Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors

被引：25

作者：

Bechmann, Nicole ^{[1
,2
]}

Kniess, Torsten ^{[1
]}

Koeckerling, Martin ^{[3
]}

Pigorsch, Arne ^{[3
]}

Steinbach, Joerg ^{[1
,2
]}

Pietzsch, Jens ^{[1
,2
]}

机构：

[1] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, Dept Radiopharmaceut & Chem Biol, D-01328 Dresden, Germany

[2] Tech Univ Dresden, Dept Chem & Food Chem, D-01069 Dresden, Germany

[3] Univ Rostock, Inst Chem, Inorgan Solid State Chem, D-18059 Rostock, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 16期

关键词：

Anti-inflammatory therapy; Cardiovascular side effects; Celecoxib; Direct/indirect NO coupling; Griess assay; Organic nitrate; COX-2; INHIBITORS; VASODILATOR; NITRATE; AGENTS;

D O I：

10.1016/j.bmcl.2015.05.059

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Inhibition of cyclooxygenase-2 ( COX-2) is a promising anti-inflammatory therapeutic strategy, but longterm medication with COX-2-inhibitors ( coxibs) may be associated with adverse cardiovascular effects. Functionalization of existing lead structures with nitric oxide ( NO)-releasing moieties is an auspicious approach to minimize these effects. In this regard, an organic nitrate (-O-NO2) substituent was introduced at a ( pyrazolyl) benzenesulfonamide lead structure. The novel NO-coxibs selectively inhibited COX-2 in a low micromolar range ( IC50( COX-2): 0.22-1.27 mu M) and are supposed to be promising antiinflammatory compounds with, in parallel, positive effects on vascular homeostasis. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：3295 / 3300

页数：6

共 31 条

[1]

Diazen-1-ium-1,2-diolatednitric oxide donor ester prodrugs of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids:: Synthesis, nitric oxide release studies and anti-inflammatory activities [J].