Literature DB >> 19507864

Structure-based design of a benzodiazepine scaffold yields a potent allosteric inhibitor of hepatitis C NS5B RNA polymerase.

Koen Vandyck1, Maxwell D Cummings, Origène Nyanguile, Carlo W Boutton, Sandrine Vendeville, David McGowan, Benoit Devogelaere, Katie Amssoms, Stefaan Last, Klara Rombauts, Abdellah Tahri, Pedro Lory, Lili Hu, Derek A Beauchamp, Kenny Simmen, Pierre Raboisson.   

Abstract

HCV NS5B polymerase, an essential and virus-specific enzyme, is an important target for drug discovery. Using structure-based design, we optimized a 1,5-benzodiazepine NS5B polymerase inhibitor chemotype into a new sulfone-containing scaffold. The design yielded potent inhibitor (S)-4c (K(D) = 0.79 nM), which has approximately 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.

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Year:  2009        PMID： 19507864     DOI： 10.1021/jm9005548

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


  8 in total

Review 1.  Privileged diazepine compounds and their emergence as bromodomain inhibitors.

Authors:  Steven G Smith; Roberto Sanchez; Ming-Ming Zhou
Journal:  Chem Biol       Date:  2014-04-17

2.  Inhibitors of foot and mouth disease virus targeting a novel pocket of the RNA-dependent RNA polymerase.

Authors:  Ryan C Durk; Kamalendra Singh; Ceili A Cornelison; Devendra K Rai; Kayla B Matzek; Maxwell D Leslie; Elizabeth Schafer; Bruno Marchand; Adeyemi Adedeji; Eleftherios Michailidis; Christopher A Dorst; Jennifer Moran; Christie Pautler; Luis L Rodriguez; Mark A McIntosh; Elizabeth Rieder; Stefan G Sarafianos
Journal:  PLoS One       Date:  2010-12-21       Impact factor: 3.240

3.  Design, Synthesis and Fungicidal Activity of 2-Substituted Phenyl-2-oxo-, 2-Hydroxy- and 2-Acyloxyethylsulfonamides.

Authors:  Minlong Wang; Peng Rui; Caixiu Liu; Ying Du; Peiwen Qin; Zhiqiu Qi; Mingshan Ji; Xinghai Li; Zining Cui
Journal:  Molecules       Date:  2017-05-04       Impact factor: 4.411

4.  Novel chemical starting points for drug discovery in leishmaniasis and Chagas disease.

Authors:  Irene Roquero; Juan Cantizani; Ignacio Cotillo; M Pilar Manzano; Albane Kessler; J Julio Martín; Case W McNamara
Journal:  Int J Parasitol Drugs Drug Resist       Date:  2019-05-22       Impact factor: 4.077

5.  TMC647055, a potent nonnucleoside hepatitis C virus NS5B polymerase inhibitor with cross-genotypic coverage.

Authors:  Benoit Devogelaere; Jan Martin Berke; Leen Vijgen; Pascale Dehertogh; Els Fransen; Erna Cleiren; Liesbet van der Helm; Origène Nyanguile; Abdellah Tahri; Katie Amssoms; Oliver Lenz; Maxwell D Cummings; Reginald F Clayton; Sandrine Vendeville; Pierre Raboisson; Kenneth A Simmen; Gregory C Fanning; Tse-I Lin
Journal:  Antimicrob Agents Chemother       Date:  2012-06-18       Impact factor: 5.191

6.  1a/1b subtype profiling of nonnucleoside polymerase inhibitors of hepatitis C virus.

Authors:  Origène Nyanguile; Benoit Devogelaere; Leen Vijgen; Walter Van den Broeck; Frederik Pauwels; Maxwell D Cummings; Hendrik L De Bondt; Ann M Vos; Jan M Berke; Oliver Lenz; Geneviève Vandercruyssen; Katrien Vermeiren; Wendy Mostmans; Pascale Dehertogh; Frédéric Delouvroy; Sandrine Vendeville; Koen VanDyck; Koen Dockx; Erna Cleiren; Pierre Raboisson; Kenneth A Simmen; Gregory C Fanning
Journal:  J Virol       Date:  2010-01-13       Impact factor: 5.103

7.  Multiple virtual screening approaches for finding new hepatitis C virus RNA-dependent RNA polymerase inhibitors: structure-based screens and molecular dynamics for the pursue of new poly pharmacological inhibitors.

Authors:  Mahmoud Elhefnawi; Mohammad ElGamacy; Mohamed Fares
Journal:  BMC Bioinformatics       Date:  2012-12-13       Impact factor: 3.169

8.  Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking.

Authors:  Yu Wei; Jinlong Li; Jie Qing; Mingjie Huang; Ming Wu; Fenghua Gao; Dongmei Li; Zhangyong Hong; Lingbao Kong; Weiqiang Huang; Jianping Lin
Journal:  PLoS One       Date:  2016-02-04       Impact factor: 3.240
  8 in total

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