Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold

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• 作者：Peter D. Williams ; Donnette D. Staas ; Shankar Venkatraman ; H. Marie Loughran ; Rowena D. Ruzek ; Theresa M. Booth ; Terry A. Lyle ; John S. Wai ; Joseph P. Vacca ; Bradley P. Feuston ; Linda T. Ecto ; Jessica
• 关键词：HIV ; Reverse transcriptase ; RNase H inhibitor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 November 2010
• 年：2010
• 卷：20
• 期：22
• 页码：6754-6757
• 全文大小：320 K

文摘

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 (IC₅₀ = 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 (IC₅₀ = 0.19 μM) with a modest window with respect to cytotoxicity (CC₅₀ = 3.3 μM).