ethyl 4-[1-(2,4-dimethylbenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate | 1256350-93-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 4-[1-(2,4-dimethylbenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate
• CAS: 1256350-93-2
• 化学式: C₂₃H₂₃NO₅
• 分子量: 393.439
• InChiKey: CNECHVHTMHMJPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  88.76
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-[1-(2,4-dimethylbenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以56%的产率得到4-[1-(2,4-dimethylbenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid
  参考文献：
  名称：

  Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor

  摘要：

  The search of small molecules as protein-protein interaction inhibitors represents a new attractive strategy to develop anti-HIV-1 agents. We previously reported a computational study that led to the discovery of new inhibitors of the interaction between enzyme HIV-1 integrase (IN) and the nuclear protein lens epithelium growth factor LEDGF/p75.(1)Herein, we describe new findings about the binding site of LEDGF/p75 on IN employing a different computational approach. In this way further structural requirements, helpful to disrupt LEDGF/p75-IN binding, have been identified. The main result of this work was the exploration of a relevant hydrophobic region. So we planned the introduction of suitable and simple chemical modifications on our previously reported 'hit' and the new synthesized compounds were subjected to biological tests.The results obtained demonstrate that the hydrophobic pocket could play a key role in improving inhibitory efficacy thus opening new suggestions to design active ligands. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.051
• 作为产物：
  描述：

  3-acetyl-1-(2,4-dimethylbenzyl)-4-hydroxy-1H-indole 、 草酸二乙酯 在 sodium methylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.03h， 以91%的产率得到ethyl 4-[1-(2,4-dimethylbenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate
  参考文献：
  名称：

  Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor

  摘要：

  The search of small molecules as protein-protein interaction inhibitors represents a new attractive strategy to develop anti-HIV-1 agents. We previously reported a computational study that led to the discovery of new inhibitors of the interaction between enzyme HIV-1 integrase (IN) and the nuclear protein lens epithelium growth factor LEDGF/p75.(1)Herein, we describe new findings about the binding site of LEDGF/p75 on IN employing a different computational approach. In this way further structural requirements, helpful to disrupt LEDGF/p75-IN binding, have been identified. The main result of this work was the exploration of a relevant hydrophobic region. So we planned the introduction of suitable and simple chemical modifications on our previously reported 'hit' and the new synthesized compounds were subjected to biological tests.The results obtained demonstrate that the hydrophobic pocket could play a key role in improving inhibitory efficacy thus opening new suggestions to design active ligands. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.051