Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Bechmann, Nicole; Kniess, Torsten; Köckerling, Martin; Pigorsch, Arne; Steinbach, Jörg; Pietzsch, Jens
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3295
• Page End: 3300
• Publication Date: 2015-08-15
• Subjects: Anti-inflammatory therapy -- Cardiovascular side effects -- Celecoxib -- Direct/indirect NO coupling -- Griess assay -- Organic nitrate; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.059
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Inhibition of cyclooxygenase-2 (COX-2) is a promising anti-inflammatory therapeutic strategy, but long-term 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 μM) and are supposed to be promising anti-inflammatory compounds with, in parallel, positive effects on vascular homeostasis.