Poster Presenter

O-(4-Acyloxybenzoyl) Acetaminophen Derivatives as Potential Prodrugs: Synthesis and Investigations on Physicochemical as well as Prodrugs Properties
Barbara Matuszczak, Irene Würtenberger and Thi Kim Chi Lai
Austria

The term 'prodrug' describes a compound which exhibits no or significant lower biological activity than the corresponding drug and which can be transformed into the active species in vivo by chemical and/or enzymatic hydrolysis. Prodrugs are used to improve the physicochemical, biopharmaceutical, or pharmacokinetic properties of the parent drug. Phenols are one of the most common functional groups that are amenable to prodrug design since derivatization of the phenolic function allows on the one hand to increase the lipophilicity leading to a better absorption of the drug. On the other hand, the pre-systemic metabolism will be reduced.*

Considering these findings, we have developed a series of novel potential prodrugs. Here, acetaminophen is used as an example for a drug with phenolic function and 4-acyloxy¬benzoic acids were chosen as the carrier. Since these compounds contain two ester groups, hydrolysis can result in the formation of different hydrolytic products, namely O-(4-hydroxybenzoyl)-acetaminophen, acetaminophen, 4-hydroxybenzoic acid, the appropriate 4-(acyloxy)benzoic acid as well as the corresponding aliphatic carboxylic acid. In this presentation synthesis of the novel compounds, its physicochemical properties as well as the prodrug potential will be discussed.

*J. Rautio, H. Kumpulainen, T. Heimbach, R. Oliyai, D. Oh, T. Järvinen, J. Savolainen; Nature Reviews Drug Discovery 7, 255-270 (2008)