(3-aminopropyl)({3-[(7-chloroquinolin-4-yl)amino]propyl})methylamine | 947699-89-0

• 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: (3-aminopropyl)({3-[(7-chloroquinolin-4-yl)amino]propyl})methylamine
• 英文别名: N¹-(3-aminopropyl)-N³-(7-chloroquinolin-4-yl)-N¹-methylpropane-1,3-diamine；N'-[3-[(7-chloroquinolin-4-yl)amino]propyl]-N'-methylpropane-1,3-diamine
• CAS: 947699-89-0
• 化学式: C₁₆H₂₃ClN₄
• 分子量: 306.838
• InChiKey: ZPOLLAFDENPHSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  54.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氯喹啉 、 (3-aminopropyl)({3-[(7-chloroquinolin-4-yl)amino]propyl})methylamine 在 碳酸氢钠 作用下， 以 neat (no solvent) 为溶剂， 反应 24.0h， 以31%的产率得到N-(7-chloroquinolin-4-yl)-N'-methyl-N'-[3-(quinolin-2-ylamino)propyl]propane-1,3-diamine
  参考文献：
  名称：

  Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme

  摘要：

  Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two pi-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a and 12a showed potent antimalarial activities compared to artesunate, as well as a prolonged duration of antimalarial effect. We found a good correlation between protective activity against hemin degradation and antimalarial activity. Compounds 8b and 3a strongly inhibited hemozoin formation catalyzed by heme detoxification protein.

  DOI：

  10.1021/acsmedchemlett.8b00222
• 作为产物：
  描述：

  4,7-二氯喹啉 、 N,N-双(3-氨丙基)甲胺 以67%的产率得到(3-aminopropyl)({3-[(7-chloroquinolin-4-yl)amino]propyl})methylamine
  参考文献：
  名称：

  Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides

  摘要：

  A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1'-carbonyldiimidazole as coupling agent. These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum. Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined. All compounds were found active, with IC50 values ranging between 0.04-0.5 mu M and 0.07-1.8 mu M against 3D7 and W2, respectively. They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells. However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested. It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI = 435) towards the parasitic cells. During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.032

文献信息

• [EN] MOLECULES THAT BIND TO TDP-43 FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS AND RELATED DISORDERS<br/>[FR] MOLÉCULES QUI SE LIENT À TDP-43 POUR LE TRAITEMENT DE LA SCLÉROSE LATÉRALE AMYOTROPHIQUE ET DE TROUBLES APPARENTÉS
  申请人：BIOHAVEN THERAPEUTICS LTD

  公开号：WO2021035101A4

  公开（公告）日：2021-04-15
• Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides
  作者：Frans J. Smit、David D. N’Da

  DOI：10.1016/j.bmc.2013.12.032

  日期：2014.2

  A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1'-carbonyldiimidazole as coupling agent. These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum. Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined. All compounds were found active, with IC50 values ranging between 0.04-0.5 mu M and 0.07-1.8 mu M against 3D7 and W2, respectively. They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells. However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested. It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI = 435) towards the parasitic cells. During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs. (C) 2013 Elsevier Ltd. All rights reserved.
• COMPOUND WITH ANTIMALARIAL ACTIVITY AND ANTIMALARIAL DRUG CONTAINING THE SAME AS ACTIVE INGREDIENT
  申请人：Nagoya City University

  公开号：EP2006287B1

  公开（公告）日：2011-08-31
• MOLECULES THAT BIND TO TDP-43 FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS AND RELATED DISORDERS
  申请人：Biohaven Therapeutics Ltd.

  公开号：US20220388962A1

  公开（公告）日：2022-12-08

  Pharmaceutical compositions of the invention comprise TDP-43 binding agents having a disease-modifying action in the treatment of diseases associated with TDP-43 that include ALS, FTLD, CTE, hippocampal sclerosis of aging (CARTS), Alzheimer's disease, and Alzheimer's disease related disorder, and disease that involve excess amounts of TDP-43 in the cytosol.
• Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme
  作者：Yosuke Sakata、Kosuke Yabunaka、Yuko Kobayashi、Hirohisa Omiya、Naoki Umezawa、Hye-Sook Kim、Yusuke Wataya、Yoshimi Tomita、Yosuke Hisamatsu、Nobuki Kato、Hirokazu Yagi、Tadashi Satoh、Koichi Kato、Haruto Ishikawa、Tsunehiko Higuchi

  DOI：10.1021/acsmedchemlett.8b00222

  日期：2018.10.11

  Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two pi-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a and 12a showed potent antimalarial activities compared to artesunate, as well as a prolonged duration of antimalarial effect. We found a good correlation between protective activity against hemin degradation and antimalarial activity. Compounds 8b and 3a strongly inhibited hemozoin formation catalyzed by heme detoxification protein.