N-[4-[8-amino-5-methoxy-6-(trifluoromethyl)-3-quinolyl]phenyl]methanesulfonamide | 1485749-14-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-[4-[8-amino-5-methoxy-6-(trifluoromethyl)-3-quinolyl]phenyl]methanesulfonamide
• CAS: 1485749-14-1
• 化学式: C₁₈H₁₆F₃N₃O₃S
• 分子量: 411.405
• InChiKey: RTVFGJOUXJVSPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  94.31
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-[4-[8-amino-5-methoxy-6-(trifluoromethyl)-3-quinolyl]phenyl]methanesulfonamide 、 silver cyanate 、 (2E)-3-methoxy-2-propenoyl chloride 在 硫酸 作用下， 以 N,N-二甲基甲酰胺 、 乙醇 、 水 为溶剂， 反应 3.5h， 以16%的产率得到N-[4-[8-(2,4-dioxopyrimidin-1-yl)-5-methoxy-6-(trifluoromethyl)-3-quinolyl]phenyl]methanesulfonamide
  参考文献：
  名称：

  Discovery of N-[4-[6-tert-Butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a Potent Inhibitor of the Hepatitis C Virus NS5B Polymerase

  摘要：

  In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic template with potent activity against the NS5B polymerase, a critical enzyme on the life cycle of HCV. In continuation of our exploration to improve the stilbene series, the 3,5,6,8-tetrasubstituted quinoline core was identified as replacement of the stilbene moiety. 6-Methoxy-2(1H)-pyridone was identified among several heterocyclic headgroups to have the best potency. Solubility of the template was improved by replacing a planar aryl linker with a saturated pyrrolidine. Profiling of the most promising compounds led to the identification of quinoline 41 (RG7109), which was selected for advancement to clinical development.

  DOI：

  10.1021/jm401329s
• 作为产物：
  描述：

  2-碘基-5-硝基苯甲醚 在 盐酸 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 palladium 10% on activated carbon 、 氢气 、 溴 、 铜 、 caesium carbonate 、 溶剂黄146 、 cesium fluoride 、 sodium t-butanolate 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 作用下， 以 1,4-二氧六环 、 环丁砜 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 20.0~100.0 ℃ 、393.01 kPa 条件下， 反应 74.0h， 生成 N-[4-[8-amino-5-methoxy-6-(trifluoromethyl)-3-quinolyl]phenyl]methanesulfonamide
  参考文献：
  名称：

  Discovery of N-[4-[6-tert-Butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a Potent Inhibitor of the Hepatitis C Virus NS5B Polymerase

  摘要：

  In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic template with potent activity against the NS5B polymerase, a critical enzyme on the life cycle of HCV. In continuation of our exploration to improve the stilbene series, the 3,5,6,8-tetrasubstituted quinoline core was identified as replacement of the stilbene moiety. 6-Methoxy-2(1H)-pyridone was identified among several heterocyclic headgroups to have the best potency. Solubility of the template was improved by replacing a planar aryl linker with a saturated pyrrolidine. Profiling of the most promising compounds led to the identification of quinoline 41 (RG7109), which was selected for advancement to clinical development.

  DOI：

  10.1021/jm401329s