4-[1-(3,5-dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid | 1351646-52-0

• 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: 4-[1-(3,5-dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid
• CAS: 1351646-52-0
• 化学式: C₂₂H₂₁NO₅
• 分子量: 379.412
• InChiKey: KIGQEPSBAHCQOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.02
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  88.76
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  3-acetyl-1-(3,5-dimethylbenzyl)-4-methoxy-1H-indole 在 sodium methylate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.53h， 生成 4-[1-(3,5-dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid
  参考文献：
  名称：

  小分子的微波辅助有机合成 (MAOS) 作为潜在的 HIV-1 整合酶抑制剂。

  摘要：

  Integrase (IN) 代表了开发针对人类免疫缺陷病毒 (HIV) 的抗病毒药物的临床验证目标。近年来，我们的研究组一直从事这种酶的结构功能研究和一些三维药效团模型的开发，从而鉴定了一系列有效的HIV-1整合酶链转移抑制剂。 INSTIs) 带有吲哚核。为了更好地了解构效关系 (SAR)，我们在此报告了一系列新型 1-H-苄基吲哚衍生物的设计和微波辅助合成。

  DOI：

  10.3390/molecules16086858

文献信息

• 4-[1-(4-Fluorobenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid as a prototype to develop dual inhibitors of HIV-1 integration process
  作者：Laura De Luca、Rosaria Gitto、Frauke Christ、Stefania Ferro、Sara De Grazia、Francesca Morreale、Zeger Debyser、Alba Chimirri

  DOI：10.1016/j.antiviral.2011.07.005

  日期：2011.10

  In recent years several potent HIV-1 integrase (IN) inhibitors have been identified and after the successful clinical use of raltegravir, they have gained a definitive place in the treatment of HIV-1 infection. Yet, there is a continuous effort to design newer inhibitors that target different steps in the integration process. Furthermore, the increased understanding of IN structural biology has opened novel approaches to inhibit IN, such as targeting its multimerization or interaction with cellular cofactors. On these bases, we have concentrated our research on the identification of small molecules able to inhibit two different stages of the integration process: the IN strand-transfer phase and the IN-LEDGF/p75 interaction. We found that the 4-[1-(4-fluorobenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (CHI-1043) is an interesting anti-HIV agent exhibiting dual inhibitory effects. This work has suggested the possibility of also constructing an integration dual inhibitor using a design-in strategy. (C) 2011 Elsevier B.V. All rights reserved.