Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus

咪唑-香豆素结合物抗丙型肝炎病毒的合成及构效关系

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作者:Shwu-Chen Tsay, Shu-Yu Lin, Wen-Chieh Huang, Ming-Hua Hsu, Kuo Chu Hwang, Chun-Cheng Lin, Jia-Cherng Horng, I-Chia Chen, Jih Ru Hwu, Fa-Kuen Shieh, Pieter Leyssen, Johan Neyts

Abstract

A series of new conjugated compounds with a -SCH&sub2;- linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC50 values (5.1-8.4 μM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents.

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