Bioorganic & medicinal chemistry letters, 2014-12, Vol.24 (24), p.5587-5592
2014
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Details
- Autor(en) / Beteiligte
- Titel
- Gastric-sparing nitric oxide-releasable 'true' prodrugs of aspirin and naproxen
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2014-12, Vol.24 (24), p.5587-5592
- Ort / Verlag
- England
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2014.10.096Titel-ID: cdi_proquest_miscellaneous_1660390157
- Format
- –
- Schlagworte
- Animals, Anti-Inflammatory Agents, Non-Steroidal - chemistry, Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics, Anti-Inflammatory Agents, Non-Steroidal - pharmacology, Anti-Inflammatory Agents, Non-Steroidal - toxicity, Area Under Curve, Aspirin - analogs & derivatives, Aspirin - chemistry, Aspirin - pharmacokinetics, Aspirin - pharmacology, Aspirin - toxicity, Blood Platelets - drug effects, Blood Platelets - enzymology, Cyclooxygenase 1 - chemistry, Cyclooxygenase 1 - metabolism, Cyclooxygenase 2 - chemistry, Cyclooxygenase 2 - metabolism, Drug Design, Drug Stability, Gastric Mucosa - drug effects, Half-Life, Humans, Naproxen - analogs & derivatives, Naproxen - chemistry, Naproxen - pharmacokinetics, Naproxen - pharmacology, Naproxen - toxicity, Nitrates - chemistry, Nitrates - pharmacokinetics, Nitrates - pharmacology, Nitrates - toxicity, Nitric Oxide - metabolism, Platelet Aggregation Inhibitors - chemistry, Platelet Aggregation Inhibitors - pharmacokinetics, Platelet Aggregation Inhibitors - pharmacology, Platelet Aggregation Inhibitors - toxicity, Prodrugs - chemistry, Prodrugs - pharmacokinetics, Prodrugs - pharmacology, Prodrugs - toxicity, Rats, Rats, Sprague-Dawley, ROC Curve, Thromboxane B2 - metabolism