1-[1-(2-methoxyethanesulfonyl)-4-[4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl]-4-methylpiperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-[1-(2-methoxyethanesulfonyl)-4-[4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl]-4-methylpiperazine
• 英文别名: 1-(2-Methoxyethylsulfonyl)-6-(4-methylpiperazin-1-yl)-4-[4-(trifluoromethyl)phenyl]pyrrolo[2,3-b]pyridine；1-(2-methoxyethylsulfonyl)-6-(4-methylpiperazin-1-yl)-4-[4-(trifluoromethyl)phenyl]pyrrolo[2,3-b]pyridine
• 化学式: C₂₂H₂₅F₃N₄O₃S
• 分子量: 482.527
• InChiKey: SSZMVCXZZWIPDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  76
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-氯-7-氮杂吲哚 在 palladium diacetate 、 sodium hydride 、 硫酸二甲酯 作用下， 以 正庚烷 、 乙酸丁酯 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 169.5h， 生成 1-[1-(2-methoxyethanesulfonyl)-4-[4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-6-yl]-4-methylpiperazine
  参考文献：
  名称：

  1-Sulfonyl-6-Piperazinyl-7-Azaindoles as potent and pseudo-selective 5-HT 6 receptor antagonists

  摘要：

  A series of 1-Sulfonyl-6-Piperazinyl-7-Azaindoles, showing strong antagonistic activity to 5-HT6 receptor (5-HT6R) was synthesized and characterized. The series was optimized to reduce activity on D-2 receptor. Based on the selectivity against this off-target and the analysis of the ADME-tox profile, compound 1c was selected for in vivo efficacy assessment, which demonstrated procognitive effects as shown in reversal of scopolamine induced amnesia in an elevated plus maze test in mice. Compound 3, the demethylated version of compound 1c, was profiled against a panel of 106 receptors, channels and transporters, indicating only D-3 receptor as a major off-target. Compound 3 has been selected for this study over compound 1c because of the higher 5-HT6R/D2R binding ratio. These results have defined a new direction for the design of our pseudo-selective 5-HT6R antagonists. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.04.024

文献信息

• 1-Sulfonyl-6-Piperazinyl-7-Azaindoles as potent and pseudo-selective 5-HT 6 receptor antagonists
  作者：Charles-Henry Fabritius、Ullamari Pesonen、Josef Messinger、Raymond Horvath、Harri Salo、Michał Gałęzowski、Mariusz Galek、Klaudia Stefańska、Joanna Szeremeta-Spisak、Marta Olszak-Płachta、Anna Buda、Justyna Adamczyk、Marcin Król、Peteris Prusis、Magdalena Sieprawska-Lupa、Maciej Mikulski、Katja Kuokkanen、Hugh Chapman、Radosław Obuchowicz、Timo Korjamo、Niina Jalava、Mateusz Nowak

  DOI：10.1016/j.bmcl.2016.04.024

  日期：2016.6

  A series of 1-Sulfonyl-6-Piperazinyl-7-Azaindoles, showing strong antagonistic activity to 5-HT6 receptor (5-HT6R) was synthesized and characterized. The series was optimized to reduce activity on D-2 receptor. Based on the selectivity against this off-target and the analysis of the ADME-tox profile, compound 1c was selected for in vivo efficacy assessment, which demonstrated procognitive effects as shown in reversal of scopolamine induced amnesia in an elevated plus maze test in mice. Compound 3, the demethylated version of compound 1c, was profiled against a panel of 106 receptors, channels and transporters, indicating only D-3 receptor as a major off-target. Compound 3 has been selected for this study over compound 1c because of the higher 5-HT6R/D2R binding ratio. These results have defined a new direction for the design of our pseudo-selective 5-HT6R antagonists. (C) 2016 Elsevier Ltd. All rights reserved.