2-{3-[3-(3-aminopropyl)aminopropyl]aminopropyl}aminomethylquinolin-8-ol | 1395492-19-9

• 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: 2-{3-[3-(3-aminopropyl)aminopropyl]aminopropyl}aminomethylquinolin-8-ol
• 英文别名: 8-Quinolinol, 2-[[[3-[[3-[(3-aminopropyl)amino]propyl]amino]propyl]amino]methyl]-；2-[[3-[3-(3-aminopropylamino)propylamino]propylamino]methyl]quinolin-8-ol
• CAS: 1395492-19-9
• 化学式: C₁₉H₃₁N₅O
• 分子量: 345.488
• InChiKey: NVKIVNKRAVXXLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  95.2
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 盐酸 、 ammonium hydroxide 、 氢气 、 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 水 、 1,2-二氯乙烷 为溶剂， 20.0 ℃ 、2.03 MPa 条件下， 反应 32.0h， 生成 2-{3-[3-(3-aminopropyl)aminopropyl]aminopropyl}aminomethylquinolin-8-ol
  参考文献：
  名称：

  Polyaminoquinoline Iron Chelators for Vectorization of Antiproliferative Agents: Design, Synthesis, and Validation

  摘要：

  Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 mu M. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

  DOI：

  10.1021/bc300324c

文献信息

• METAL-CHELATING COMPOUNDS HAVING AT LEAST ONE POLYAMINO CHAIN
  申请人：UNIVERSITE DE RENNES I

  公开号：US20140364454A1

  公开（公告）日：2014-12-11

  The invention relates to metal-chelating compounds comprising one or more 8-hydroxyquinoline units substituted in position 2 with a nitrogenous group comprising a polyamino chain, wherein the polyamino chain is N-substituted on said nitrogenous group, to the composition containing same, and to the uses thereof in the therapeutic field and in particular in the treatment of diseases associated with an abnormality in the regulation of metal metabolism resulting in a metal overload in human or animal cells.

  该发明涉及含有一个或多个8-羟基喹啉单元的金属螯合化合物，该单元在位置2上被一种氮杂基取代，该氮杂基包括一个聚氨基链，在所述氮杂基上N-取代的聚氨基链，以及含有该化合物的组合物，以及在治疗领域中的用途，特别是在治疗与金属代谢调节异常导致人类或动物细胞中金属超载相关的疾病的用途。
• [EN] METAL-CHELATING COMPOUNDS HAVING AT LEAST ONE POLYAMINO CHAIN<br/>[FR] COMPOSÉS CHÉLATEURS DE MÉTAL PRÉSENTANT AU MOINS UNE CHAÎNE POLYAMINÉE
  申请人：UNIV RENNES

  公开号：WO2013092556A1

  公开（公告）日：2013-06-27

  L'invention concerne des composés chélateurs de métaux comprenant un ou plusieurs motif(s) 8-hydroxyquinoléique(s) substitué(s) en position 2 par un groupe azoté comportant une chaîne polyaminée, la chaîne polyaminée étant N-substituée sur ledit groupe azoté, la composition le contenant, leurs applications dans le domaine thérapeutique et notamment dans le traitement des maladies liées à une anomalie dans la régulation du métabolisme des métaux conduisant à une surcharge en métal dans les cellules humaines ou animales.
• Polyaminoquinoline Iron Chelators for Vectorization of Antiproliferative Agents: Design, Synthesis, and Validation
  作者：Vincent Corcé、Emmanuelle Morin、Solène Guihéneuf、Eric Renault、Stéphanie Renaud、Isabelle Cannie、Raphaël Tripier、Luís M. P. Lima、Karine Julienne、Sébastien G. Gouin、Olivier Loréal、David Deniaud、François Gaboriau

  DOI：10.1021/bc300324c

  日期：2012.9.19

  Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 mu M. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.