DESIGN AND SYNTHESIS OF NOVEL CARBOCYCLIC VERSIONS OF 2′-SPIROCYCLOPROPYL RIBONUCLEOSIDES AS POTENT ANTI-HCV AGENTS

被引：3

作者：

Oh, Chang Hyun ^{[2
]}

Kim, Eunae ^{[1
]}

Hong, Joon Hee ^{[1
]}

机构：

[1] Chosun Univ, Coll Pharm, Project Team BK21, Kwangju 501759, South Korea

[2] Korea Inst Sci & Technol, Ctr Biomat, Seoul, South Korea

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2011年 / 30卷 / 06期

关键词：

anti-HCV agent; spirocarbocyclic nucleoside; spirocyclopropylation; 3,4-DIMETHOXYBENZYL PROTECTING GROUPS; DEPENDENT RNA-POLYMERASE; C VIRUS-REPLICATION; HEPATITIS-C; MPM; 4-METHOXYBENZYL; ANTIVIRAL ACTIVITY; CARBODINE ANALOGS; VIRAL-HEPATITIS; INHIBITORS; KETONES;

D O I：

10.1080/15257770.2011.587490

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The discovery of 2'-spirocyclopropyl-ribocytidine as a potent inhibitor of RNA synthesis by NS5B (IC(50) = 7.3 mu M), the RNA polymerase encoded by hepatitis C virus (HCV), has led to the synthesis and biological evaluation of carbocyclic versions of 2'-spiropropyl-nucleosides from cyclopentenol 6. Spirocyclopropylation of enone 7 was completed by using (2-chloroethyl)-dimethylsulfonium iodide and potassium t-butoxide to form the desired intermediate 9a. The synthesized nucleoside analogues, 18, 19, 26, and 27, were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line. The synthesized cytosine nucleoside 19 showed moderate anti-HCV activity (IC(50) = 14.4 mu M).

引用

页码：423 / 439

页数：17

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