217493-91-9Relevant academic research and scientific papers
New prodrugs of 9-(2-phosphonomethoxyethyl) adenine [PMEA]: Synthesis and stability studies
Benzaria,Gosselin,Pelicano,Maury,Aubertin,Obert,Kirn,Imbach
, p. 563 - 565 (1995)
The synthesis, and stability in different media of new PMEA prodrugs, with S-acyl-thioethyl (SATE) as enzyme-labile phosphonate protecting groups, are described in comparison with the already known Bis(POM)- and Bis(DTE)PMEA.
Synthesis, in vitro antiviral evaluation, and stability studies of bis(s-acyl-2-thioethyl) ester derivatives of 9-[2- (phosphonomethoxy)ethyl]adenine (PMEA) as potential PMEA prodrugs with improved oral bioavailability
Benzaria, Samira,Pélicano, Hélène,Johnson, Richard,Maury, Georges,Imbach, Jean-Louis,Aubertin, Anne-Marie,Obert, Georges,Gosselin, Gilles
, p. 4958 - 4965 (2007/10/03)
A new series of hitherto unknown 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) phosphonodiester derivatives incorporating carboxyesterase-labile S- acyl-2-thioethyl (SATE) moieties as transient phosphonate-protecting groups was prepared in an attempt to increase the oral bioavailability of the antiviral agent PMEA. We report here a direct comparison of the in vitro anti-HIV and anti-HSV activities as well as the in vitro stability between the bis(SATE) derivatives and the already known PMEA prodrugs, namely, bis[(pivaloyloxy)methyl (POM)]and bis[dithiodiethy] (DTE)]PMEA. All of the compounds tested showed an enhanced in vitro antiviral activity compared to the parent PMEA. The bis(POM)- and bis(tBu-SATE)PMEA derivatives were the most effective. However, striking differences between these two compounds were found during the stability studies. In particular the bis(tBu-SATE)PMEA was found to be more stable than bis(POM)PMEA in human gastric juice and human serum, suggesting it could be considered as a promising candidate for further in vivo development.
