New prodrugs of Adefovir and Cidofovir

0360524 - ÚOCHB 2012 RIV GB eng J - Journal Article
Tichý, Tomáš - Andrei, G. - Dračínský, Martin - Holý, Antonín - Balzarini, J. - Snoeck, R. - Krečmerová, Marcela
New prodrugs of Adefovir and Cidofovir.
Bioorganic & Medicinal Chemistry. Roč. 19, č. 11 (2011), s. 3527-3539. ISSN 0968-0896. E-ISSN 1464-3391
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
Impact factor: 2.921, year: 2011

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 occurred in comparison with the parent compound. On the other hand, the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of PMEA showed significant activities against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anti-cytomegalovirus 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/11104/0198045