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


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

Bechmann, N.; Kniess, T.; Köckerling, M.; Pigorsch, A.; Steinbach, J.; Pietzsch, J.

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 lM) and are supposed to be promising antiinflammatory compounds with, in parallel, positive effects on vascular homeostasis.

Keywords: Anti-inflammatory therapy; Cardiovascular side effects; Celecoxib; Direct/indirect NO coupling; Griess assay; Organic nitrate

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Publ.-Id: 22150