Discovery of 3-acetyl-4-hydroxy-2-pyranone derivatives and their difluoridoborate complexes as a novel class of HIV-1 integrase Inhibitors

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• 作者：Kavya Ramkumar ; Konstantin V. Tambov ; Rambabu Gundla ; Alex ; r V. Manaev ; Vladimir Yarovenko ; Valery F. Traven ; Nouri Neamati
• 关键词：HIV integrase inhibitor ; Boron ; Pyranone ; Docking ; GOLD ; eHITS
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：1 October 2008
• 年：2008
• 卷：16
• 期：19
• 页码：8988-8998
• 全文大小：564 K

文摘

HIV-1 integrase (IN) has emerged as an important therapeutic target for anti-HIV drug development. Its uniqueness to the virus and its critical role in the viral life cycle makes IN suitable for selective inhibition. The recent approval of Raltegravir (MK-0518) has created a surge in interest and great optimism in the field. In our ongoing IN drug design research, we herein report the discovery of substituted analogs of 3-acetyl-4-hydroxy-2-pyranones and their difluoridoborate complexes as novel IN inhibitors. In many of these compounds, complexation with boron difluoride increased the potency and selectivity of IN inhibition. Compound 9 was most active with an IC₅₀ value of 9 μM and 3 μM for 3’-processing and strand transfer inhibition, respectively.