1393927-50-8Relevant articles and documents
NO-NSAIDs. Part 3: Nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs
Borhade, Namdev,Pathan, Asif Rahimkhan,Halder, Somnath,Karwa, Manoj,Dhiman, Mini,Pamidiboina, Venu,Gund, Machhindra,Deshattiwar, Jagannath Janardhan,Mali, Sunil Vasantrao,Deshmukh, Nitin Janardanrao,Senthilkumar, Subrayan Palanisamy,Gaikwad, Parikshit,Tipparam, Santhosh Goud,Mudgal, Jayesh,Dutta, Milan Chandra,Burhan, Aslam Usmangani,Thakre, Gajanan,Sharma, Ankur,Deshpande, Shubhada,Desai, Dattatraya Chandrakant,Dubash, Nauzer Pervez,Jain, Arun Kumar,Sharma, Somesh,Nemmani, Kumar Venkata Subrahmanya,Satyam, Apparao
experimental part, p. 465 - 481 (2012/05/31)
In continuation of our efforts to discover novel nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) as potentially "Safe NSAIDs," we report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO-releasing disulfide linker attached to a parent NSAID via linkages such as an ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25-30) or an amide (compounds 31-33). Among these NO-NSAIDs, the ester-containing NO-aspirin (9), NO-diclofenac (10), NO-naproxen (11), and the imide-containing NO-aspirin (25), NO-flurbiprofen (27) and NO-ketoprofen (28) have shown promising oral absorption, anti-inflammatory activity and NO-releasing property, and also protected rats from NSAID-induced gastric damage. NO-aspirin compound 25, on further co-evaluation with aspirin at equimolar doses, exhibited comparable dose-dependent pharmacokinetics, inhibition of gastric mucosal prostaglandin E2 (PGE2) synthesis and analgesic properties to those of aspirin, but retained its gastric-sparing properties even after doubling its oral dose. These promising NO-NSAIDs could therefore represent a new class of potentially "Safe NSAIDs" for the treatment of arthritic pain and inflammation.
