methyl 4-[[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]ethyl]amino]benzoate | 872674-75-4

• 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-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]ethyl]amino]benzoate
• 英文别名: Methyl 4-[2-(1-benzhydryl-5-chloro-2-methylindol-3-yl)ethylamino]benzoate
• CAS: 872674-75-4
• 化学式: C₃₂H₂₉ClN₂O₂
• 分子量: 509.047
• InChiKey: CPEODMZTQSLJDS-UHFFFAOYSA-N

物化性质

• 沸点：
  709.3±60.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  43.3
• 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-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]ethyl]amino]benzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以90%的产率得到4-[2-(1-Benzhydryl-5-chloro-2-methyl-1H-indol-3-yl)-ethylamino]-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：

  乙酰丙酸乙酯 在 lithium aluminium tetrahydride 、 sodium hydride 、 sodium cyanoborohydride 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 溶剂黄146 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.67h， 生成 methyl 4-[[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]ethyl]amino]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