Synthesis and antiviral activity of 2′-deoxy-2′-fluoro-2′-C-methyl purine nucleosides as inhibitors of hepatitis C virus RNA replication

被引：57

作者：

Clark, JL

Mason, JC

Hollecker, L

Stuyver, LJ

Tharnish, PM

McBrayer, TR

Otto, MJ

Furman, PA

Schinazi, RF

Watanabe, KA

机构：

[1] Pharmasset Inc, Tucker, GA 30084 USA

[2] Emory Univ, Sch Med, Dept Pediat, Vet Affairs Med Ctr, Atlanta, GA 30033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 06期

关键词：

nucleosides; purines; hepatitis C; HCV;

D O I：

10.1016/j.bmcl.2005.12.002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of purine nucleosides containing the 2'-deoxy-2'-fluoro-2'-C-methylribofuranosyI moiety were synthesized and evaluated as potential inhibitors of the hepatitis C virus in vitro. Of the nucleosides that were synthesized, only those possessing a 2-amino group on the purine base reduced the levels of HCV RNA in a subgenomic replicon assay. (C) 2005 Elsevier Ltd. All rights reserved.

引用

页码：1712 / 1715

页数：4

共 10 条

[1] Inhibition of hepatitis C virus RNA replication by 2′-modified nucleoside analogs [J].

Carroll, SS ;

Tomassini, JE ;

Bosserman, M ;

Getty, K ;

Stahlhut, MW ;

Eldrup, AB ;

Bhat, B ;

Hall, D ;

Simcoe, AL ;

LaFemina, R ;

Rutkowski, CA ;

Wolanski, B ;

Yang, ZC ;

Migliaccio, G ;

De Francesco, R ;

Kuo, LC ;

MacCoss, M ;

Olsen, DB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (14) :11979-11984

[2] Design, synthesis, and antiviral activity of 2′-deoxy-2′-fluoro-2′-C-methylcytidine, a potent inhibitor of hepatitis C virus replication [J].

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

[3] Current therapy for chronic hepatitis C [J].

Davis, GL .

GASTROENTEROLOGY, 2000, 118 (02) :S104-S114

[4] Structure-activity relationship of purine ribonucleosides for inhibition of hepatitis C virus RNA-dependent RNA polymerase [J].

Eldrup, AB ;

Allerson, CR ;

Bennett, CF ;

Bera, S ;

Bhat, B ;

Bhat, N ;

Bosserman, MR ;

Brooks, J ;

Burlein, C ;

Carroll, SS ;

Cook, PD ;

Getty, KL ;

MacCoss, M ;

McMasters, DR ;

Olsen, DB ;

Prakash, TP ;

Prhavc, M ;

Song, QL ;

Tomassini, JE ;

Xia, J .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (09) :2283-2295

[5] An industrial process for synthesizing lodenosine (FddA) [J].

Izawa, K ;

Takamatsu, S ;

Katayama , S ;

Hirose, N ;

Kozai, S ;

Maruyama, T .

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2003, 22 (5-8) :507-517

[6] A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties [J].

Olsen, DB ;

Eldrup, AB ;

Bartholomew, L ;

Bhat, B ;

Bosserman, MR ;

Ceccacci, A ;

Colwell, LF ;

Fay, JF ;

Flores, OA ;

Getty, KL ;

Grobler, JA ;

LaFemina, RL ;

Markel, EJ ;

Migliaccio, G ;

Prhavc, M ;

Stahlhut, MW ;

Tomassini, JE ;

MacCoss, M ;

Hazuda, DJ ;

Carroll, SS .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (10) :3944-3953

[7] A SYNTHESIS OF 9-(2-DEOXY-2-FLUORO-BETA-D-ARABINOFURANOSYL)ADENINE AND HYPOXANTHINE - AN EFFECT OF C3'-ENDO TO C2'-ENDO CONFORMATIONAL SHIFT ON THE REACTION COURSE OF 2'-HYDROXYL GROUP WITH DAST [J].

PANKIEWICZ, KW ;

KRZEMINSKI, J ;

CISZEWSKI, LA ;

REN, WY ;

WATANABE, KA .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (02) :553-559

[8] Dynamics of subgenomic hepatitis C virus replicon RNA levels in Huh-7 cells after exposure to nucleoside antimetabolites [J].

Stuyver, LJ ;

McBrayer, TR ;

Tharnish, PM ;

Hassan, AEA ;

Chu, CK ;

Pankiewicz, KW ;

Watanabe, KA ;

Schinazi, RF ;

Otto, MJ .

JOURNAL OF VIROLOGY, 2003, 77 (19) :10689-10694

[9] Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture [J].

Stuyver, LJ ;

Whitaker, T ;

McBrayer, TR ;

Hernandez-Santiago, BI ;

Lostia, S ;

Tharnish, PM ;

Ramesh, M ;

Chu, CK ;

Jordan, R ;

Shi, JX ;

Rachakonda, S ;

Watanabe, KA ;

Otto, MJ ;

Schinazi, RF .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (01) :244-254

[10] NUCLEOSIDES OF THIOGUANINE AND OTHER 2-AMINO-6-SUBSTITUTED PURINES FROM 2-ACETAMIDO-5-CHLOROPURINE [J].

TONG, GL ;

RYAN, KJ ;

LEE, WW ;

ACTON, EM ;

GOODMAN, L .

JOURNAL OF ORGANIC CHEMISTRY, 1967, 32 (03) :859-&

← 1 →