5,5'-(4-nitrobenzylazanediyl)bis(methylene)diquinolin-8-ol | 1146365-13-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5,5'-(4-nitrobenzylazanediyl)bis(methylene)diquinolin-8-ol
• 英文别名: 5-[[(8-Hydroxyquinolin-5-yl)methyl-[(4-nitrophenyl)methyl]amino]methyl]quinolin-8-ol
• CAS: 1146365-13-0
• 化学式: C₂₇H₂₂N₄O₄
• 分子量: 466.496
• InChiKey: QUUAYKCXQOVFME-UHFFFAOYSA-N

物化性质

• 沸点：
  721.3±55.0 °C(predicted)
• 密度：
  1.410±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-硝基苄胺 、 5-(氯甲基)-8-羟基喹啉盐酸盐 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以56%的产率得到5,5'-(4-nitrobenzylazanediyl)bis(methylene)diquinolin-8-ol
  参考文献：
  名称：

  Discovery of a new family of bis-8-hydroxyquinoline substituted benzylamines with pro-apoptotic activity in cancer cells: Synthesis, structure–activity relationship, and action mechanism studies

  摘要：

  Bis-8-hydroxyquinoline substituted benzylamines have been synthesized and screened for their antitumor activity on KB3 cell line model. Synthesis of this series of new analogues was accomplished using a one pot specific methodology which allows the synthesis of both bis- and mono-8-hydroxyquinoline substituted benzylamines. Among the synthesized compounds two compounds (4a and 5a), respectively, named JLK 1472 and JLK 1486, were particularly potent on KB3 cell line. Their CC50 values being, respectively, 2.6 and 1.3 nM. Screened on a panel of cell lines showing various phenotype alterations, both compounds were found inactive on some cell lines such as PC3 (prostate cell line) and SF268 (neuroblastoma cell line) while highly active on other different cell lines. Mechanistic studies reveal that these two analogues did not affect tubulin and microtubules neither they exert a proteasomal inhibition effect. In contrast 4a and 5a activate specifically caspase 3/7 and not caspase 8 and 9, suggesting that their biological target should he located upstream from caspase 3/7. Moreover their cytotoxic effect is potentiated by the pro-apoptotic effects of TRAIL. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.03.042

文献信息

• Discovery of a new family of bis-8-hydroxyquinoline substituted benzylamines with pro-apoptotic activity in cancer cells: Synthesis, structure–activity relationship, and action mechanism studies
  作者：Vincent Moret、Younes Laras、Thierry Cresteil、Geneviève Aubert、Dou Q. Ping、Chen Di、Magali Barthélémy-Requin、Christophe Béclin、Vincent Peyrot、Diane Allegro、Amandine Rolland、Francesca De Angelis、Evelina Gatti、Philippe Pierre、Luca Pasquini、Eleonora Petrucci、Ugo Testa、Jean-Louis Kraus

  DOI：10.1016/j.ejmech.2008.03.042

  日期：2009.2

  Bis-8-hydroxyquinoline substituted benzylamines have been synthesized and screened for their antitumor activity on KB3 cell line model. Synthesis of this series of new analogues was accomplished using a one pot specific methodology which allows the synthesis of both bis- and mono-8-hydroxyquinoline substituted benzylamines. Among the synthesized compounds two compounds (4a and 5a), respectively, named JLK 1472 and JLK 1486, were particularly potent on KB3 cell line. Their CC50 values being, respectively, 2.6 and 1.3 nM. Screened on a panel of cell lines showing various phenotype alterations, both compounds were found inactive on some cell lines such as PC3 (prostate cell line) and SF268 (neuroblastoma cell line) while highly active on other different cell lines. Mechanistic studies reveal that these two analogues did not affect tubulin and microtubules neither they exert a proteasomal inhibition effect. In contrast 4a and 5a activate specifically caspase 3/7 and not caspase 8 and 9, suggesting that their biological target should he located upstream from caspase 3/7. Moreover their cytotoxic effect is potentiated by the pro-apoptotic effects of TRAIL. (C) 2008 Elsevier Masson SAS. All rights reserved.