5-chloro-1-(4-chlorobenzyl)-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-1H-indole-2-carboxamide

• 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: 5-chloro-1-(4-chlorobenzyl)-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-1H-indole-2-carboxamide
• 英文别名: 5-chloro-1-[(4-chlorophenyl)methyl]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]indole-2-carboxamide
• 化学式: C₂₇H₂₃Cl₂N₃O₂
• 分子量: 492.405
• InChiKey: FKVPDGSMPQLFKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  59
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-氯吲哚-2-羧酸甲酯 在 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.5h， 生成 5-chloro-1-(4-chlorobenzyl)-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  Design, synthesis, biological evaluation and docking study of novel indole-2-amide as anti-inflammatory agents with dual inhibition of COX and 5-LOX

  摘要：

  In this work, a series of novel indole-2-amide compounds were designed, synthesized, characterized and the anti-inflammatory activity in vivo were evaluated. Compounds 8a, 10b, 12h, and 121 exhibited marked anti-inflammatory activity in 2,4-Dinitrofluorobenzenethe (DNFB) - induced mice auricle edema model. Further, compounds 8a, 10b and 12h exhibited potential in vitro COX-2 inhibitory activity (IC50 = 21.86, 233 and 23.21 nM, respectively), while the reference drug celecoxib was 11.20 nM. The most promising compound 10b was exhibited the highest selectivity for COX-2 (selectivity index (COX-1/COX-2) = 17.45) and moderate 5-LOX inhibitory activity (IC50 = 66 nM), which comparable to positive controlled zileuton (IC50 = 38.91 nM). In addition, the test results showed compounds 10b and 12h no significant cytotoxic activity on normal cells (RAW264.7). Further, at the active sites of the COX-1, COX-2 co crystals, 3b and 41 showed higher binding forces in the molecular docking study, which consistent with the results of in vitro experiments. These results demonstrated that these compounds had dual inhibitory activity of COX/5-LOX, providing clues for further searching for safer and more effective anti-inflammatory drugs. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.07.004

文献信息

• Design, synthesis, biological evaluation and docking study of novel indole-2-amide as anti-inflammatory agents with dual inhibition of COX and 5-LOX
  作者：Yuanzheng Huang、Bin Zhang、Jiaming Li、Huicai Liu、Yanchun Zhang、Zhang Yang、Wandong Liu

  DOI：10.1016/j.ejmech.2019.07.004

  日期：2019.10

  In this work, a series of novel indole-2-amide compounds were designed, synthesized, characterized and the anti-inflammatory activity in vivo were evaluated. Compounds 8a, 10b, 12h, and 121 exhibited marked anti-inflammatory activity in 2,4-Dinitrofluorobenzenethe (DNFB) - induced mice auricle edema model. Further, compounds 8a, 10b and 12h exhibited potential in vitro COX-2 inhibitory activity (IC50 = 21.86, 233 and 23.21 nM, respectively), while the reference drug celecoxib was 11.20 nM. The most promising compound 10b was exhibited the highest selectivity for COX-2 (selectivity index (COX-1/COX-2) = 17.45) and moderate 5-LOX inhibitory activity (IC50 = 66 nM), which comparable to positive controlled zileuton (IC50 = 38.91 nM). In addition, the test results showed compounds 10b and 12h no significant cytotoxic activity on normal cells (RAW264.7). Further, at the active sites of the COX-1, COX-2 co crystals, 3b and 41 showed higher binding forces in the molecular docking study, which consistent with the results of in vitro experiments. These results demonstrated that these compounds had dual inhibitory activity of COX/5-LOX, providing clues for further searching for safer and more effective anti-inflammatory drugs. (C) 2019 Published by Elsevier Masson SAS.