methyl 4-(2-(5-chloro-2-methyl-1H-indol-3-yl)ethoxy)benzoate | 479422-23-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-(2-(5-chloro-2-methyl-1H-indol-3-yl)ethoxy)benzoate
• 英文别名: methyl 4-[2-(5-chloro-2-methyl-1H-indol-3-yl)ethoxy]benzoate
• CAS: 479422-23-6
• 化学式: C₁₉H₁₈ClNO₃
• 分子量: 343.81
• InChiKey: RQHOEDVLVSMEGT-UHFFFAOYSA-N

物化性质

• 沸点：
  539.5±50.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(2-(5-chloro-2-methyl-1H-indol-3-yl)ethoxy)benzoate 在 sodium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 CDIBA
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882
• 作为产物：
  描述：

  4-(2,2-二乙氧基乙氧基)-苯甲酸甲酯 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 methyl 4-(2-(5-chloro-2-methyl-1H-indol-3-yl)ethoxy)benzoate
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882

文献信息

• Methods for the use of inhibitors of cytosolic phospholipase A2 in the treatment of thrombosis
  申请人：Clerin Valerie

  公开号：US20080009485A1

  公开（公告）日：2008-01-10

  This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds in the treating or preventing thrombosis in a mammal, or preventing progression of symptoms of thrombosis.

  这项发明提供了一种使用通式所示的取代吲哚化合物及其药用盐形式的方法。该发明提供了一种在哺乳动物中治疗或预防血栓形成，或预防血栓形成症状进展的化合物使用方法。
• Process for making an aldehyde
  申请人：Wyeth

  公开号：US20040082785A1

  公开（公告）日：2004-04-29

  A process for making an aromatic aldehyde in which a sulfoxide is reacted with a dihalogenated aromatic compound in the absence of an effective amount of an activating reagent. The aldehyde may then be used to make other compounds, such as a compound that acts as a cPLA inhibitor.

  一种制备芳香醛的过程，其中亚砜与双卤代芳香化合物在缺乏有效量活化试剂的情况下发生反应。然后可以使用该醛制备其他化合物，例如作为cPLA抑制剂的化合物。
• Discovery of Ecopladib, an Indole Inhibitor of Cytosolic Phospholipase Α₂α
  作者：Katherine L. Lee、Megan A. Foley、Lihren Chen、Mark L. Behnke、Frank E. Lovering、Steven J. Kirincich、Weiheng Wang、Jaechul Shim、Steve Tam、Marina W. H. Shen、SooPeang Khor、Xin Xu、Debra G. Goodwin、Manjunath K. Ramarao、Cheryl Nickerson-Nutter、Frances Donahue、M. Sherry Ku、James D. Clark、John C. McKew

  DOI：10.1021/jm061131z

  日期：2007.3.1

  The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha, type IVA phospholipase) are described. Inhibitors of cPLA(2)alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA(2)alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.
• [EN] INHIBITORS OF CYTOSOLIC PHOSPHOLIPASE A2<br/>[FR] INHIBITEURS DE PHOSPHOLIPASE A2 CYTOSOLIQUE
  申请人：WYETH CORP

  公开号：WO2006128142A3

  公开（公告）日：2007-03-29
• An efficient synthesis of Ecopladib
  作者：Wei Li、Jianchang Li、Dianne DeVincentis、Tarek S. Mansour

  DOI：10.1016/j.tet.2008.06.045

  日期：2008.8

  An efficient synthesis of Ecopladib, an indole inhibitor of cytosolic phospholipase A(2)alpha, is described. A new reaction involving indole C3 reductive alkylation using an acetal in the absence of water and a novel transformation of the C2 methyl to an aldehyde via dimethyl sulfoxide-mediated oxygen-transfer reaction are used in the present synthesis, which dramatically increased the synthetic efficiency. (C) 2008 Elsevier Ltd. All rights reserved.