ethyl 2-((3,4-dichlorophenylthio)methyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate

• 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 2-((3,4-dichlorophenylthio)methyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate
• 英文别名: ethyl 2-[(3,4-dichlorophenyl)sulfanylmethyl]-5-hydroxy-1H-benzo[g]indole-3-carboxylate
• 化学式: C₂₂H₁₇Cl₂NO₃S
• 分子量: 446.354
• InChiKey: DLSRBMSLUCPHHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  87.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二氯苯硫酚 在 ammonium acetate 、 溶剂黄146 、 三乙胺 、 zinc(II) iodide 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 6.5h， 生成 ethyl 2-((3,4-dichlorophenylthio)methyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate
  参考文献：
  名称：

  Exploring the role of chloro and methyl substitutions in 2-phenylthiomethyl-benzoindole derivatives for 5-LOX enzyme inhibition

  摘要：

  Following the results we previously reported on a series of ethyl 2-phenylthiomethyl 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase (5-LOX) inhibitors, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand.The first level of structural modification involved the annelation of benzene to the indole, yielding corresponding benzo[g]indole derivatives, systematic optimization of methyl or chlorine groups in meta, ortho- and ortho/para-position of 2-phenylthiomethyl moiety were applied. The reported results show that extension of the aromatic core led to a great enhancement of activity, especially in cell-free assay, and the accurate structure-based design provided compounds 6f, 6g and 61 that block 5-LOX activity in cell-free assays with IC50 ranging from 0.17 to 0.22 mu M, and suppress 5-LOX product synthesis in polymorphonuclear leukocytes with IC50 ranging from 0.19 to 0.37 mu M. Moreover we have identified 6f and 61 as dual 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1) inhibitors and compound 61 significantly reduces inflammatory reactions in the carrageenan-induced mouse paw oedema. The reported in vivo analysis, together with the accessible synthetic procedure, stimulate for the generation of further potent antinflammatory benzoindoles-based agents. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.11.048

文献信息

• Exploring the role of chloro and methyl substitutions in 2-phenylthiomethyl-benzoindole derivatives for 5-LOX enzyme inhibition
  作者：Antonella Peduto、Verena Krauth、Selene Collarile、Fiederike Dehm、Marika Ambruosi、Carmela Belardo、Francesca Guida、Antonio Massa、Veronica Esposito、Sabatino Maione、Mario de Rosa、Oliver Werz、Rosanna Filosa

  DOI：10.1016/j.ejmech.2015.11.048

  日期：2016.1

  Following the results we previously reported on a series of ethyl 2-phenylthiomethyl 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase (5-LOX) inhibitors, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand.The first level of structural modification involved the annelation of benzene to the indole, yielding corresponding benzo[g]indole derivatives, systematic optimization of methyl or chlorine groups in meta, ortho- and ortho/para-position of 2-phenylthiomethyl moiety were applied. The reported results show that extension of the aromatic core led to a great enhancement of activity, especially in cell-free assay, and the accurate structure-based design provided compounds 6f, 6g and 61 that block 5-LOX activity in cell-free assays with IC50 ranging from 0.17 to 0.22 mu M, and suppress 5-LOX product synthesis in polymorphonuclear leukocytes with IC50 ranging from 0.19 to 0.37 mu M. Moreover we have identified 6f and 61 as dual 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1) inhibitors and compound 61 significantly reduces inflammatory reactions in the carrageenan-induced mouse paw oedema. The reported in vivo analysis, together with the accessible synthetic procedure, stimulate for the generation of further potent antinflammatory benzoindoles-based agents. (C) 2015 Published by Elsevier Masson SAS.