Literature DB >> 26099532

Design, synthesis and evaluation of novel anti-HCV molecules that deliver intracellularly three highly potent NS5A inhibitors.

Sebastien Boucle1, Sijia Tao1, Franck Amblard1, Richard A Stanton1, James H Nettles1, Chengwei Li1, Tamara R McBrayer2, Tony Whitaker2, Steven J Coats2, Raymond F Schinazi3.   

Abstract

The design and synthesis of new non-symmetrical NS5A inhibitors with sulfur containing amino acids is reported along with their ability to block HCV replication in an HCV 1b replicon system. These compounds display EC50 values in the picomolar range with a large therapeutic index (>10(6)). Moreover, cellular pharmacology studies show that our preferred compounds intracellularly deliver three potent NS5A inhibitors. Published by Elsevier Ltd.

Entities:  

Keywords:  Antiviral; HCV; NS5A

Mesh：

Substances：

Year:  2015        PMID： 26099532      PMCID： PMC4538959          DOI： 10.1016/j.bmcl.2015.06.031

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  16 in total

Review 1.  Hepatitis C virus resistance to protease inhibitors.

Authors:  Philippe Halfon; Stephen Locarnini
Journal:  J Hepatol       Date:  2011-02-01       Impact factor: 25.083

2.  Novel spiroketal pyrrolidine GSK2336805 potently inhibits key hepatitis C virus genotype 1b mutants: from lead to clinical compound.

Authors:  Wieslaw M Kazmierski; Andrew Maynard; Maosheng Duan; Sam Baskaran; Janos Botyanszki; Renae Crosby; Scott Dickerson; Matthew Tallant; Rick Grimes; Robert Hamatake; Martin Leivers; Christopher D Roberts; Jill Walker
Journal:  J Med Chem       Date:  2014-02-26       Impact factor: 7.446

3.  Metabolism of sulfinpyrazone sulfide and sulfinpyrazone by human liver microsomes and cDNA-expressed cytochrome P450s.

Authors:  M He; A E Rettie; J Neal; W F Trager
Journal:  Drug Metab Dispos       Date:  2001-05       Impact factor: 3.922

4.  Studies on the metabolism and biological activity of the epimers of sulindac.

Authors:  David Brunell; Daphna Sagher; Shailaja Kesaraju; Nathan Brot; Herbert Weissbach
Journal:  Drug Metab Dispos       Date:  2011-03-07       Impact factor: 3.922

Review 5.  Chronic hepatitis C and genotyping: the clinical significance of determining HCV genotypes.

Authors:  H James Hnatyszyn
Journal:  Antivir Ther       Date:  2005

6.  Synthesis and biological evaluation of new potent and selective HCV NS5A inhibitors.

Authors:  Junxing Shi; Longhu Zhou; Franck Amblard; Drew R Bobeck; Hongwang Zhang; Peng Liu; Lavanya Bondada; Tamara R McBrayer; Phillip M Tharnish; Tony Whitaker; Steven J Coats; Raymond F Schinazi
Journal:  Bioorg Med Chem Lett       Date:  2012-03-29       Impact factor: 2.823

7.  Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A.

Authors:  David A DeGoey; John T Randolph; Dachun Liu; John Pratt; Charles Hutchins; Pamela Donner; A Chris Krueger; Mark Matulenko; Sachin Patel; Christopher E Motter; Lissa Nelson; Ryan Keddy; Michael Tufano; Daniel D Caspi; Preethi Krishnan; Neeta Mistry; Gennadiy Koev; Thomas J Reisch; Rubina Mondal; Tami Pilot-Matias; Yi Gao; David W A Beno; Clarence J Maring; Akhter Molla; Emily Dumas; Andrew Campbell; Laura Williams; Christine Collins; Rolf Wagner; Warren M Kati
Journal:  J Med Chem       Date:  2014-01-15       Impact factor: 7.446

8.  Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.

Authors:  John O Link; James G Taylor; Lianhong Xu; Michael Mitchell; Hongyan Guo; Hongtao Liu; Darryl Kato; Thorsten Kirschberg; Jianyu Sun; Neil Squires; Jay Parrish; Terry Kellar; Zheng-Yu Yang; Chris Yang; Mike Matles; Yujin Wang; Kelly Wang; Guofeng Cheng; Yang Tian; Erik Mogalian; Elsa Mondou; Melanie Cornpropst; Jason Perry; Manoj C Desai
Journal:  J Med Chem       Date:  2014-01-10       Impact factor: 7.446

9.  Synthesis and evaluation of non-dimeric HCV NS5A inhibitors.

Authors:  Franck Amblard; Hongwang Zhang; Longhu Zhou; Junxing Shi; Drew R Bobeck; James H Nettles; Satish Chavre; Tamara R McBrayer; Philip Tharnish; Tony Whitaker; Steven J Coats; Raymond F Schinazi
Journal:  Bioorg Med Chem Lett       Date:  2013-02-13       Impact factor: 2.823

10.  Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir.

Authors:  Chunfu Wang; Jin-Hua Sun; Donald R O'Boyle; Peter Nower; Lourdes Valera; Susan Roberts; Robert A Fridell; Min Gao
Journal:  Antimicrob Agents Chemother       Date:  2013-02-12       Impact factor: 5.191
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