(±)-(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydrospiro(indene-2,5'-oxazolidin)-2’-one

• 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: (±)-(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydrospiro(indene-2,5'-oxazolidin)-2’-one
• 化学式: C₂₄H₂₅FN₂O₂
• 分子量: 392.473
• InChiKey: YFICELBHPPRCPC-XLRSUNBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.21
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  51.22
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 吡啶 、 四(三苯基膦)钯 、 正丁基锂 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 28.17h， 生成 (±)-(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydrospiro(indene-2,5'-oxazolidin)-2’-one
  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

文献信息

• Discovery of Octahydroindenes as PAR1 Antagonists
  作者：Sunkyung Lee、Jong-Hwan Song、Chul Min Park、Jin-Seok Kim、Ji-Hye Jeong、Woo-Young Cho、Dong-Chul Lim

  DOI：10.1021/ml400235c

  日期：2013.11.14

  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.