Cyclic amide derivatives as potential prodrugs II: N-hydroxymethylsuccinimide-/isatin esters of some NSAIDs as prodrugs with an improved therapeutic index

NM Mahfouz, FA Omar, T Aboul-Fadl

Index: Mahfouz, Nadia M.; Omar, Farghaly A.; Aboul-Fadl, Tarek European Journal of Medicinal Chemistry, 1999 , vol. 34, # 7-8 p. 551 - 562

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Citation Number: 47

Abstract

Ester prodrugs of aspirin 1a, ibuprofen 1b, naproxen 1c and indomethacin 1d were synthesized using N-Hydroxymethylsuccinimide (HMSI) 3 and N-hydroxymethylisatin (HMIS) 4 as promoieties to reduce their gastrointestinal toxicity and improve bioavailability. Additionally, the kinetics of hydrolysis of the synthesized prodrugs 5a–d and 6a–d were studied at 37° C in non-enzymatic simulated gastric fluid (SGF; hydrochloric acid buffer pH ...