期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 57, 期 13, 页码 5738-5747出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm5005804
关键词
-
资金
- Spanish Ministerio de Ciencia e Innovacion (FPU) [CTQ2011-22433]
- Spanish Ministerio de Ciencia e Innovacion (FIS) [SAF2011-27642]
- Generalitat de Catalunya (FI fellowship) [2014SGR1189]
- Government of Andorra [ATCR2012/2013-00XX-AND]
- Geconcerteerde Onderzoeksacties [GOA/10/014]
- Icrea Academia
- NIH [GM56423]
Amantadine inhibits the M2 proton channel of influenza A virus, yet most of the currently circulating strains of the virus carry mutations in the M2 protein that render the virus amantadine-resistant. While most of the research on novel amantadine analogues has revolved around the synthesis of novel adamantane derivatives, we have recently found that other polycyclic scaffolds effectively block the M2 proton channel, including amantadine-resistant mutant channels. In this work, we have synthesized and characterized a series of pyrrolidine derivatives designed as analogues of amantadine. Inhibition of the wild-type M2 channel and the A/M2-S31N, A/M2-V27A, and A/M2-L26F mutant forms of the channel were measured in Xenopus oocytes using two-electrode voltage clamp assays. Most of the novel compounds inhibited the wildtype ion channel in the low micromolar range. Of note, two of the compounds inhibited the amantadine-resistant A/M2-V27A and A/M2-L26F mutant ion channels with submicromolar and low micromolar IC50, respectively. None of the compounds was found to inhibit the S31N mutant ion channel.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据