New amphiphilic prodrugs of adefovir and cidofovir

0361594 - ÚOCHB 2012 CZ eng C - Conference Paper (international conference)
Tichý, Tomáš - Andrei, G. - Dračínský, Martin - Holý, Antonín - Balzarini, J. - Snoeck, R. - Krečmerová, Marcela
New amphiphilic prodrugs of adefovir and cidofovir.
Chemistry of Nucleic Acid Components. 15th Symposium. Praha: Institute of Organic Chemistry and Biochemistry AS CR, v. v. i., 2011 - (Hocek, M.), s. 477-479. Collection Symposium Series, 12. ISBN 978-80-86241-37-1.
[Chemistry of Nucleic Acid Components /15./. Český Krumlov (CZ), 05.06.2011-10.06.2011]
R&D Projects: GA MŠMT 1M0508
Institutional research plan: CEZ:AV0Z40550506
Keywords : adefovir * cidofovir * antivirals * prodrugs * acyclic nucleoside phosphonate * phosphonate ester * in vitro evaluation
Subject RIV: CC - Organic Chemistry

New adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl(oxyethyl) chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The antiviral activity of the prodrugs was evaluated in vitro. A loss in the antiviral activities of the hydroxylated decyl(oxyethyl) esters and hexaethyleneglycol esters of PMEA against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anticytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir.
Permanent Link: http://hdl.handle.net/11104/0198878