- Development of carboxylic acid replacements in indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase
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Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase enzyme has recently emerged as a viable strategy toward blocking replication of viral RNA in cell-based systems. We report here 2 series of indole-N-acetamides, bearing
- Stansfield, Ian,Pompei, Marco,Conte, Immacolata,Ercolani, Caterina,Migliaccio, Giovanni,Jairaj, Mark,Giuliano, Claudio,Rowley, Michael,Narjes, Frank
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p. 5143 - 5149
(2008/02/12)
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- Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCV NS5B polymerase: From benzimidazole to indole scaffolds
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Benzimidazole-based allosteric inhibitors of the hepatitis C virus (HCV) NS5B polymerase were diversified to a variety of topologically related scaffolds. Replacement of the polar benzimidazole core by lipophilic indoles led to inhibitors with improved potency in the cell-based subgenomic HCV replicon system. Transposing the indole scaffold into a previously described series of benzimidazole-tryptophan amides generated the most potent inhibitors of HCV RNA replication in cell culture reported to date in this series (EC50 ~ 50 nM).
- Beaulieu, Pierre L.,Gillard, James,Bykowski, Darren,Brochu, Christian,Dansereau, Nathalie,Duceppe, Jean-Simon,Hache, Bruno,Jakalian, Araz,Lagace, Lisette,LaPlante, Steven,McKercher, Ginette,Moreau, Elaine,Perreault, Stephane,Stammers, Timothy,Thauvette, Louise,Warrington, Jeff,Kukolj, George
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p. 4987 - 4993
(2007/10/03)
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- INDOLE DERIVATIVES AS ANTIVIRAL AGENTS
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The present invention relates to indole compounds of the formula (I): wherein R1, R2, R3, R4, A, E and X are as defined herein, and pharmaceutically acceptable salts thereof, useful in the prevention and treatment of hepatitis C infections.
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Page/Page column 22
(2010/10/20)
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- INDOLES AND AZAINDOLES AS ANTIVIRAL AGENTS
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The present invention relates to indoles and azaindoles of formula (I): wherein X1, X2, X3, X4, A1, Ar1, Ar, n, p and q are as defined herein and pharmaceutically acceptable salts thereof, useful in the prevention and treatment of hepatitis C virus infections.
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Page/Page column 23
(2010/02/11)
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- Development and preliminary optimization of indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase
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Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase enzyme has recently emerged as a viable strategy toward blocking replication of viral RNA in cell-based systems. We report here a novel class of allosteric inhibitor of NS5B that shows potent affinity for the NS5B enzyme and effective inhibition of subgenomic HCV RNA replication in HUH-7 cells. Inhibitors from this class have promising characteristics for further development as anti-HCV agents.
- Harper, Steven,Pacini, Barbara,Avolio, Salvatore,Di Filippo, Marcello,Migliaccio, Giovanni,Laufer, Ralph,De Francesco, Raffaele,Rowley, Michael,Narjes, Frank
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p. 1314 - 1317
(2007/10/03)
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- INDOLE ACETAMIDES AS INHIBITORS OF THE HEPATITIS C VIRUS NS5B POLYMERASE
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The present invention relates to indole and azaindole compounds of formula (I): wherein X1, X2, X3, X4, A1, Ar1, R1, R2 and n are as defined herein, and pharmaceutically acceptable salts thereof, useful in the prevention and treatment of hepatitis C infections.
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- VIRAL POLYMERASE INHIBITORS
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An isomer, enantiomer, diastereoisomer or tautomer of a compound, represented by formula (I): wherein wherein A, B, R2, R3, L, M1, M2, M3, M4, Y1, Y0, Z and Sp are as defined in claim 1, or a salt thereof, as an inhibitor of HCV NS5B polymerase.
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