Synthesis and anti-HCV activity of 1-(1′,3′-O-anhydro-3′-C-methyl-β-D-psicofuranosyl)uracil

被引：2

作者：

Komsta, Zofia ^{[2
]}

Mayes, Benjamin ^{[1
]}

Moussa, Adel ^{[1
]}

Shelbourne, Montserrat ^{[2
]}

Stewart, Alistair ^{[1
]}

Tyrrell, Andrew J. ^{[2
]}

Wallis, Laura L. ^{[2
]}

Weymouth-Wilson, Alexander C. ^{[2
]}

Yurek-George, Alexander ^{[2
]}

机构：

[1] Idenix Pharmaceut, Cambridge, MA 02141 USA

[2] Dextra, Ctr Sci & Technol, Reading RG6 6BZ, Berks, England

来源：

TETRAHEDRON LETTERS | 2014年 / 55卷 / 45期

关键词：

HCV; Psicose; Oxetane; Bicyclic ribonucleosides; Conformational restriction; NUCLEIC-ACID; NUCLEOSIDE SYNTHESES; RIBONUCLEOSIDES; PRODRUG; ANALOGS;

D O I：

10.1016/j.tetlet.2014.09.069

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Synthesis of a novel 1',2'-oxetane-uridine bearing a 2'-C-methyl substituent, [1-(1',3'-O-anhydro-3'-Cmethyl-beta-D-psicofuranosyl)uracil], is described. Key to its construction was the use of 6-O-(p-toluoy1)1,2:3,4-di-O-isopropylidene-3-C-methyl-D-psicofuranose as a nucleosidation substrate, which itself was derived from D-fructose. Anti-HCV activity was examined for the corresponding triphosphate which was not found to be an inhibitor of HCV NS5B 1b wild type polymerase in vitro. The 1',2'-oxetane uridine triphosphate without 2'-C-methyl substitution was similarly inactive, however, the guanosine analog displayed modest inhibition (IC50= 10 mu M). (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：6216 / 6219

页数：4

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