Department of Pharmaceutical Chemistry, College of Pharmacy, Omdurman Islamic University, P.O. Box 2587, Khartoum, Sudan.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Bioorg Chem. 2017 Feb;70:144-152. doi: 10.1016/j.bioorg.2016.12.005. Epub 2016 Dec 23.
The presence of free carboxylic acid group in majority of non-steroidal anti-inflammatory drug (NSAIDs) is responsible from GI irritation. Coupling of the appropriate NSAIDs (diclofenac, naproxen, dexibuprofen and meclofenamic acid) 1-4, respectively with the appropriate amino acid ester 5 using dicyclohexylcarbodiimide afforded prodrugs 6-13. The structures of the prodrugs were verified based on spectral data. Chemical hydrolysis studies performed in three different non enzymatic buffer solutions at pH 1.2, 5.5 and 7.4, as well as in 80% human plasma and 10% rat liver homogenate using HPLC indicate no conversion of prodrugs to their respective NSAID in the studied buffers, while they underwent a reasonable plasma and rat liver homogenate hydrolysis. Furthermore, ulcerogenicity of prodrugs 9 and 12 were studied and results revealed no gastro-ulcerogenic effects.
大多数非甾体抗炎药（NSAIDs）中都存在游离羧酸基团，这是引起胃肠道刺激的原因。将合适的 NSAIDs（双氯芬酸、萘普生、右旋布洛芬和甲氯芬那酸）1-4 分别与合适的氨基酸酯 5 用二环己基碳二亚胺偶联，得到前药 6-13。前药的结构基于光谱数据得到验证。在 pH 值为 1.2、5.5 和 7.4 的三种不同非酶缓冲溶液中，以及在 80%人血浆和 10%大鼠肝匀浆中进行的化学水解研究表明，在前述缓冲液中，前药没有转化为相应的 NSAID，而在前药在血浆和大鼠肝匀浆中发生了合理的水解。此外，还研究了前药 9 和 12 的致溃疡作用，结果表明它们没有胃溃疡作用。
