Synthesis of 2′-C-methylcytidine and 2′-C-methyluridine derivatives modified in the 3′-position as potential antiviral agents

被引:13
|
作者
Pierra, Claire
Amador, Agnes
Badaroux, Eric
Storer, Richard
Gosselin, Gilles
机构
[1] Univ Montpellier 2, CNRS, Lab Cooperatif Idenix, F-34095 Montpellier 5, France
[2] Labs Idenix SARL, Lab Chim Med, Cap Gamma, F-34189 Montpellier, France
关键词
pyrimidines; antivirals; hepatitis C virus; 2 '-C-methyl branched ribonucleosides; deoxygenation; fluorination; RNA viruses; nucleosides;
D O I
10.1135/cccc20060991
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
As part of our anti-hepatitis C program, we recently discovered 2'-C-methylcytidine ( 1) and 2'-C-methyluridine ( 2), which are potent inhibitors in cell culture of several viruses ( bovine viral diarrhea virus ( BVDV), yellow fever virus (YFV)) closely related to HCV. In order to characterize structure - activity relationships, we introduced some structural and functional modifications into the 3'-position of 2'-C-methylcytidine and 2'-C-methyluridine. All these hitherto unknown compounds thus synthesized were tested for the activity against a wide range of viruses and found to be inactive.
引用
收藏
页码:991 / 1010
页数:20
相关论文
共 50 条
  • [1] SYNTHESIS OF 3'-C-METHYLURIDINE AND 3'-C-METHYLCYTIDINE
    BEIGELMAN, LN
    KARPEISKY, MY
    MIKHAILOV, SN
    BIOORGANICHESKAYA KHIMIYA, 1981, 7 (11): : 1701 - 1710
  • [2] Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine
    Meppen, Malte
    Pacini, Barbara
    Bazzo, Renzo
    Koch, Uwe
    Leone, Joseph F.
    Koeplinger, Kenneth A.
    Rowley, Michael
    Altamura, Sergio
    Di Marco, Annalise
    Fiore, Fabrizio
    Giuliano, Claudio
    Gonzalez-Paz, Odalys
    Laufer, Ralph
    Pucci, Vincenzo
    Narjes, Frank
    Gardelli, Cristina
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (09) : 3765 - 3770
  • [3] HYDROLYSIS OF 2'-C-METHYLURIDINE AND 3'-C-METHYLURIDINE 2',3'-CYCLIC MONOPHOSPHATES AND INTERCONVERSION AND DEPHOSPHORYLATION OF THE RESULTING 2'-MONOPHOSPHATE AND 3'-MONOPHOSPHATE - COMPARISON WITH THE REACTIONS OF URIDINE MONOPHOSPHATES
    MIKHAILOV, SN
    OIVANEN, M
    OKSMAN, P
    LONNBERG, H
    JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (15): : 4122 - 4126
  • [4] SYNTHESIS OF 3'-C-METHYLURIDINE PHOSPHATE-ESTERS
    KARPEISKY, MY
    MIKHAILOV, SN
    PADYUKOVA, NS
    YAKOVLEV, GI
    BIOORGANICHESKAYA KHIMIYA, 1983, 9 (04): : 522 - 529
  • [5] Design, synthesis, and antiviral activity of 2′-deoxy-2′-fluoro-2′-C-methylcytidine, a potent inhibitor of hepatitis C virus replication
    Clark, JL
    Hollecker, L
    Mason, JC
    Stuyver, LJ
    Tharnish, PM
    Lostia, S
    McBrayer, TR
    Schinazi, RF
    Watanabe, KA
    Otto, MJ
    Furman, PA
    Stec, WJ
    Patterson, SE
    Pankiewiez, KW
    JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (17) : 5504 - 5508
  • [6] Phosphoramidate Prodrugs of 2′-C-Methylcytidine for Therapy of Hepatitis C Virus Infection
    Gardelli, Cristina
    Attenni, Barbara
    Donghi, Monica
    Meppen, Malte
    Pacini, Barbara
    Harper, Steven
    Di Marco, Annalise
    Fiore, Fabrizio
    Giuliano, Claudio
    Pucci, Vincenzo
    Laufer, Ralph
    Gennari, Nadia
    Marcucci, Isabella
    Leone, Joseph F.
    Olsen, David B.
    MacCoss, Malcolm
    Rowley, Michael
    Narjes, Frank
    JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (17) : 5394 - 5407
  • [7] Inhibition of norovirus replication by the nucleoside analogue 2′-C-methylcytidine
    Rocha-Pereira, J.
    Jochmans, D.
    Dallmeier, K.
    Leyssen, P.
    Cunha, R.
    Costa, I.
    Nascimento, M. S. J.
    Neyts, J.
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 427 (04) : 796 - 800
  • [8] Antiviral Efficacy upon Administration of a HepDirect Prodrug of 2′-C-Methylcytidine to Hepatitis C Virus-Infected Chimpanzees
    Carroll, Steven S.
    Koeplinger, Kenneth
    Vavrek, Marissa
    Zhang, Nanyan Rena
    Handt, Laurence
    MacCoss, Malcolm
    Olsen, David B.
    Reddy, K. Raja
    Sun, Zhili
    van Poelje, Paul D.
    Fujitaki, James M.
    Boyer, Serge H.
    Linemeyer, David L.
    Hecker, Scott J.
    Erion, Mark D.
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2011, 55 (08) : 3854 - 3860
  • [9] Pharmacokinetics of the antiviral agent β-D-2′-deoxy-2′-fluoro-2′-C-methylcytidine in rhesus monkeys
    Asif, Ghazia
    Hurwitz, Selwyn J.
    Shi, Junxing
    Hernandez-Santiago, Brenda I.
    Schinazi, Raymond F.
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (08) : 2877 - 2882
  • [10] Administration of a HepDirect™ Prodrug of 2′-C-methylcytidine to Hepatitis C Virus Infected Chimpanzees
    Carroll, Steven
    Koeplinger, Kenneth
    Vavrek, Marissa
    Handt, Laurence
    MacCoss, Malcolm
    Hecker, Scott
    Olsen, David
    ANTIVIRAL RESEARCH, 2009, 82 (02) : A22 - A22