N,N′-dibenzyl-2-{2-[(2,4-dinitrophenyl)thio]-1H-indol-3-yl}ethanamine

• 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: N,N′-dibenzyl-2-{2-[(2,4-dinitrophenyl)thio]-1H-indol-3-yl}ethanamine
• 英文别名: N,N-dibenzyl-2-[2-(2,4-dinitrophenyl)sulfanyl-1H-indol-3-yl]ethanamine
• 化学式: C₃₀H₂₆N₄O₄S
• 分子量: 538.627
• InChiKey: RXMZNQNBGYJMJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  色胺 在 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N,N′-dibenzyl-2-{2-[(2,4-dinitrophenyl)thio]-1H-indol-3-yl}ethanamine
  参考文献：
  名称：

  Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity

  摘要：

  TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N,N'-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC50 0.2 +/- 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an lcilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1 - 1 mu g s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the SI-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.

  DOI：

  10.1021/acs.jmedchem.8b00545

文献信息

• Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity
  作者：Alessia Bertamino、Nunzio Iraci、Carmine Ostacolo、Paolo Ambrosino、Simona Musella、Veronica Di Sarno、Tania Ciaglia、Giacomo Pepe、Marina Sala、Maria Virginia Soldovieri、Ilaria Mosca、Sara Gonzalez-Rodriguez、Asia Fernandez-Carvajal、Antonio Ferrer-Montiel、Ettore Novellino、Maurizio Taglialatela、Pietro Campiglia、Isabel Gomez-Monterrey

  DOI：10.1021/acs.jmedchem.8b00545

  日期：2018.7.26

  TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N,N'-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC50 0.2 +/- 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an lcilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1 - 1 mu g s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the SI-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.