• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Sulfur(vi) fluoride exchange as a key reaction for synthesizing biaryl sulfate core derivatives as potent hepatitis C virus NS5A inhibitors and their structure–activity relationship studies
【24h】

Sulfur(vi) fluoride exchange as a key reaction for synthesizing biaryl sulfate core derivatives as potent hepatitis C virus NS5A inhibitors and their structure–activity relationship studies

机译：氟化硫（vi）交换是合成作为有效丙型肝炎病毒NS5A抑制剂的硫酸联芳基酯核心衍生物的关键反应及其构效关系研究

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Extremely potent, new hepatitis C virus (HCV) nonstructural 5A (NS5A) featuring substituted biaryl sulfate core structures was designed and synthesized. Based on the previously reported novel HCV NS5A inhibitors featuring biaryl sulfate core structures which exhibit two-digit picomolar half-maximal effective concentration (EC _(50) ) values against HCV genotype 1b and 2a, the new inhibitors equipped with the sulfate core structures containing diversely substituted aryl groups were explored. In this study, highly efficient, chemoselective coupling reactions between an arylsulfonyl fluoride and an aryl silyl ether, known as the sulfur( VI ) fluoride exchange (SuFEx) reaction, were utilized. Among the inhibitors prepared based on the SuFEx chemistry, compounds 14 , 15 and 29 exhibited two-digit picomolar EC _(50) values against GT-1b and single digit or sub nanomolar activities against the HCV GT-2a strain. Nonsymmetrical inhibitors containing an imidazole and amide moieties on each side of the sulfate core structures were also synthesized. In addition, a biotinylated probe targeting NS5A protein was prepared for labeling using the same synthetic methodology.
机译：设计并合成了具有强大功能的新型丙型肝炎病毒（HCV）非结构性5A（NS5A），其特征在于具有取代的硫酸二芳基酯核心结构。基于先前报道的新型HCV NS5A抑制剂，其特征在于硫酸联芳基酯核心结构对HCV基因型1b和2a表现出两位数的半摩尔半最大有效浓度（EC _（50））值，新的抑制剂具有以下特征：探索了各种取代的芳基。在这项研究中，利用了芳基磺酰氟与芳基甲硅烷基醚之间的高效化学选择性偶联反应，即氟化硫（VI）交换（SuFEx）反应。在基于SuFEx化学方法制备的抑制剂中，化合物14、15和29对GT-1b表现出两位数的皮摩尔EC_（50）值，对HCV GT-2a菌株表现出一位或亚纳摩尔活性。还合成了在硫酸盐核心结构的每一侧上包含咪唑和酰胺部分的非对称抑制剂。另外，使用相同的合成方法制备了靶向NS5A蛋白的生物素化探针以进行标记。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号