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
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
收藏
页码:6656 / 6659
页数:4
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