N-{3-[4-(3-aminopropyl)piperazin-1-yl]propyl}-7-chloroquinolin-4-amine | 497233-85-9

• 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: N-{3-[4-(3-aminopropyl)piperazin-1-yl]propyl}-7-chloroquinolin-4-amine
• 英文别名: N-[3-[4-(3-aminopropyl)piperazin-1-yl]propyl]-7-chloroquinolin-4-amine
• CAS: 497233-85-9
• 化学式: C₁₉H₂₈ClN₅
• 分子量: 361.918
• InChiKey: QOMHZEDGTJFHRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  57.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{3-[4-(3-aminopropyl)piperazin-1-yl]propyl}-7-chloroquinolin-4-amine 在 3 A molecular sieve 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-[3-[4-[3-[(7-chloroquinolin-4-yl)amino]propyl]piperazin-1-yl]propyl]-N-(cyclopropylmethyl)naphthalene-2-carboxamide
  参考文献：
  名称：

  Similar Structure−Activity Relationships of Quinoline Derivatives for Antiprion and Antimalarial Effects

  摘要：

  Prion diseases are invariably fatal neurodegenerative diseases, in which the infectious agent consists of PrPSc, a pathogenic misfolded isoform of the normal cellular prion protein ( PrPC). Until now, no pharmacological options exist for these novel pathogens. Here we describe the screening of a series of polyquinolines and quinolines linked to a large variety of terminal groups for their ability to cure a persistently prion infected cell line (ScN2a). Several compounds showed antiprion activity in the nanomolar range. The most active molecule, named 42, had a half-effective concentration (EC50) for antiprion activity of 50 nM. In a library of quinoline derivatives we were able to identify several structure-activity relationships (SAR). Remarkably, antiprion SAR in ScN2a cells were similar to antimalarial SAR in a cell model of malaria, particularly for the sulfonamide quinoline derivatives, suggesting that some molecular targets of antiprion and antimalarial substances overlap.

  DOI：

  10.1021/jm0602763
• 作为产物：
  描述：

  1,4-双(3-氨基丙基)哌嗪 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-{3-[4-(3-aminopropyl)piperazin-1-yl]propyl}-7-chloroquinolin-4-amine
  参考文献：
  名称：

  Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice

  摘要：

  In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50 < 1 mu M against promastigote stages of L. infantum and L. tropica, and five compounds showed IC50 < 1 mu M against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.

  DOI：

  10.1021/acsmedchemlett.8b00053

文献信息

• Parallel Synthesis and Anti-Malarial Activity of a Sulfonamide Library
  作者：A Ryckebusch、R Déprez-Poulain、M.-A Debreu-Fontaine、R Vandaele、E Mouray、P Grellier、C Sergheraert

  DOI：10.1016/s0960-894x(02)00475-4

  日期：2002.9

  Solution-phase synthesis and evaluation of a library of 31 sulfonamides as inhibitors of a chloroquine-resistant strain of Plasmodium falciparum are described. The most potent compound displayed an activity 100-fold better than chloroquine. Experiments using a fluorescent sulfonamide derivative suggest that their site of action inside the parasite is different to that of chloroquine.

  描述了溶液相合成和31种磺胺类药物文库的评估，这些文库是恶性疟原虫抗氯喹菌株的抑制剂。最有效的化合物显示出的活性比氯喹好100倍。使用荧光磺酰胺衍生物的实验表明，它们在寄生虫内的作用部位与氯喹的作用部位不同。
• Use of 1,4-bis (3-aminoalkyl) piperazine derivatives in the treatment of neurodegenerative diseases
  申请人：Sergeant Nicolas

  公开号：US20090149464A1

  公开（公告）日：2009-06-11

  Use of 1,4-bis(3-aminoalkyl)piperazine derivatives as defined in formula I or II for the manufacture of a pharmaceutical composition intended for the treatment of neurodegenerative diseases, related neurodegenerative diseases, developmental diseases or cancer. The instant invention is also directed to some specific 1,4-bis(3-aminoalkyl)piperazine derivatives and pharmaceutical composition including them.

  使用公式I或II中定义的1,4-双(3-氨基烷基)哌嗪衍生物制造用于治疗神经退行性疾病、相关神经退行性疾病、发育性疾病或癌症的药物组合物。本发明还涉及一些特定的1,4-双(3-氨基烷基)哌嗪衍生物和包括它们的药物组合物。
• WO2006/51489
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and antiplasmodial activity of new N-[3-(4-{3-[(7-chloroquinolin-4-yl)amino]propyl}piperazin-1-yl)propyl]carboxamides
  作者：Marcus Freitag、Marcel Kaiser、Tim Larsen、Vida Zohrabi-Kalantari、Philipp Heidler、Andreas Link

  DOI：10.1016/j.bmc.2006.12.034

  日期：2007.4

  The parallel acylation of N-3-[4-(3-aminopropyl)piperazin-1-yl]propyl}-7-chloroquinolin-4-amine with polymer-bound carboxylic acids opened straightforward access to novel aminoquinolines with activity against Plasmodium falciparum strains in vitro. Using this amino scaffold prepared in solution and polymer-bound carboxylic, we have synthesized a series of 29 new compounds in good to excellent yield and purity. Biological evaluation included determination of the activity against a chloroquine (CQ) sensitive strain and a CQ resistant mutant. Most of the novel structures presented here displayed activity against both strains in the lower nanomolar range, four compounds showed an at least fourfold increase in the ratio of inhibition of CQ resistant to sensitive strains over CQ itself. These results suggest that this derivatization technique is a useful method to speed up structure-activity relationship studies on aminoquinolines toward improved activity versus CQ resistant strains of P. falciparum in vitro. (c) 2006 Elsevier Ltd. All rights reserved.
• Design, synthesis and antimalarial activity of novel, quinoline-Based, zinc metallo-aminopeptidase inhibitors
  作者：Marian Flipo、Isabelle Florent、Philippe Grellier、Christian Sergheraert、Rebecca Deprez-Poulain

  DOI：10.1016/s0960-894x(03)00550-x

  日期：2003.8

  PfA-M1, a neutral zinc aminopeptidase of Plasmodium falciparum, is a new potential target for the discovery of anti-malarials. The design and synthesis of a library of 45 quinoline-based inhibitors of PfA-M1 is reported. The best inhibitor displays an IC50 of 854 nM. The antimalarial activity on a CQ-resistant strain and the specificity towards mammalian aminopeptidase N are also discussed. (C) 2003 Elsevier Ltd. All rights reserved.