methyl <<6,7-dichloro-2-ethenyl-2,3-dihydro-1-oxo-2-(3-oxobutyl)-1H-inden-5-yl>oxy>acetate | 84226-67-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: methyl <<6,7-dichloro-2-ethenyl-2,3-dihydro-1-oxo-2-(3-oxobutyl)-1H-inden-5-yl>oxy>acetate
• 英文别名: Methyl [6,7-dichloro-1-oxo-2-(3-oxo-butyl)-2-vinyl-2,3-dihydro-1H-inden-5-yl]oxy acetate；Methyl{[6,7-dichloro-1-oxo-2-(3-oxobutyl)-2-vinyl-2,3-dihydro-1H-inden-5-yl]oxy}acetate；methyl 2-[[6,7-dichloro-2-ethenyl-1-oxo-2-(3-oxobutyl)-3H-inden-5-yl]oxy]acetate
• CAS: 84226-67-5
• 化学式: C₁₈H₁₈Cl₂O₅
• 分子量: 385.244
• InChiKey: PWLCVBNCIDSYMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl <<6,7-dichloro-2-ethenyl-2,3-dihydro-1-oxo-2-(3-oxobutyl)-1H-inden-5-yl>oxy>acetate 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 [(5,6-Dichloro-3-oxo-2-vinyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)-oxy]acetic acid 、 [(5,6-dichloro-3-oxo-9a-vinyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]-acetic acid
  参考文献：
  名称：

  [(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahy

  摘要：

  该发明涉及新型[(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、中间体的选择或首选反应顺序。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部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。

  公开号：

  US04317922A1
• 作为产物：
  描述：

  [(6,7-Dichloro-2-ethylidene-1-oxo-2,3-dihydro-1H-inden-5-yl)oxy]acetic acid 在 1,5-二氮杂双环[4.3.0]壬-5-烯 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 methyl <<6,7-dichloro-2-ethenyl-2,3-dihydro-1-oxo-2-(3-oxobutyl)-1H-inden-5-yl>oxy>acetate
  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-氟烯-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部和脊髓损伤方面具有用途；同时还公开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]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.

  该发明涉及新型[(5,6,9a-取代-3-氧代-1,2,9,9a-四氢-3H-芴-7-基)氧基]烷酸和环烷酸以及它们的类似物、酯、盐和衍生物。这些化合物通过选择多种合成途径中的方法合成，具体取决于特定结构、中间体的选择或首选反应顺序。这些化合物可用于治疗和预防因事故、缺血性中风和脑积水而导致的脑部和脊髓损伤；也公开了用于这些用途的组合物。
• 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.
• [(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.

  该发明涉及新型[(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、中间体的选择或首选反应顺序。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部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。