2-[2-[(3,4-dichloro-8a-ethyl-6-oxo-8,9-dihydro-7H-fluoren-2-yl)oxy]acetyl]oxyacetic acid | 81997-20-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2-[2-[(3,4-dichloro-8a-ethyl-6-oxo-8,9-dihydro-7H-fluoren-2-yl)oxy]acetyl]oxyacetic acid
• CAS: 81997-20-8；81997-45-7
• 化学式: C₁₉H₁₈Cl₂O₆
• 分子量: 413.254
• InChiKey: NJKMOAUGSGITFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl <(6,7-dichloro-2-ethyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy>acetate 在 palladium on activated charcoal 四氢吡咯 、 盐酸 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 氢气 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 18.5h， 生成 2-[2-[(3,4-dichloro-8a-ethyl-6-oxo-8,9-dihydro-7H-fluoren-2-yl)oxy]acetyl]oxyacetic 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

文献信息

• Tetrahydro-fluorene compounds, processes for their preparation and pharmaceutical compositions thereof
  申请人：Merck & Co., Inc.

  公开号：EP0027948A1

  公开（公告）日：1981-05-06

  The invention relates to novel [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)-oxy]alkanoic and cycloalkanoic acid esters, analogs, the parent acids and their salts, and derivatives. These compounds are synthesized by methods selected from a number of synthetic routes depending on the particular structure, choice of intermediate or preferred reaction sequence. The compounds are useful in the treatment and prevention of injury to the brain and spinal chord due to accidents, ischemic stroke and hydrocephalus; compositions for such uses are also disclosed.

  本发明涉及新型[(5,6,9a-取代-3-氧代-1,2,9,9a-四氢-3H-芴-7-基)-氧基]烷酸和环烷酸酯、类似物、母酸及其盐以及衍生物。 这些化合物的合成方法可根据特定结构、中间体的选择或优选的反应顺序从多种合成路线中选择。 这些化合物可用于治疗和预防因意外事故、缺血性中风和脑积水引起的脑和脊髓损伤；本发明还公开了用于此类用途的组合物。
• 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：——
• 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
  作者：E. J. Cragoe、O. W. Woltersdorf、N. P. Gould、A. M. Pietruszkiewicz、C. Ziegler、Y. Sakurai、G. E. Stokker、P. S. Anderson、R. S. Bourke

  DOI：10.1021/jm00155a038

  日期：1986.5

  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.