Chemical and biological investigation of N-hydroxy-valdecoxib:: An active metabolite of valdecoxib

被引：11

作者：

Erdelyi, Peter ^{[1
]}

Fodor, Tamas ^{[1
]}

Varga, Agnes Kis ^{[2
]}

Czugler, Matyas ^{[3
]}

Gere, Aniko ^{[2
]}

Fischer, Janos ^{[1
]}

机构：

[1] Gedeon Richter Plc, Med Chem Res Lab 4, H-1475 Budapest 10, Hungary

[2] Gedeon Richter Plc, Dept Pharmacol, H-1475 Budapest, Hungary

[3] Hungarian Acad Sci, Chem Res Ctr, Inst Struct Chem, Xray Diffract Dept, H-1025 Budapest, Hungary

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 09期

关键词：

valdecoxib analogues; cyclooxygenase-2; inhibitor; COX-2; active metabolite; non-steroidal anti-inflammatory drugs;

D O I：

10.1016/j.bmc.2008.02.088

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

The inhibition of cyclooxygenase enzymes plays an important role in the treatment of inflammatory diseases. N-Hydroxy-4-( 5-methyl-3-phenylisoxazol-4-yl) benzenesulfonamide (3)-a primary metabolite of the highly selective COX-2 inhibitor valdecoxib-was synthesized and stabilized as its monohydrate (3a center dot H(2)O). The anti-inflammatory properties of 3a H2O were investigated in carrageenan-induced edema and in acute and chronic pain models. Based on our biological investigation, we conclude that N-hydroxy-valdecoxib 3a is an active metabolite of valdecoxib. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5322 / 5330

页数：9

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