(±)-N-{(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl}methanesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (±)-N-{(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl}methanesulfonamide
• 化学式: C₂₃H₂₇FN₂O₂S
• 分子量: 414.544
• InChiKey: WORVMFGYOZJSID-DGRVINJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.65
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  59.06
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (±)-N-{(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl}methanesulfonamide 、 碘甲烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以13%的产率得到(±)-N-{(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl}-N-methylmethanesulfonamide
  参考文献：
  名称：

  Discovery of Octahydroindenes as PAR1 Antagonists

  摘要：

  Octahydroindene was identified as a novel scaffold for protease activated receptor 1 (PAR1) antagonists. Herein, the 2-position (C2) was explored for structure activity relationship (SAR) studies. Compounds 14, 19, and 23b showed IC50 values of 1.3, 8.6, and 2.7 nM in a PAR1 radioligand binding assay, respectively, and their inhibitory activities on platelet activation were comparable to that of vorapaxar in a platelet rich plasma (PRP) aggregation assay. This series of compounds showed high potency and no significant cytotoxicity; however, the compounds were metabolically unstable in both human and rat liver microsomes. Current research efforts are focused on optimizing the compounds to improve metabolic stability and physicochemical properties as well as potency.

  DOI：

  10.1021/ml400235c
• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 正丁基锂 、 sodium azide 、 potassium carbonate 、 对甲苯磺酸 、 三乙胺 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 49.17h， 生成 (±)-N-{(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl}methanesulfonamide
  参考文献：
  名称：

  Discovery of Octahydroindenes as PAR1 Antagonists

  摘要：

  Octahydroindene was identified as a novel scaffold for protease activated receptor 1 (PAR1) antagonists. Herein, the 2-position (C2) was explored for structure activity relationship (SAR) studies. Compounds 14, 19, and 23b showed IC50 values of 1.3, 8.6, and 2.7 nM in a PAR1 radioligand binding assay, respectively, and their inhibitory activities on platelet activation were comparable to that of vorapaxar in a platelet rich plasma (PRP) aggregation assay. This series of compounds showed high potency and no significant cytotoxicity; however, the compounds were metabolically unstable in both human and rat liver microsomes. Current research efforts are focused on optimizing the compounds to improve metabolic stability and physicochemical properties as well as potency.

  DOI：

  10.1021/ml400235c