Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus

被引：63

作者：

Tsay, Shwu-Chen ^{[1
]}

Hwu, Jih Ru ^{[1
,2
,3
]}

Singha, Raghunath ^{[2
,3
]}

Huang, Wen-Chieh ^{[2
,3
]}

Chang, Yung Hsiung ^{[2
,3
]}

Hsu, Ming-Hua ^{[4
]}

Shieh, Fa-kuen ^{[1
]}

Lin, Chun-Cheng ^{[2
,3
]}

Hwang, Kuo Chu ^{[2
,3
]}

Horng, Jia-Chemg ^{[2
,3
]}

De Clercq, Erik ^{[5
]}

Vliegen, Inge ^{[5
]}

Neyts, Johan ^{[5
]}

机构：

[1] Natl Cent Univ, Dept Chem, Jhongli 32001, Taiwan

[2] Natl Tsing Hua Univ, Dept Chem, Hsinchu 30013, Taiwan

[3] Natl Tsing Hua Univ, Frontier Res Ctr Fundamental & Appl Sci Matters, Hsinchu 30013, Taiwan

[4] Natl Tsing Hua Univ, Nucl Sci & Technol Dev Ctr, Hsinchu 30013, Taiwan

[5] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 63卷

关键词：

Benzimidazole; Coumarin; Ribofuranoside; Hinged hybride; Anti-HCV; ANTICANCER ACTIVITY; ANTITUMOR-ACTIVITY; NS5B POLYMERASE; DERIVATIVES; POTENT;

D O I：

10.1016/j.ejmech.2013.02.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new compound library that contained 20 hinged benzimidazole coumarin hybrids and their beta-D-ribofuranosides was established. The anti-hepatitis C virus (HCV) activity of all novel coumarin derivatives, which were obtained by use of organic synthetic methods, was tested. Two of these hybrids exhibited appealing EC50 values of as low as 3.0 and 5.5 mu M. The best selectivity index was 14. The incorporation of a D-ribofuranose into the hinged hybrids provided the corresponding nucleosides with the beta configuration, one of which inhibited HCV replication with an EC50 value of 20 mu M. Additionally, the structure activity relationship is elucidated on the basis of the functional groups that were attached to the nuclei of benzimidazole, coumarin, and ribofuranose of the hybrids. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：290 / 298

页数：9

共 32 条

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