Literature DB >> 28626533

Synthesis and Anti-HCV Activity of a Novel 2',3'-Dideoxy-2'-α-fluoro-2'-β-C-methyl Guanosine Phosphoramidate Prodrug.

Wenquan Yu1, Ertong Li1, Zhigang Lv1, Ke Liu1, Xiaohe Guo2, Yuan Liu1, Junbiao Chang1.   

Abstract

A novel 2',3'-dideoxy-2'-α-fluoro-2'-β-C-methyl-6-methoxy guanosine (8) and its phosphoramidate prodrug (1) have been designed and synthesized. Their biological activity was evaluated in both cytotoxicity and cell-based HCV replicon assays. Neither compounds exhibited cytotoxicity up to the highest concentration tested (100 μM) in the Huh-7 cell line. The prodrug (1) displayed nanomolar level antiviral activity (EC50 = 0.39-1.1 μM) against the HCV genotype (GT) 1a, 1b, 2a, and 1b S282T replicons.

Entities:  

Keywords:  2′,3′-Dideoxy guanosine; 2′-α-fluoro-2′-β-C-methyl; NS5B RdRp inhibitor; anti-HCV activity; phosphoramidate prodrug

Year:  2017        PMID： 28626533      PMCID： PMC5467188          DOI： 10.1021/acsmedchemlett.7b00174

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  18 in total

Review 1.  Nucleotide prodrugs for the treatment of HCV infection.

Authors:  Michael J Sofia
Journal:  Adv Pharmacol       Date:  2013

Review 2.  Advances in nucleoside monophosphate prodrugs as anti-HCV agents.

Authors:  Drew R Bobeck; Raymond F Schinazi; Steven J Coats
Journal:  Antivir Ther       Date:  2010

Review 3.  Synthesis of nucleoside phosphate and phosphonate prodrugs.

Authors:  Ugo Pradere; Ethel C Garnier-Amblard; Steven J Coats; Franck Amblard; Raymond F Schinazi
Journal:  Chem Rev       Date:  2014-08-21       Impact factor: 60.622

4.  Phosphorodiamidates as a promising new phosphate prodrug motif for antiviral drug discovery: application to anti-HCV agents.

Authors:  Christopher McGuigan; Karolina Madela; Mohamed Aljarah; Claire Bourdin; Maria Arrica; Emma Barrett; Sarah Jones; Alexander Kolykhalov; Blair Bleiman; K Dawn Bryant; Babita Ganguly; Elena Gorovits; Geoffrey Henson; Damound Hunley; Jeff Hutchins; Jerry Muhammad; Aleksandr Obikhod; Joseph Patti; C Robin Walters; Jin Wang; John Vernachio; Changalvala V S Ramamurty; Srinivas K Battina; Stanley Chamberlain
Journal:  J Med Chem       Date:  2011-11-16       Impact factor: 7.446

Review 5.  Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates.

Authors:  Peter J Thornton; Hachemi Kadri; Ageo Miccoli; Youcef Mehellou
Journal:  J Med Chem       Date:  2016-09-08       Impact factor: 7.446

6.  Design, synthesis, and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methylcytidine, a potent inhibitor of hepatitis C virus replication.

Authors:  Jeremy L Clark; Laurent Hollecker; J Christian Mason; Lieven J Stuyver; Phillip M Tharnish; Stefania Lostia; Tamara R McBrayer; Raymond F Schinazi; Kyoichi A Watanabe; Michael J Otto; Phillip A Furman; Wojciech J Stec; Steven E Patterson; Krzysztof W Pankiewicz
Journal:  J Med Chem       Date:  2005-08-25       Impact factor: 7.446

7.  A 4'-C-ethynyl-2',3'-dideoxynucleoside analogue highlights the role of the 3'-OH in anti-HIV active 4'-C-ethynyl-2'-deoxy nucleosides.

Authors:  Maqbool A Siddiqui; Stephen H Hughes; Paul L Boyer; Hiroaki Mitsuya; Que N Van; Clifford George; Stefan G Sarafinanos; Victor E Marquez
Journal:  J Med Chem       Date:  2004-10-07       Impact factor: 7.446

Review 8.  Recent advances on the synthesis of hepatitis C virus NS5B RNA-dependent RNA-polymerase inhibitors.

Authors:  Can Zhao; Yinhu Wang; Shutao Ma
Journal:  Eur J Med Chem       Date:  2015-07-31       Impact factor: 6.514

9.  Discovery of the first C-nucleoside HCV polymerase inhibitor (GS-6620) with demonstrated antiviral response in HCV infected patients.

Authors:  Aesop Cho; Lijun Zhang; Jie Xu; Rick Lee; Thomas Butler; Sammy Metobo; Vangelis Aktoudianakis; Willard Lew; Hong Ye; Michael Clarke; Edward Doerffler; Daniel Byun; Ting Wang; Darius Babusis; Anne C Carey; Polina German; Dorothea Sauer; Weidong Zhong; Stephen Rossi; Martijn Fenaux; John G McHutchison; Jason Perry; Joy Feng; Adrian S Ray; Choung U Kim
Journal:  J Med Chem       Date:  2013-05-01       Impact factor: 7.446

10.  Structure-activity relationship of purine ribonucleosides for inhibition of hepatitis C virus RNA-dependent RNA polymerase.

Authors:  Anne B Eldrup; Charles R Allerson; C Frank Bennett; Sanjib Bera; Balkrishen Bhat; Neelima Bhat; Michele R Bosserman; Jennifer Brooks; Christine Burlein; Steven S Carroll; P Dan Cook; Krista L Getty; Malcolm MacCoss; Daniel R McMasters; David B Olsen; Thazha P Prakash; Marija Prhavc; Quanlai Song; Joanne E Tomassini; Jie Xia
Journal:  J Med Chem       Date:  2004-04-22       Impact factor: 7.446
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