Synthesis and pharmacological characterization of a novel nitric oxide-releasing diclofenac derivative containing a benzofuroxan moiety

1-Oxy-benzo[1,2,5]oxadiazol-5-ylmethyl [2-(2,6-dichloro-phenylamino)-phenyl]-acetate, a new diclofenac derivative bearing a benzofuroxan heterocyclic moiety in its structure, was prepared by the reaction of sodium diclofenac and 5-bromomethyl-benzo[1,2,5]oxadiazole 1-oxide. Pharmacological characterization of this modified diclofenac maintained the anti-inflammatory activity similar to its parent compound assayed in vitro and in vivo. The ulcerogenic properties of native diclofenac were not observed with this modified compound, despite the inhibition of prostaglandin E2 gastric content. The better gastric tolerability seems to be related to nitric oxide release ability.

Graphical abstractNative diclofenac (1) and benzofuroxan modified diclofenac (6). The structural modification results in anti-inflammatory activity and reduced ulcerogenic effects.Figure optionsDownload full-size imageDownload as PowerPoint slide