具有胃保护作用的阿司匹林和萘普生一氧化氮释放型“真正”前药。
Gastric-sparing nitric oxide-releasable 'true' prodrugs of aspirin and naproxen.
作者信息
Gund Machhindra, Gaikwad Parikshit, Borhade Namdev, Burhan Aslam, Desai Dattatraya C, Sharma Ankur, Dhiman Mini, Patil Mohan, Sheikh Javed, Thakre Gajanan, Tipparam Santhosh G, Sharma Somesh, Nemmani Kumar V S, Satyam Apparao
机构信息
Medicinal Chemistry Division, Piramal Life Sciences, Piramal Enterprises Limited, 1-Nirlon Complex, Goregaon East, Mumbai 400063, India.
Pharmacology Division, Piramal Life Sciences, Piramal Enterprises Limited, 1-Nirlon Complex, Goregaon East, Mumbai 400063, India.
出版信息
Bioorg Med Chem Lett. 2014 Dec 15;24(24):5587-5592. doi: 10.1016/j.bmcl.2014.10.096. Epub 2014 Nov 5.
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.
释放一氧化氮的非甾体抗炎药（NO-NSAIDs）作为潜在的胃保护型非甾体抗炎药正受到关注。在此，我们报告了一类新型的含“1-(硝基氧)乙酯”基团的非甾体抗炎药，它们是阿司匹林和萘普生高效释放一氧化氮的“真正”前药。一种阿司匹林前药的口服生物利用度和抗血小板活性（即抑制TXB2）与阿司匹林相当，而一种萘普生前药的生物利用度比萘普生更好。这些有前景的NO-NSAIDs可保护实验大鼠免受胃损伤。因此，我们认为这些有前景的NO-NSAIDs可能代表一类新的潜在“安全非甾体抗炎药”，用于在使用NO-阿司匹林的情况下治疗关节炎疼痛、炎症和心血管疾病。
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