[(5,6-dichloro-3-oxo-9a-propyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]-acetic acid | 103433-13-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: [(5,6-dichloro-3-oxo-9a-propyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]-acetic acid
• 英文别名: [(5,6-Dichloro-3-oxo-9a-propyl-2,3,9,9a-tetrahydro-1H-fluoren-7-yl)oxy]acetic acid；[(5,6-dichloro-3-oxo-9a-propyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]acetic acid；2-[(3,4-dichloro-6-oxo-8a-propyl-8,9-dihydro-7H-fluoren-2-yl)oxy]acetic acid
• CAS: 103433-13-2
• 化学式: C₁₈H₁₈Cl₂O₄
• 分子量: 369.245
• InChiKey: ALFVAHDVPGFPIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(5,6-dichloro-3-oxo-9a-propyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]-acetic acid 在 盐酸 、 potassium carbonate 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 4-(3,4-Dichloro-6-oxo-8a-propyl-7,8,8a,9-tetrahydro-6H-fluoren-2-yloxy)-butyric 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：

  (6,7-Dichloro-1-oxo-2-propyl-indan-5-yloxy)-acetic acid methyl ester 在 四氢吡咯 、 盐酸 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 溶剂黄146 作用下， 以 四氢呋喃 、 溶剂黄146 、 甲苯 为溶剂， 反应 18.5h， 生成 [(5,6-dichloro-3-oxo-9a-propyl-1,2,9,9a-tetrahydro-3H-fluoren-7-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

文献信息

• [(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alka
  申请人：Merck & Co., Inc.

  公开号：US04316043A1

  公开（公告）日：1982-02-16

  The invention relates to novel [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)-oxy]alkano ic and cycloalkanoic acids and their analogs, esters, 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]脂肪酸和环脂肪酸及其类似物、酯类、盐及衍生物。这些化合物通过多种合成途径合成，具体取决于特定结构、中间体的选择或所选择的反应顺序。这些化合物可用于治疗和预防由事故、缺血性中风和脑积水引起的脑和脊髓损伤；本发明还揭示了用于此类用途的组合物。
• [(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahy
  申请人：Merck & Co., Inc.

  公开号：US04317922A1

  公开（公告）日：1982-03-02

  The invention relates to novel [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)-oxy]alkano ic and cycloalkanoic acids and their analogs, esters, 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.

  本发明涉及一种新型[(5,6,9a-取代-3-氧代-1,2,9,9a-四氢-3H-芴-7-基)-氧基]烷基和环烷基酸及其类似物、酯、盐和衍生物。这些化合物通过从多种合成途径中选择的方法合成，具体结构、中间体选择或优选反应顺序取决于合成途径。这些化合物在治疗和预防由事故、缺血性中风和脑积水引起的脑和脊髓损伤方面有用，还公开了用于这些用途的组合物。
• [(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkano
  申请人：Merck & Co., Inc.

  公开号：US04337354A1

  公开（公告）日：1982-06-29

  The invention relates to novel [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoi c and cycloalkanoic acid and their analogs, esters, 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]脂肪酸和环脂肪酸及其类似物、酯类、盐类和衍生物。这些化合物通过从多种合成途径中选择方法，根据特定的结构、中间体的选择或首选反应序列进行合成。这些化合物在治疗和预防因事故、缺血性中风和脑积水引起的脑和脊髓损伤方面有用；本发明还公开了用于此类用途的组合物。
• [(5,6,9a-substituted-3-oxo-1,2,9,9a-tet
  申请人：Merck & Co., Inc.

  公开号：US04356313A1

  公开（公告）日：1982-10-26

  The invention relates to novel [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoi c and cycloalkanoic acids and their analogs, esters, 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]脂肪酸和环脂肪酸及其类似物、酯、盐和衍生物。这些化合物通过从多种合成路线中选择的方法合成，具体取决于特定结构、中间体的选择或优选反应顺序。这些化合物在治疗和预防由事故、缺血性中风和脑积水引起的脑和脊髓损伤方面具有用途；本发明还揭示了用于此类用途的组合物。
• [5,6,9A-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoi
  申请人：Merck & Co., Inc.

  公开号：US04356314A1

  公开（公告）日：1982-10-26

  The invention relates to novel [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoi c and cycloalkanoic acids, and their analogs, esters, 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.

  本发明涉及一种新型[(5,6,9a-取代-3-氧代-1,2,9,9a-四氢-3H-芴-7-基)氧基]脂肪酸和环脂肪酸及其类似物、酯类、盐和衍生物。这些化合物是通过选择一系列合成途径中的某些方法合成的，具体取决于特定的结构、中间体的选择或首选反应序列。这些化合物在治疗和预防因事故、缺血性中风和脑积水而导致的脑和脊髓损伤方面具有用途；还公开了用于这些用途的组合物。