Inhibition of purple acid phosphatase with α-alkoxynaphthylmethylphosphonic acids

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 Ki values of these compounds are as low as 4 μM, the lowest reported to date for a PAP inhibitor.

Graphical abstractThe design and synthesis of potent inhibitors of purple acid phosphatase are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide