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.NULL