Inhibition of purple acid phosphatase with α-alkoxynaphthylmethylphosphonic acids

被引：33

作者：

McGeary, Ross P. ^{[1
,2
]}

Vella, Peter ^{[1
]}

Mak, Jeffrey Y. W. ^{[1
]}

Guddat, Luke W. ^{[1
]}

Schenk, Gerhard ^{[1
]}

机构：

[1] Univ Queensland, Sch Mol & Microbial Sci, Brisbane, Qld 4072, Australia

[2] Univ Queensland, Sch Pharm, Brisbane, Qld 4072, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 01期

基金：

澳大利亚研究理事会;

关键词：

Purple acid phosphatase; PAP; Phosphonate; CRYSTAL-STRUCTURES; RECOMBINANT HUMAN; GENETIC ALGORITHM; ANION COMPLEXES; SWEET-POTATO; ACTIVE-SITE; FE-MN; UTEROFERRIN; IRON; REARRANGEMENT;

D O I：

10.1016/j.bmcl.2008.10.125

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M, the lowest reported to date for a PAP inhibitor. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：163 / 166

页数：4

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