doi: 10.1016/j.bmcl.2010.08.135.
Epub 2010 Sep 24.
Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold
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- PMID: 20869872
- DOI: 10.1016/j.bmcl.2010.08.135
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Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold
Bioorg Med Chem Lett.
.
Abstract
Optimization studies using an HIV RNase H active site inhibitor containing a 1-hydroxy-1,8-naphthyridin-2(1H)-one core identified 4-position substituents that provided several potent and selective inhibitors. The best compound was potent and selective in biochemical assays (IC(50)=0.045 μM, HIV RT RNase H; 13 μM, HIV RT-polymerase; 24 μM, HIV integrase) and showed antiviral efficacy in a single-cycle viral replication assay in P4-2 cells (IC(50)=0.19 μM) with a modest window with respect to cytotoxicity (CC(50)=3.3 μM).
Copyright © 2010 Elsevier Ltd. All rights reserved.
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