methyl 4-[3-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]propyl]benzoate | 683813-24-3

• 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-[3-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]propyl]benzoate
• 英文别名: methyl 4-{3-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]propyl}benzoate；methyl 4-[3-(1-benzhydryl-5-chloro-2-methylindol-3-yl)propyl]benzoate
• CAS: 683813-24-3
• 化学式: C₃₃H₃₀ClNO₂
• 分子量: 508.06
• InChiKey: OJBCUOZHHGLZMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 4-[3-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]propyl]benzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以100%的产率得到4-[3-(1-Benzhydryl-5-chloro-2-methylindol-3-yl)propyl]benzoic acid
  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：

  二苯基溴甲烷 在 sodium hydride 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 1.0h， 以59%的产率得到methyl 4-[3-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]propyl]benzoate
  参考文献：
  名称：

  Process for making an aldehyde

  摘要：

  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。

  公开号：

  US20040082785A1

文献信息

• Process for the synthesis of a CPLA2 inhibitor
  申请人：Dehnhardt M. Christoph

  公开号：US20050070723A1

  公开（公告）日：2005-03-31

  A process for making a substituted indole compound, including the steps of: reacting the compounds in a non-protic polar solvent in the presence of a catalyst to form the intermediate compound wherein Ph and X are as defined herein; and then, heating this intermediate compound in the solvent in the presence of the catalyst to form the substituted indole compound The invention also includes compounds formed by this process.

  制备替代吲哚化合物的方法，包括以下步骤：在非质子极性溶剂中，在催化剂的存在下，使化合物发生反应，形成中间体化合物，其中Ph和X的定义如本文所述；然后，在溶剂中，在催化剂的存在下加热此中间体化合物，形成替代吲哚化合物。该发明还包括由此过程形成的化合物。
• 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。
• Indole Cytosolic Phospholipase A₂ α Inhibitors: Discovery and in Vitro and in Vivo Characterization of 4-{3-[5-Chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1-(diphenylmethyl)-1<i>H</i>-indol-3-yl]propyl}benzoic Acid, Efipladib
  作者：John C. McKew、Katherine L. Lee、Marina W. H. Shen、Paresh Thakker、Megan A. Foley、Mark L. Behnke、Baihua Hu、Fuk-Wah Sum、Steve Tam、Yonghan Hu、Lihren Chen、Steven J. Kirincich、Ronald Michalak、Jennifer Thomason、Manus Ipek、Kun Wu、Lane Wooder、Manjunath K. Ramarao、Elizabeth A. Murphy、Debra G. Goodwin、Leo Albert、Xin Xu、Frances Donahue、M. Sherry Ku、James Keith、Cheryl L. Nickerson-Nutter、William M. Abraham、Cara Williams、Martin Hegen、James D. Clark

  DOI：10.1021/jm701467e

  日期：2008.6.1

  The optimization of a class of indole cPLA 2 alpha inhibitors is described herein. The importance of the substituent at C3 and the substitution pattern of the phenylmethane sulfonamide region are highlighted. Optimization of these regions led to the discovery of 111 (efipladib) and 121 (WAY-196025), which are shown to be potent, selective inhibitors of cPLA 2 alpha in a variety of isolated enzyme assays

  本文描述了一类吲哚cPLA 2α抑制剂的优化。突出了C 3处取代基的重要性和苯基甲烷磺酰胺区的取代方式。这些区域的优化导致发现111（efipladib）和121（WAY-196025），在各种分离的酶测定，基于细胞的测定以及大鼠和人类中，它们被证明是有效的cPLA 2α选择性抑制剂。全血检测。这些化合物的结合已使用等温滴定热法进一步检查。最后，当在多种急性和慢性前列腺素和白三烯依赖性的体内模型中口服给药时，这些化合物显示出功效。
• Process for the Synthesis of a CPLA2 Inhibitor
  申请人：Dehnhardt Christoph M.

  公开号：US20080177085A1

  公开（公告）日：2008-07-24

  A process for making a substituted indole compound, including the steps of: reacting the compounds in a non-protic polar solvent in the presence of a catalyst to form the intermediate compound wherein Ph and X are as defined herein; and then, heating this intermediate compound in the solvent in the presence of the catalyst to form the substituted indole compound The invention also includes compounds formed by this process.

  一种制备取代吲哚化合物的方法，包括以下步骤：在非质子极性溶剂中，在催化剂的存在下反应化合物，形成中间体化合物，其中Ph和X如本文所定义；然后，在催化剂的存在下，加热该中间体化合物在溶剂中，形成取代吲哚化合物。本发明还包括由该方法形成的化合物。