JLK 1486 | 1146365-12-9

• 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: JLK 1486
• 英文别名: 5,5'-(4-(trifluoromethyl)benzylazanediyl)bis(methylene)diquinolin-8-ol；Unii-8KG95Q2dqh；5-[[(8-hydroxyquinolin-5-yl)methyl-[[4-(trifluoromethyl)phenyl]methyl]amino]methyl]quinolin-8-ol
• CAS: 1146365-12-9
• 化学式: C₂₈H₂₂F₃N₃O₂
• 分子量: 489.497
• InChiKey: JZARXLRJMQKPON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  69.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  JLK 1486 在 水 、 N,N-二甲基甲酰胺 作用下， 反应 48.0h， 生成 5-((4-(三氟甲基)苄基氨基)甲基)喹啉-8-醇 、 5-Methylidene-4a,8a-dihydroquinolin-8-one
  参考文献：
  名称：

  [EN] PPAR AGONIST COMPOSITIONS AND METHODS OF USE
  [FR] COMPOSITIONS AGONISTES DE PPAR ET PROCÉDÉS D'UTILISATION

  摘要：

  治疗或预防主体的PPAR响应性疾病的方法，包括向主体给予一种PPAR激动剂，该激动剂包括一种8-羟基喹啉-亚甲基-N-基团，其有效剂量能够激活PPAR多肽。

  公开号：

  WO2010073235A1
• 作为产物：
  描述：

  4-(三氟甲基)苄胺 、 5-(氯甲基)-8-羟基喹啉盐酸盐 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 JLK 1486
  参考文献：
  名称：

  双8-羟基喹啉和双8-羟基喹啉N取代的胺：两个杂环之间的单个甲基结构差异，可调节抗增殖作用

  摘要：

  据报道，合成了一系列的双-8-羟基喹啉-和双-8-羟基喹啉取代的N-苄基或硫代苯基胺及其相应的双-8-羟基喹啉。已经评估了两个系列的体外生长抑制作用。已经观察到，来自bis-8-羟基喹啉系列的类似物发挥纳摩尔范围的活性，而发现来自bis-8-羟基奎纳丁系列的相应类似物的抗增殖活性大大降低。分子对接和化学物理性质解释了两个类似物系列之间观察到的生长抑制差异，这些差异仅因杂环的2位上存在甲基而有所不同。J.杂环化​​学。（2010）。

  DOI：

  10.1002/jhet.304

文献信息

• PPAR AGONIST COMPOSITIONS AND METHODS OF USE
  申请人：Kraus Jean-Louis

  公开号：US20110251238A1

  公开（公告）日：2011-10-13

  Method for treating or preventing a PPAR-responsive condition in a subject, comprising administering to the subject a PPAR agonist that comprises a 8-hydroxyquinoline-methylene-N- group in an amount effective to activate a PPAR polypeptide.

  治疗或预防受体PPAR反应性疾病的方法，包括向受体施用含有8-羟基喹啉-亚甲基-N-基团的PPAR激动剂，以有效激活PPAR多肽。
• 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.
• Structure–activity relationships and mechanism of action of antitumor bis 8-hydroxyquinoline substituted benzylamines
  作者：Sébastien Madonna、Christophe Béclin、Younes Laras、Vincent Moret、Aline Marcowycz、Delphine Lamoral-Theys、Jacques Dubois、Magali Barthelemy-Requin、Gaëlle Lenglet、Sabine Depauw、Thierry Cresteil、Geneviève Aubert、Valérie Monnier、Robert Kiss、Marie-Hélène David-Cordonnier、Jean-Louis Kraus

  DOI：10.1016/j.ejmech.2009.11.006

  日期：2010.2

  A series of twenty six 8-hydroxyquinoline substituted amines, structurally related to compounds 2 and 3, were synthesized to evaluate the effects of structural changes on antitumor activity and understand their mechanism of action. The studies were performed on a wide variety of cancer cell lines within glioma and carcinoma models. The results obtained from chemical models and biological techniques such as microarrays suggest the following hypothesis that a quinone methide intermediate which does not react with DNA but which gives covalent protein thiol adducts. Micro-array analysis showed that the drugs induce the expression of a variety of stress related genes responsible for the cytotoxic and cytostatic effects in carcinoma and glioblastoma cells respectively. The described analogues could represent new promising anti-cancer candidates with specific action mechanisms, targeting accessible thiols from specific proteins and inducing potent anti-cancer effects. (C) 2009 Elsevier Masson SAS. All rights reserved.
• [EN] PPAR AGONIST COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSITIONS AGONISTES DE PPAR ET PROCÉDÉS D'UTILISATION
  申请人：BIOPHARMED

  公开号：WO2010073235A1

  公开（公告）日：2010-07-01

  Method for treating or preventing a PPAR-responsive condition in a subject, comprising administering to the subject a PPAR agonist that comprises a 8-hydroxyquinoline-methylene-N- group in an amount effective to activate a PPAR polypeptide.

  治疗或预防主体的PPAR响应性疾病的方法，包括向主体给予一种PPAR激动剂，该激动剂包括一种8-羟基喹啉-亚甲基-N-基团，其有效剂量能够激活PPAR多肽。
• Bis-8-hydroxyquinoline and bis-8-hydroxyquinaldine N-substituted amines: A single methyl group structural difference between the two heterocycles, which modulates the antiproliferative effects
  作者：Sébastien Madonna、Aline Marcowycz、Delphine Lamoral-Theys、Gwendoline Van Goietsenoven、Jean Dessolin、Christine Pirker、Sabine Spiegl-Kreinecker、César-Alain Biraboneye、Walter Berger、Robert Kiss、Jean-Louis Kraus

  DOI：10.1002/jhet.304

  日期：——

  uted N-benzyl or thiophenyl amines and their corresponding bis-8-hydroxyquinoline is reported. In vitro growth inhibitory effects of both series have been evaluated. It has been observed that analogs from the bis-8-hydroxyquinoline series exert nanomolar range activity, whereas the antiproliferative activity of the corresponding analogs from the bis-8-hydroxyquinaldine series was found to be drastically

  据报道，合成了一系列的双-8-羟基喹啉-和双-8-羟基喹啉取代的N-苄基或硫代苯基胺及其相应的双-8-羟基喹啉。已经评估了两个系列的体外生长抑制作用。已经观察到，来自bis-8-羟基喹啉系列的类似物发挥纳摩尔范围的活性，而发现来自bis-8-羟基奎纳丁系列的相应类似物的抗增殖活性大大降低。分子对接和化学物理性质解释了两个类似物系列之间观察到的生长抑制差异，这些差异仅因杂环的2位上存在甲基而有所不同。J.杂环化​​学。（2010）。