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Bioorg Med Chem Lett. 2009 Sep 15;19(18):5297-301. doi: 10.1016/j.bmcl.2009.07.142. Epub 2009 Aug 3.

NO-NSAIDs: Gastric-sparing nitric oxide-releasable prodrugs of non-steroidal anti-inflammatory drugs.

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  • 1Pharmacology Department, Piramal Life Sciences Limited, Nirlon Complex, Goregaon East, Mumbai 400 063, India.


Recently, a new class of nitric-oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) is being studied as 'Safe NSAIDs' because of their gastric-sparing properties. As an extension of our novel disulfide linker technology, we have designed, synthesized and evaluated novel NO-releasing NSAID prodrugs such as NO-Aspirin (1b-d) and NO-Diclofenac (2b-c). Although the amide-containing derivative 1d did not show any bioavailability, the remaining compounds have shown fair to excellent pharmacokinetic, anti-inflammatory and gastric-sparing properties. Among them, however, the NO-Diclofenac (2b) has shown the most 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.

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