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Recent advances in the development of NS5B polymerase inhibitors for the treatment of hepatitis C virus infection

Pages 145-164 | Published online: 05 Feb 2009

Keep up to date with the latest research on this topic with citation updates for this article.

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Khaled Barakat, Marawan Ahmed, Yasser Tabana & Minwoo Ha. (2022) A ‘deep dive’ into the SARS-Cov-2 polymerase assembly: identifying novel allosteric sites and analyzing the hydrogen bond networks and correlated dynamics. Journal of Biomolecular Structure and Dynamics 40:19, pages 9443-9463.
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Ivan Gentile, Emanuela Zappulo, Antonio Riccardo Buonomo, Alberto Enrico Maraolo & Guglielmo Borgia. (2015) Beclabuvir for the treatment of hepatitis C. Expert Opinion on Investigational Drugs 24:8, pages 1111-1121.
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Josep Quer, Maria Buti, Maria Cubero, Jaume Guardia, Rafael Esteban & Juan Ignacio Esteban. (2010) New strategies for the treatment of hepatitis C virus infection and implications of resistance to new direct-acting antiviral agents. Infection and Drug Resistance 3, pages 133-145.
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Zhilan Zhou, Jifa Zhang, Enda Zhou, Changyu Ren, Jiaxing Wang & Yuxi Wang. (2022) Small molecule NS5B RdRp non-nucleoside inhibitors for the treatment of HCV infection: A medicinal chemistry perspective. European Journal of Medicinal Chemistry 240, pages 114595.
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J. Shen, M. Serby, A. Reed, A. J. Lee, R. Menon, X. Zhang, K. Marsh, X. Wan, O. Kavetskaia & V. Fischer. (2016) Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metabolism and Disposition 44:8, pages 1139-1147.
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Ester Sesmero & Ian Thorpe. (2015) Using the Hepatitis C Virus RNA-Dependent RNA Polymerase as a Model to Understand Viral Polymerase Structure, Function and Dynamics. Viruses 7:7, pages 3974-3994.
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Jodian A. Brown & Ian F. Thorpe. (2015) Dual Allosteric Inhibitors Jointly Modulate Protein Structure and Dynamics in the Hepatitis C Virus Polymerase. Biochemistry 54:26, pages 4131-4141.
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Rangappa S. Keri, Asha Hiremathad, Srinivasa Budagumpi & Bhari Mallanna Nagaraja. (2015) Comprehensive Review in Current Developments of Benzimidazole-Based Medicinal Chemistry. Chemical Biology & Drug Design 86:1, pages 19-65.
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Brittny C. Davis, Jodian A. Brown & Ian F. Thorpe. (2015) Allosteric Inhibitors Have Distinct Effects, but Also Common Modes of Action, in the HCV Polymerase. Biophysical Journal 108:7, pages 1785-1795.
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Pierre L. Beaulieu, Josie De Marte, Michel Garneau, Laibin Luo, Timothy Stammers, Chitra Telang, Dominik Wernic, George Kukolj & Jianmin Duan. (2015) A prodrug strategy for the oral delivery of a poorly soluble HCV NS5B thumb pocket 1 polymerase inhibitor using self-emulsifying drug delivery systems (SEDDS). Bioorganic & Medicinal Chemistry Letters 25:2, pages 210-215.
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Pierre L. Beaulieu, Paul C. Anderson, Richard Bethell, Michael Bös, Yves Bousquet, Christian Brochu, Michael G. Cordingley, Gulrez Fazal, Michel Garneau, James R. Gillard, Stephen Kawai, Martin Marquis, Ginette McKercher, Marc-André Poupart, Timothy Stammers, Bounkham Thavonekham, Dominik Wernic, Jianmin Duan & George Kukolj. (2014) Discovery of BI 207524, an Indole Diamide NS5B Thumb Pocket 1 Inhibitor with Improved Potency for the Potential Treatment of Chronic Hepatitis C Virus Infection. Journal of Medicinal Chemistry 57:23, pages 10130-10143.
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Amr H. Mahmoud, Mohamed S. A. Elsayed & Mahmoud ElHefnawi. (2012) Structure-based predictive model for some benzimidazole inhibitors of hepatitis C virus NS5B polymerase. Medicinal Chemistry Research 22:4, pages 1866-1883.
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Lenore A. Pelosi, Stacey Voss, Mengping Liu, Min Gao & Julie A. Lemm. (2012) Effect on Hepatitis C Virus Replication of Combinations of Direct-Acting Antivirals, Including NS5A Inhibitor Daclatasvir. Antimicrobial Agents and Chemotherapy 56:10, pages 5230-5239.
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Jinfa Du, Donghui Bao, Byoung-Kwon Chun, Ying Jiang, P. Ganapati Reddy, Hai-Ren Zhang, Bruce S. Ross, Shalini Bansal, Haiying Bao, Christine Espiritu, Angela M. Lam, Eisuke Murakami, Congrong Niu, Holly M. Micolochick Steuer, Phillip A. Furman, Michael J. Otto & Michael J. Sofia. (2012) β-d-2′-α-F-2′-β-C-Methyl-6-O-substituted 3′,5′-cyclic phosphate nucleotide prodrugs as inhibitors of hepatitis C virus replication: A structure–activity relationship study. Bioorganic & Medicinal Chemistry Letters 22:18, pages 5924-5929.
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Izuru Ando, Tsuyoshi Adachi, Naoki Ogura, Yukiyo Toyonaga, Kazuyuki Sugimoto, Hiroyuki Abe, Masafumi Kamada & Toru Noguchi. (2012) Preclinical Characterization of JTK-853, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase. Antimicrobial Agents and Chemotherapy 56:8, pages 4250-4256.
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Sandrine Vendeville, Tse-I. Lin, Lili Hu, Abdellah Tahri, David McGowan, Maxwell D. Cummings, Katie Amssoms, Maxime Canard, Stefaan Last, Iris Van den Steen, Benoit Devogelaere, Marie-Claude Rouan, Leen Vijgen, Jan Martin Berke, Pascale Dehertogh, Els Fransen, Erna Cleiren, Liesbet van der Helm, Gregory Fanning, Kristof Van Emelen, Origène Nyanguile, Kenny Simmen & Pierre Raboisson. (2012) Finger loop inhibitors of the HCV NS5b polymerase. Part II. Optimization of tetracyclic indole-based macrocycle leading to the discovery of TMC647055. Bioorganic & Medicinal Chemistry Letters 22:13, pages 4437-4443.
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Min Ding, Feng He, Thomas W. Hudyma, Xiaofan Zheng, Michael A. Poss, John F. Kadow, Brett R. Beno, Karen L. Rigat, Ying-Kai Wang, Robert A. Fridell, Julie A. Lemm, Dike Qiu, Mengping Liu, Stacey Voss, Lenore A. Pelosi, Susan B. Roberts, Min Gao, Jay Knipe & Robert G. Gentles. (2012) Synthesis and SAR studies of novel heteroaryl fused tetracyclic indole-diamide compounds: Potent allosteric inhibitors of the hepatitis C virus NS5B polymerase. Bioorganic & Medicinal Chemistry Letters 22:8, pages 2866-2871.
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Michael J. Sofia, Wonsuk Chang, Phillip A. Furman, Ralph T. Mosley & Bruce S. Ross. (2012) Nucleoside, Nucleotide, and Non-Nucleoside Inhibitors of Hepatitis C Virus NS5B RNA-Dependent RNA-Polymerase. Journal of Medicinal Chemistry 55:6, pages 2481-2531.
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Kevin X. Chen, Charles A. Lesburg, Bancha Vibulbhan, Weiying Yang, Tin-Yau Chan, Srikanth Venkatraman, Francisco Velazquez, Qingbei Zeng, Frank Bennett, Gopinadhan N. Anilkumar, Jose Duca, Yueheng Jiang, Patrick Pinto, Li Wang, Yuhua Huang, Oleg Selyutin, Stephen Gavalas, Haiyan Pu, Sony Agrawal, Boris Feld, Hsueh-Cheng Huang, Cheng Li, Kuo-Chi Cheng, Neng-Yang Shih, Joseph A. Kozlowski, Stuart B. Rosenblum & F. George Njoroge. (2012) A Novel Class of Highly Potent Irreversible Hepatitis C Virus NS5B Polymerase Inhibitors. Journal of Medicinal Chemistry 55:5, pages 2089-2101.
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Guanghui Yi, Jerome Deval, Baochang Fan, Hui Cai, Charlotte Soulard, C. T. Ranjith-Kumar, David B. Smith, Lawrence Blatt, Leonid Beigelman & C. Cheng Kao. (2012) Biochemical Study of the Comparative Inhibition of Hepatitis C Virus RNA Polymerase by VX-222 and Filibuvir. Antimicrobial Agents and Chemotherapy 56:2, pages 830-837.
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Kevin X. Chen, Bancha Vibulbhan, Weiying Yang, Mousumi Sannigrahi, Francisco Velazquez, Tin-Yau Chan, Srikanth Venkatraman, Gopinadhan N. Anilkumar, Qingbei Zeng, Frank Bennet, Yueheng Jiang, Charles A. Lesburg, Jose Duca, Patrick Pinto, Stephen Gavalas, Yuhua Huang, Wanli Wu, Oleg Selyutin, Sony Agrawal, Boris Feld, Hsueh-Cheng Huang, Cheng Li, Kuo-Chi Cheng, Neng-Yang Shih, Joseph A. Kozlowski, Stuart B. Rosenblum & F. George Njoroge. (2012) Structure–Activity Relationship (SAR) Development and Discovery of Potent Indole-Based Inhibitors of the Hepatitis C Virus (HCV) NS5B Polymerase. Journal of Medicinal Chemistry 55:2, pages 754-765.
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Gopinadhan N. Anilkumar, Oleg Selyutin, Stuart B. Rosenblum, Qingbei Zeng, Yueheng Jiang, Tin-Yau Chan, Haiyan Pu, Li Wang, Frank Bennett, Kevin X. Chen, Charles A. Lesburg, Jose Duca, Stephen Gavalas, Yuhua Huang, Patrick Pinto, Mousumi Sannigrahi, Francisco Velazquez, Srikanth Venkatraman, Bancha Vibulbhan, Sony Agrawal, Eric Ferrari, Chuan-kui Jiang, H.-C. Huang, Neng-Yang Shih, F. George Njoroge & Joseph A. Kozlowski. (2012) II. Novel HCV NS5B polymerase inhibitors: Discovery of indole C2 acyl sulfonamides. Bioorganic & Medicinal Chemistry Letters 22:1, pages 713-717.
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Giuseppe Manfroni, Francesco Meschini, Maria Letizia Barreca, Pieter Leyssen, Alberta Samuele, Nunzio Iraci, Stefano Sabatini, Serena Massari, Giovanni Maga, Johan Neyts & Violetta Cecchetti. (2012) Pyridobenzothiazole derivatives as new chemotype targeting the HCV NS5B polymerase. Bioorganic & Medicinal Chemistry 20:2, pages 866-876.
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Gopinadhan N. Anilkumar, Charles A. Lesburg, Oleg Selyutin, Stuart B. Rosenblum, Qingbei Zeng, Yueheng Jiang, Tin-Yau Chan, Haiyan Pu, Henry Vaccaro, Li Wang, Frank Bennett, Kevin X. Chen, Jose Duca, Stephen Gavalas, Yuhua Huang, Patrick Pinto, Mousumi Sannigrahi, Francisco Velazquez, Srikanth Venkatraman, Bancha Vibulbhan, Sony Agrawal, Nancy Butkiewicz, Boris Feld, Eric Ferrari, Zhiqing He, Chuan-kui Jiang, Robert E. Palermo, Patricia Mcmonagle, H.-C. Huang, Neng-Yang Shih, George Njoroge & Joseph A. Kozlowski. (2011) I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles. Bioorganic & Medicinal Chemistry Letters 21:18, pages 5336-5341.
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Romain Haudecoeur, Abdelhakim Ahmed-Belkacem, Wei Yi, Antoine Fortuné, Rozenn Brillet, Catherine Belle, Edwige Nicolle, Coralie Pallier, Jean-Michel Pawlotsky & Ahcène Boumendjel. (2011) Discovery of Naturally Occurring Aurones That Are Potent Allosteric Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase. Journal of Medicinal Chemistry 54:15, pages 5395-5402.
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Debasis Das, Jian Hong, Shu-Hui Chen, Guangyi Wang, Leonid Beigelman, Scott D. Seiwert & Brad O. Buckman. (2011) Recent advances in drug discovery of benzothiadiazine and related analogs as HCV NS5B polymerase inhibitors. Bioorganic & Medicinal Chemistry 19:16, pages 4690-4703.
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Pierre L. Beaulieu, James Gillard, Eric Jolicoeur, Jianmin Duan, Michel Garneau, George Kukolj & Marc-André Poupart. (2011) From benzimidazole to indole-5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase. Part 1: Indole C-2 SAR and discovery of diamide derivatives with nanomolar potency in cell-based subgenomic replicons. Bioorganic & Medicinal Chemistry Letters 21:12, pages 3658-3663.
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