscript describes the design and synthesis of derivatives of 1-naphthylmethylphosphonic acids as inhibitors of PAP. The K(i) values of these compounds are as low as 4 microM, the lowest reported to date for a PAP inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / antagonists & inhibitors*
  • Bone Resorption / prevention & control
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Glycoproteins / antagonists & inhibitors*
  • Humans
  • Naphthalenes
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / pharmacology
  • Osteoporosis / drug therapy


  • Enzyme Inhibitors
  • Glycoproteins
  • Naphthalenes
  • Organophosphonates
  • purple acid phosphatase
  • Acid Phosphatase