Lately, a new class of gastric-sparing nitric-oxide-releasable non-steroidal anti-inflammatory drugs (NO-NSAIDs) is being studied as �Safe NSAIDs�. As an extension of our novel disulfide linker technology,1 we have designed, synthesized and evaluated 25+ novel NO-NSAID prodrugs of aspirin,2 diclofenac,2 naproxen, flurbiprofen, ketoprofen, indomethacin, sulindac and ibuprofen. Although amide-containing prodrugs did not show any bioavailability or antiinflammatory activity, the remaining types of prodrugs exhibited fair to excellent pharmacokinetic, anti-inflammatory and gastric-sparing properties. Among them, however, imide-containing NO-Aspirin, NO-Flurbiprofen and NO-Ketoprofen, ester-containing NO-Diclofenac, NO-Naproxen, NO-Sulindac and NO-Ibuprofen, and double ester-containing NO-Ketoprofen have shown promising pharmacokinetic, anti-inflammatory and NO-releasing properties and protected rats from NSAID-induced gastric damage which could be attributable to the beneficial effects of NO released from these prodrugs. 1Satyam, A., Bioorg. Med. Chem. Lett., 2008, 18, 3196-3199. 2For a preliminary communication of this work, please see: Nemmani, K V S et al., Bioorg. Med. Chem. Lett., 2009, 19, 5297-5301

NO-NSAIDs: Nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs with gastric-sparing properties

240th National Meeting (2010)

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