methyl <(6,7-dichloro-2-ethyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy>acetate | 55507-57-8

• 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-ethyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy>acetate
• 英文别名: methyl [(6,7-dichloro-2-ethyl-1-oxo-2,3-dihydro-1H-inden-5-yl)oxy]acetate；methyl (1Oxo-2-ethyl-6,7-dichloro-5-indanyloxy)acetate；Methyl (1-oxo-2-ethyl-6,7-dichloro-5-indanyloxy)acetate；methyl 2-[(6,7-dichloro-2-ethyl-1-oxo-2,3-dihydroinden-5-yl)oxy]acetate
• CAS: 55507-57-8
• 化学式: C₁₄H₁₄Cl₂O₄
• 分子量: 317.169
• InChiKey: DLWWSPYNVOJOCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl <(6,7-dichloro-2-ethyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy>acetate 在 四氢吡咯 、 盐酸 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 溶剂黄146 、 甲苯 为溶剂， 反应 37.5h， 生成 2-(4-morpholinyl)ethyl [(5,6-dichloro-9a-ethyl-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-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
• 作为产物：
  描述：

  [(6,7-二氯-2-乙基-2,3-二氢-1-氧代-1H-茚-5-基)氧基]乙酸 、 碘甲烷 在 potassium carbonate 作用下， 以 N-甲基乙酰胺 、 水 为溶剂， 生成 methyl <(6,7-dichloro-2-ethyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy>acetate
  参考文献：
  名称：

  [5,6,9A-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoi

  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，以及它们的类似物、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因事故、缺血性中风和脑积水导致的脑部和脊髓损伤方面具有用途；也公开了用于此类用途的组合物。

  公开号：

  US04356314A1

文献信息

• [(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.

  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。这些化合物通过从多种合成途径中选择的方法合成，具体取决于特定结构、中间体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导致的大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。
• [(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。
• [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.

  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。这些化合物通过从多种合成途径中选择的方法合成，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因事故、缺血性中风和脑积水导致的脑部和脊髓损伤方面具有用途；也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]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。
• [1-Oxo-2-halo(or hydrogen) indanyloxy]-alkanoic acid
  申请人：Merck & Co., Inc.

  公开号：US04070539A1

  公开（公告）日：1978-01-24

  [1-Oxo-2-halo(or hydrogen)indanyloxy(or thio)]-alkanoic acid products and salts, esters and amide derivatives where the indanyl ring may be further substituted with from 2 to 5 nuclear substituents. The [1-oxo-2-haloindanyloxy-(or thio)]alkanoic acids are prepared (1) via the halogenation of a [1-oxoindanyloxy(or thio)]alkanoic acid or (2) via the addition of halogen to a [1-oxoindenyloxy(or thio)]-alkanoic acid. The [1-oxoindanyloxy(or thio)]alkanoic acids are prepared (1) via cyclialkylation of a (2-alkylideneacyl)-phenoxy(or thio)alkanoic acid or (2) via etherification of a hydroxy(or mercapto)-2-alkyl-1-indanone. The [1-oxo-2-halo(or hydrogen)indanyloxy(or thio)]alkanoic acids are diuretics and saluretics. In addition, some of these compounds are also able to maintain the uric acid concentration in the body at pretreatment level or to cause a decrease in uric acid concentration.

  [1-氧代-2-卤代(或氢)吲哚氧(或硫)基]-脂肪酸产物及其盐、酯和酰胺衍生物，其中吲哚环上可能进一步取代2-5个核取代基团。[1-氧代-2-卤代吲哚氧(或硫)基]-脂肪酸可通过以下方法制备：(1)将[1-氧代吲哚氧(或硫)基]-脂肪酸卤化或(2)将卤素添加到[1-氧代茚氧(或硫)基]-脂肪酸中。[1-氧代吲哚氧(或硫)基]-脂肪酸可通过以下方法制备：(1)将(2-烷基亚酰基)-苯氧(或硫)基脂肪酸環化或(2)将羟基(或巯基)-2-烷基-1-茚酮醚化。[1-氧代-2-卤代(或氢)吲哚氧(或硫)基]-脂肪酸具有利尿和盐利尿作用。此外，其中一些化合物还能够维持体内尿酸浓度在治疗前的水平或引起尿酸浓度下降。