Inhibition of purple acid phosphatase with alpha-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 K(i) values of these compounds are as low as 4 microM, the lowest reported to date for a PAP inhibitor.
McGeary
Ross P
RP
The University of Queensland, School of Molecular and Microbial Sciences, Brisbane, Qld, Australia. r.mcgeary@uq.edu.au
Vella
Peter
P
Mak
Jeffrey Y W
JY
Guddat
Luke W
LW
Schenk
Gerhard
G
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors*; D001862:Bone Resorption / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009281:Naphthalenes; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D010024:Osteoporosis / Q000188:drug therapy
D004791:Enzyme Inhibitors; D006023:Glycoproteins; D009281:Naphthalenes; D063065:Organophosphonates; C091137:purple acid phosphatase; D000135:Acid Phosphatase