tert-butyl N-[3-[4-(methanesulfonamido)phenyl]-5-methoxy-6-(2,2,2-trifluoroethyl)-8-quinolyl]carbamate | 1485749-24-3

• 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: tert-butyl N-[3-[4-(methanesulfonamido)phenyl]-5-methoxy-6-(2,2,2-trifluoroethyl)-8-quinolyl]carbamate
• CAS: 1485749-24-3
• 化学式: C₂₄H₂₆F₃N₃O₅S
• 分子量: 525.549
• InChiKey: IQTANDXAJSTGMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.73
• 重原子数：
  36.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  106.62
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[3-[4-(methanesulfonamido)phenyl]-5-methoxy-6-(2,2,2-trifluoroethyl)-8-quinolyl]carbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 2.0h， 以75%的产率得到N-[4-[8-amino-5-methoxy-6-(2,2,2-trifluoroethyl)-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-甲氧基-4-硝基苯甲醛 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 palladium 10% on activated carbon 、 氢气 、 溴 、 sodium hydride 、 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 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 水 、 甲苯 、 mineral oil 为溶剂， 20.0~100.0 ℃ 、379.22 kPa 条件下， 反应 12.17h， 生成 tert-butyl N-[3-[4-(methanesulfonamido)phenyl]-5-methoxy-6-(2,2,2-trifluoroethyl)-8-quinolyl]carbamate
  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