| Literature DB >> 21719300 |
Nadejda Valiaeva1, David L Wyles, Robert T Schooley, Julia B Hwu, James R Beadle, Mark N Prichard, Karl Y Hostetler.
Abstract
We reported previously that octadecyloxyethyl 9-(S)-[3-hydroxy-2-(phosphonomethoxy)-propyl]adenine (ODE-(S)-HPMPA) was active against genotype 1b and 2a hepatitis C virus (HCV) replicons. This is surprising because acyclic nucleoside phosphonates have been regarded as having antiviral activity only against double stranded DNA viruses, HIV and HBV. We synthesized octadecyloxyethyl 9-(S)-[3-methoxy-2-(phosphonomethoxy)propyl]-adenine and found it to be active in genotype 1b and 2a HCV replicons with EC₅₀ values of 1-2 μM and a CC₅₀ of > 150 μM. Analogs with substitutions at the 3'-hydroxyl larger than methyl or ethyl, or with other purine bases were less active but most compounds had significant antiviral activity against HIV-1 in vitro. The most active anti-HIV compound was octadecyloxyethyl 9-(R)-[3-methoxy-2-(phosphonomethoxy)propyl]guanine with an EC₅₀ < 0.01 nanomolar and a selectivity index of > 4.4 million.Entities:
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Year: 2011 PMID： 21719300 PMCID： PMC3139790 DOI： 10.1016/j.bmc.2011.06.009
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641