3-acetyl-4,5-dichloro-8a-propyl-1,2,8,8a-tetrahydrocyclopentinden-6-ol | 101375-60-4

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 3-acetyl-4,5-dichloro-8a-propyl-1,2,8,8a-tetrahydrocyclopentinden-6-ol
• 英文别名: 3-acetyl-4,5-dichloro-8a-propyl-1,2,8,8a-tetrahydrocyclopent[a]inden-6-ol；1-(7,8-dichloro-6-hydroxy-3a-propyl-3,4-dihydro-2H-cyclopenta[a]inden-1-yl)ethanone
• CAS: 101375-60-4
• 化学式: C₁₇H₁₈Cl₂O₂
• 分子量: 325.235
• InChiKey: JGEAYDGGLYMERM-UHFFFAOYSA-N

物化性质

• 沸点：
  469.2±45.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.18
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  37.3
• 氢给体数：
  1.0
• 氢受体数：
  2.0

上下游信息

反应信息

• 作为反应物：
  描述：

  溴乙酸甲酯 、 3-acetyl-4,5-dichloro-8a-propyl-1,2,8,8a-tetrahydrocyclopentinden-6-ol 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.75h， 以79%的产率得到[(3-acetyl-4,5-dichloro-8a-propyl-1,2,8,8a-tetrahydrocyclopent[a]inden-6-yl)oxy]acetic acid
  参考文献：
  名称：

  Agents for the treatment of brain edema. 2. [(2,3,9,9a-Tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alkanoic acids and some of their analogs

  摘要：

  Our initial paper discussed brain edema resulting from traumatic head injury and the need for specific and effective agents to treat the disorder and disclosed a novel approach for the discovery of a drug of this kind. The current study describes the synthesis of a series of [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alk anoic acids and their analogues. These compounds were evaluated in an in vitro cerebrocortical tissue slice assay for their relative potencies in inhibiting K+ + HCO3- induced swelling. Structural modification at a number of sites in the "lead" compound revealed that significant biological activity was inherent only within a very narrow range of structural types. The observation that nearly all the biological activity resided in one of the two enantiomers demonstrated the marked stereospecificity of the most active compounds. One of the most potent compounds, (R)-(+)-[(5,6-dichloro-2,3,9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluoren -7-yl) oxy]acetic acid ((+)-5c), exhibited a dose-response relationship in the in vivo acceleration/deceleration brain edema assay, and the data from the two highest doses were statistically significant. Electron microscopic examination demonstrated that the perivascular astroglial swelling that arises from this procedure is abolished in the animals treated with (+)-5c. This compound is currently being evaluated for its clinical efficacy and safety in the treatment of traumatic head injury.

  DOI：

  10.1021/jm00155a038
• 作为产物：
  描述：

  2,3-二氯茴香醚 在 三氯化铝 、 硫酸 、 吡啶盐酸盐 、 乙酸酐 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 66.5h， 生成 3-acetyl-4,5-dichloro-8a-propyl-1,2,8,8a-tetrahydrocyclopentinden-6-ol
  参考文献：
  名称：

  Agents for the treatment of brain edema. 2. [(2,3,9,9a-Tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alkanoic acids and some of their analogs

  摘要：

  Our initial paper discussed brain edema resulting from traumatic head injury and the need for specific and effective agents to treat the disorder and disclosed a novel approach for the discovery of a drug of this kind. The current study describes the synthesis of a series of [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alk anoic acids and their analogues. These compounds were evaluated in an in vitro cerebrocortical tissue slice assay for their relative potencies in inhibiting K+ + HCO3- induced swelling. Structural modification at a number of sites in the "lead" compound revealed that significant biological activity was inherent only within a very narrow range of structural types. The observation that nearly all the biological activity resided in one of the two enantiomers demonstrated the marked stereospecificity of the most active compounds. One of the most potent compounds, (R)-(+)-[(5,6-dichloro-2,3,9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluoren -7-yl) oxy]acetic acid ((+)-5c), exhibited a dose-response relationship in the in vivo acceleration/deceleration brain edema assay, and the data from the two highest doses were statistically significant. Electron microscopic examination demonstrated that the perivascular astroglial swelling that arises from this procedure is abolished in the animals treated with (+)-5c. This compound is currently being evaluated for its clinical efficacy and safety in the treatment of traumatic head injury.

  DOI：

  10.1021/jm00155a038

文献信息

• CRAGOE E. J.;WOLTERSDORF O. W.;GOULD N. P.;PIETRUSZKIEWICZ A. M.;ZIEGLER +, J. MED. CHEM., 1986, 29, N 5, 825-841
  作者：CRAGOE E. J.、WOLTERSDORF O. W.、GOULD N. P.、PIETRUSZKIEWICZ A. M.、ZIEGLER +

  DOI：——

  日期：——