McGeary Ross P, Vella Peter, Mak Jeffrey Y W, Guddat Luke W, Schenk Gerhard
The University of Queensland, School of Molecular and Microbial Sciences, Brisbane, Qld, Australia.
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.
紫色酸性磷酸酶（PAPs）是一种双核水解酶，可催化一系列磷酸化底物的水解。人PAP是诊断骨质疏松症的主要组织化学标志物。在患有这种疾病的患者中，PAP活性会导致骨吸收增加，因此，人PAP是抗骨质疏松药物开发的关键靶点。本手稿描述了作为PAP抑制剂的1-萘基甲基膦酸衍生物的设计与合成。这些化合物的抑制常数（Ki）值低至4微摩尔，是迄今为止报道的PAP抑制剂中最低的。
