Literature DB >> 16722622

Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site.

Ariamala Gopalsamy1, Rajiv Chopra, Kitae Lim, Gregory Ciszewski, Mengxiao Shi, Kevin J Curran, Steven F Sukits, Kristine Svenson, Joel Bard, John W Ellingboe, Atul Agarwal, Girija Krishnamurthy, Anita Y M Howe, Mark Orlowski, Boris Feld, John O'Connell, Tarek S Mansour.   

Abstract

Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.

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Year:  2006        PMID： 16722622     DOI： 10.1021/jm060168g

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  11 in total

Review 1.  Structure-function relationships among RNA-dependent RNA polymerases.

Authors:  Kenneth K S Ng; Jamie J Arnold; Craig E Cameron
Journal:  Curr Top Microbiol Immunol       Date:  2008       Impact factor: 4.291

2.  Antiviral Candidates for Treating Hepatitis E Virus Infection.

Authors:  Natalie E Netzler; Daniel Enosi Tuipulotu; Subhash G Vasudevan; Jason M Mackenzie; Peter A White
Journal:  Antimicrob Agents Chemother       Date:  2019-05-24       Impact factor: 5.191

3.  Binding-site identification and genotypic profiling of hepatitis C virus polymerase inhibitors.

Authors:  Frederik Pauwels; Wendy Mostmans; Ludo M M Quirynen; Liesbet van der Helm; Carlo W Boutton; Anne-Stéphanie Rueff; Erna Cleiren; Pierre Raboisson; Dominique Surleraux; Origène Nyanguile; Kenneth A Simmen
Journal:  J Virol       Date:  2007-04-25       Impact factor: 5.103

4.  QSAR study of C allosteric binding site of HCV NS5B polymerase inhibitors by support vector machine.

Authors:  Eslam Pourbasheer; Siavash Riahi; Mohammad Reza Ganjali; Parviz Norouzi
Journal:  Mol Divers       Date:  2010-10-08       Impact factor: 2.943

Review 5.  Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance.

Authors:  Auda A Eltahla; Fabio Luciani; Peter A White; Andrew R Lloyd; Rowena A Bull
Journal:  Viruses       Date:  2015-09-29       Impact factor: 5.048

6.  Inhibitors for the hepatitis C virus RNA polymerase explored by SAR with advanced machine learning methods.

Authors:  Iwona E Weidlich; Igor V Filippov; Jodian Brown; Neerja Kaushik-Basu; Ramalingam Krishnan; Marc C Nicklaus; Ian F Thorpe
Journal:  Bioorg Med Chem       Date:  2013-03-29       Impact factor: 3.641

7.  Classification of HCV NS5B polymerase inhibitors using support vector machine.

Authors:  Maolin Wang; Kai Wang; Aixia Yan; Changyuan Yu
Journal:  Int J Mol Sci       Date:  2012-03-27       Impact factor: 6.208

8.  Cross-genotypic examination of hepatitis C virus polymerase inhibitors reveals a novel mechanism of action for thumb binders.

Authors:  Auda A Eltahla; Enoch Tay; Mark W Douglas; Peter A White
Journal:  Antimicrob Agents Chemother       Date:  2014-09-22       Impact factor: 5.938

9.  Insight into ligand selectivity in HCV NS5B polymerase: molecular dynamics simulations, free energy decomposition and docking.

Authors:  Tong Li; Matheus Froeyen; Piet Herdewijn
Journal:  J Mol Model       Date:  2009-05-26       Impact factor: 1.810

10.  Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of thiazolone derivatives as hepatitis C virus NS5B polymerase allosteric inhibitors.

Authors:  Beilei Lei; Juan Du; Shuyan Li; Huanxiang Liu; Yueying Ren; Xiaojun Yao
Journal:  J Comput Aided Mol Des       Date:  2008-08-21       Impact factor: 3.686
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