Adenosine Dioxolane Nucleoside Phosphoramidates as Antiviral Agents for Human Immunodeficiency and Hepatitis B Viruses.

ABSTRACT: There are currently six nucleoside reverse transcriptase inhibitors (NRTI) that are FDA approved for human clinical use and these remain the backbone of current HIV therapy. In order for these NRTIs to be effective they need to be phosphorylated consecutively by cellular kinases to their triphosphate forms. Herein, we report the synthesis of C-6 modified (-)-β-D-(2R,4R)-1,3-dioxolane adenosine nucleosides and their nucleotides including our novel phosphoramidate prodrug technology. We have introduced a side chain moiety on the phenol portion of the phosphoramidate to reduce the toxicity potential. The synthesized phosphoramidates displayed up to a 3,600-fold greater potency versus HIV-1 when compared to their corresponding parent nucleoside and were up to 300-fold more

SUBMITTER: Bondada L 

PROVIDER: S-EPMC3763849 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature