4-(6,7-dichloro-2-cyclopentyl-2-methyl-1-oxo-indan-5-yloxymethyl)-benzoic acid | 344260-31-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 4-(6,7-dichloro-2-cyclopentyl-2-methyl-1-oxo-indan-5-yloxymethyl)-benzoic acid
• 英文别名: (+/-)-4-(6,7-Dichloro-2-cyclopentyl-2-methyl-1-oxo-indan-5-yloxymethyl)-benzoic acid；4-[(6,7-dichloro-2-cyclopentyl-2-methyl-1-oxo-3H-inden-5-yl)oxymethyl]benzoic acid
• CAS: 344260-31-7
• 化学式: C₂₃H₂₂Cl₂O₄
• 分子量: 433.331
• InChiKey: YPHXROJGPSUIEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 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：

  4-(6,7-dichloro-2-cyclopentyl-2-methyl-1-oxo-indan-5-yloxymethyl)-benzoic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-(6,7-dichloro-2-cyclopentyl-2-methyl-1-oxo-indan-5-yloxymethyl)-benzoic acid chloride
  参考文献：
  名称：

  [EN] INDANONE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  [FR] FACTEURS DE POTENTIALISATION D'INDANONE DE RÉCEPTEURS MÉTABOTROPIQUES DE GLUTAMATES

  摘要：

  本发明涉及一类潜在激活代谢型谷氨酸受体的化合物，包括mGluR2受体，这些化合物在治疗或预防与谷氨酸功能障碍相关的神经系统和精神疾病以及代谢型谷氨酸受体参与的疾病中具有用途。该发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗代谢型谷氨酸受体参与的疾病中的用途。

  公开号：

  WO2006015158A1
• 作为产物：
  描述：

  4-氯甲基苯甲酸乙酯 在 盐酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 4-(6,7-dichloro-2-cyclopentyl-2-methyl-1-oxo-indan-5-yloxymethyl)-benzoic acid
  参考文献：
  名称：

  Agents for the treatment of brain injury. 1. (Aryloxy)alkanoic acids

  摘要：

  Blunt and ischemic injuries of the brain have been shown to result in swelling that is predominantly limited to a single cell type, the astrocyte, within the complex cellular mosiac of cerebral gray matter. Evaluation of various diuretic (aryloxy)acetic acids in vitro using incubating cat brain slices and primary astrocyte cultures identified compounds with marked ability to inhibit brain tissue swelling. Some of the compounds significantly reduced the mortality and morbidity following acceleration/deceleration brain injury in anesthesized cats. A variety of (indanyloxy)alkanoic acids were synthesized which were analogous to the dually active (indanyloxy)acetic acids. Some of the 4-(indanyloxy)butanoic acids were found to be devoid of diuretic activity but to possess equal or greater activity than the dually active compounds in the in vitro and in vivo brain assays. Selected examples from both the (indanyloxy)acetic and 4-(indanyloxy)butanoic acid series showed marked chiral effects, with one enantiomer generally exhibiting a much greater activity than the other. A clinical study of severely head-injured patients treated with ethacrynic acid demonstrated a significantly improved outcome when compared to controls. These data suggest a clinical advantage for the nondiuretic (aryloxy)alkanoic acids which possess in vitro and in vivo activities in the cat brain assays that are comparable or superior to dually active compounds.

  DOI：

  10.1021/jm00347a017

文献信息

• [EN] INDANONE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] FACTEURS DE POTENTIALISATION D'INDANONE DE RÉCEPTEURS MÉTABOTROPIQUES DE GLUTAMATES
  申请人：MERCK & CO INC

  公开号：WO2006015158A1

  公开（公告）日：2006-02-09

  The present invention is directed to compounds which are potentiators of metabotropic glutamate receptors, including the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及一类潜在激活代谢型谷氨酸受体的化合物，包括mGluR2受体，这些化合物在治疗或预防与谷氨酸功能障碍相关的神经系统和精神疾病以及代谢型谷氨酸受体参与的疾病中具有用途。该发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗代谢型谷氨酸受体参与的疾病中的用途。
• Heterocyclic Acetophenone Potentiators of Metabotropic Glutamate Receptors
  申请人：Pinkerton Anthony B

  公开号：US20080293684A1

  公开（公告）日：2008-11-27

  The present invention is directed to compounds which are potentiators of metabotropic glutamate receptors, including the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及化合物，它们是代谢型谷氨酸受体的增强剂，包括mGluR2受体，可用于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及代谢型谷氨酸受体参与的疾病。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗代谢型谷氨酸受体参与的疾病方面的使用。
• Indanone Potentiators of Metabotropic Glutamate Receptors
  申请人：Pinkerton Anthony B.

  公开号：US20080312286A1

  公开（公告）日：2008-12-18

  The present invention is directed to compounds which are potentiators of metabotropic glutamate receptors, including the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及增强代谢型谷氨酸受体（包括mGluR2受体）的化合物，用于治疗或预防与谷氨酸功能障碍有关的神经和精神障碍以及涉及代谢型谷氨酸受体的疾病。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗涉及代谢型谷氨酸受体的疾病中使用这些化合物和组合物。
• CRAGOE, E. J. ,, JR;GOULD, N. P.;WOLTERSDORF, O. W. ,, JR;ZIEGLER, C., J. MED. CHEM., 1982, 25, N 5, 567-579
  作者：CRAGOE, E. J. ,, JR、GOULD, N. P.、WOLTERSDORF, O. W. ,, JR、ZIEGLER, C.

  DOI：——

  日期：——
• Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 3: Identification and biological activity of indanone containing mGlu2 receptor potentiators
  作者：Anthony B. Pinkerton、Rowena V. Cube、John H. Hutchinson、Joyce K. James、Michael F. Gardner、Blake A. Rowe、Hervé Schaffhauser、Dana E. Rodriguez、Una C. Campbell、Lorrie P. Daggett、Jean-Michel Vernier

  DOI：10.1016/j.bmcl.2005.01.077

  日期：2005.3

  We have identified and synthesized a series of phenyl-tetrazolyl and 4-thiopyridyl indanones as allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation, as well as PK properties, led to the discovery of 28 (EC50 = 186 nM), which displayed activity in a rodent model for schizophrenia. © 2005 Elsevier Ltd. All rights reserved.