(±)-(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}hexahydro-1H-inden-2(3H)-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}hexahydro-1H-inden-2(3H)-one
• 英文别名: (+/-)-(1S,3aR,7aR)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}hexahydro-1H-inden-2(3H)-one；(1S,3aR,7aR)-1-[(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethenyl]-1,3,3a,4,5,6,7,7a-octahydroinden-2-one
• 化学式: C₂₂H₂₂FNO
• 分子量: 335.421
• InChiKey: QKZZGHKUUSIDBB-HLGKFXHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (±)-(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}hexahydro-1H-inden-2(3H)-one 在 sodium tetrahydroborate 、 乙醇 作用下， 反应 6.0h， 生成 (+/-)-(1S,2S,3aR,7aR)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2(3H)-ol
  参考文献：
  名称：

  [EN] [6+5] FUSED BICYCLES AS A THROMBIN ANTAGONIST, PROCESS FOR PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE BICYCLES
  [FR] BICYCLES FUSIONNÉS [6+5] EN TANT QU'ANTAGONISTES DE LA THROMBINE, PROCÉDÉ DE PRÉPARATION DE CEUX-CI ET COMPOSITIONS PHARMACEUTIQUES CONTENANT LES BICYCLES

  摘要：

  公开号：

  WO2011162562A3
• 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 、 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 29.17h， 生成 (±)-(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}hexahydro-1H-inden-2(3H)-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

• [EN] [6+5] FUSED BICYCLES AS A THROMBIN ANTAGONIST, PROCESS FOR PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE BICYCLES<br/>[FR] BICYCLES FUSIONNÉS [6+5] EN TANT QU'ANTAGONISTES DE LA THROMBINE, PROCÉDÉ DE PRÉPARATION DE CEUX-CI ET COMPOSITIONS PHARMACEUTIQUES CONTENANT LES BICYCLES
  申请人：KOREA RES INST CHEM TECH

  公开号：WO2011162562A3

  公开（公告）日：2012-05-31
• 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.