Efficient synthesis and in vitro cytostatic activity of 4-substituted triazolyl-nucleosides

被引：99

作者：

El Akri, Khalid ^{[1
,2
]}

Bougrin, Khalid ^{[2
]}

Balzarini, Jan ^{[3
]}

Faraj, Abdesslem ^{[4
]}

Benhida, Rachid ^{[1
]}

机构：

[1] Univ Nice Sophia Antipolis, Inst Chim Nice, UMR CNRS 6001, Lab Chim Mol Bioactives & Aromes, F-06108 Nice 2, France

[2] Univ Mohammed V Agdal, Fac Sci, Lab Chim Plantes Synthese Organ & Bioorgan, Rabat, Morocco

[3] Katholieke Univ Leuven, Rega Inst Med Res, BE-3000 Louvain, Belgium

[4] Theravia EFS, F-34095 Montpellier, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 23期

关键词：

nucleosides; microwave; antitumor; cycloaddition;

D O I：

10.1016/j.bmcl.2007.08.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report herein an efficient synthesis of 4-substituted triazolyl-nucleosides and their in vitro cytostatic activity. The synthesis is based on a straightforward 1,3-dipolar cycloaddition between 1-azido-ribose 2 and terminal alkynes under a cooperative effect of microwave activation and copper (I) catalysis. All cycloadducts were obtained in nearly quantitative yield after a short reaction time (1 to 2 min). After removal of acetyl protecting groups, the free nucleosides were evaluated against L1210, Molt4/C8, and CEM tumor cell lines. Structure - activity relationship study shows that the substituent on the triazole ring has a major effect since nucleosides 4c and 4g, containing, respectively, a long alkyl chain and an aryl donor group are the most active compounds in this series. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：6656 / 6659

页数：4

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