N-(7-chloroquinolin-4-yl)propane-1,2-diamine | 191337-12-9

• 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: N-(7-chloroquinolin-4-yl)propane-1,2-diamine
• 英文别名: N-(2-aminopropyl)-7-chloroquinolin-4-amine；7-chloro-4-(1,2-diaminopropyl)quinoline；1-N-(7-chloroquinolin-4-yl)propane-1,2-diamine
• CAS: 191337-12-9
• 化学式: C₁₂H₁₄ClN₃
• 分子量: 235.716
• InChiKey: FEJZETLMLAFGIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二茂铁甲醛 、 N-(7-chloroquinolin-4-yl)propane-1,2-diamine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以84%的产率得到N-(7-chloro-4-quinolyl)-N′-ferrocenyl-propane-1,2-diamine
  参考文献：
  名称：

  Structural Characteristics of Chloroquine-Bridged Ferrocenophane Analogues of Ferroquine May Obviate Malaria Drug-Resistance Mechanisms

  摘要：

  Five compounds displaying an unprecedented binding mode of chloroquine to ferrocene through the bridging of the cyclopentadienyl rings were studied alongside their monosubstituted ferrocene analogues and organic fragments. The antiplasmodial activity was evaluated against strains of the malaria parasite (Plasmodium falciparum). While the chloroquine-bridged ferrocenyl derivatives were less active than their five monosubstituted ferrocenyl analogues, they retained activity in the drug-resistant strains. The biological and physical properties were correlated to antiplasmodial activity. Intramolecular hydrogen bonding was associated with increased antiplasmodial action, but it is not the determining factor. Instead, balance between lipophilicity and hydrophilicity had a greater influence. It was found that calculated partition coefficient (log P) values of 4.5-5.0 and topological polar surfaces area (tPSA) values of similar to 26.0 angstrom(2) give the best balance. The particular conformation, compact size, and lipophilicity/hydrophilicity balance observed in the bridged compounds provide them with the structural characteristics needed to escape the mechanisms responsible for resistance.

  DOI：

  10.1021/jm301422h
• 作为产物：
  描述：

  4,7-二氯喹啉 、 1,2-丙二胺 反应 5.0h， 以60.1%的产率得到N-(7-chloroquinolin-4-yl)propane-1,2-diamine
  参考文献：
  名称：

  新型喹啉-尿素-苯并噻唑杂化物作为有前途的抗结核药物：合成、体外抗结核活性、细胞毒性研究和计算机 ADME 分析

  摘要：

  通过以酰胺化偶联反应为关键步骤的三步合成顺序，成功合成了一系列 25 种新的苯并噻唑-脲-喹啉杂化化合物。合成化合物的结构通过常规光谱工具（ 1 H和13 C NMR和IR）和质谱（HRMS）确认。对这些杂化化合物对结核分枝杆菌H 37 Rv pMSp12::GPF 生物报告菌株的抗结核抑制活性进行了体外评价。在 25 种测试的化合物中，有 17 种表现出有希望的抗结核活性，其低于 62.5 µM (MIC 90 )。具体而言，13 种化合物（6b、6g、6i – j、6l、6o – p、6r – t和6x – y ) 显示出有前途的活性，MIC 90值在 1–10 µM 范围内，而化合物6u是最活跃的，表现出亚微摩尔活性 ( 0.968 µM) 在 CAS 分析中。此外，在 17 种化合物中的 11 种化合物中，在其各自的 MIC 90浓度下，观察到对 HepG2 细胞系的细胞毒性最小（细胞活力高于

  DOI：

  10.3390/ph15050576

文献信息

• N'Da, David D.; Breytenbach, Jaco C., South African Journal of Chemistry, 2011, vol. 64, p. 163 - 172
  作者：N'Da, David D.、Breytenbach, Jaco C.

  DOI：——

  日期：——
• 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.
• Synthesis, in vitro antimalarial and cytotoxicity of artemisinin-aminoquinoline hybrids
  作者：Marli C. Lombard、David D. N’Da、Jaco C. Breytenbach、Peter J. Smith、Carmen A. Lategan

  DOI：10.1016/j.bmcl.2011.01.103

  日期：2011.3

  Dihydroartemisinin (DHA) was coupled to different aminoquinoline moieties forming hybrids 9-14, which were then treated with oxalic acid to form oxalate salts (9a-14a). Compounds 9a, 10a, 12, 12a, and 14a showed comparable potency in vitro to that of chloroquine (CQ) against the chloroquine sensitive (CQS) strain, and were found to be more potent against the chloroquine resistant CQR strain. Hybrids 12 and its oxalate salt 12a were the most active against CQR strain, being 9- and 7-fold more active than CQ, respectively (17.12 nM; 20.76 nM vs 157.9 nM). An optimum chain length was identified having 2 or 3 Cs with or without an extra methylene substituent. (C) 2011 Elsevier Ltd. All rights reserved.
• Structural Characteristics of Chloroquine-Bridged Ferrocenophane Analogues of Ferroquine May Obviate Malaria Drug-Resistance Mechanisms
  作者：Paloma F. Salas、Christoph Herrmann、Jacqueline F. Cawthray、Corinna Nimphius、Alexander Kenkel、Jessie Chen、Carmen de Kock、Peter J. Smith、Brian O. Patrick、Michael J. Adam、Chris Orvig

  DOI：10.1021/jm301422h

  日期：2013.2.28

  Five compounds displaying an unprecedented binding mode of chloroquine to ferrocene through the bridging of the cyclopentadienyl rings were studied alongside their monosubstituted ferrocene analogues and organic fragments. The antiplasmodial activity was evaluated against strains of the malaria parasite (Plasmodium falciparum). While the chloroquine-bridged ferrocenyl derivatives were less active than their five monosubstituted ferrocenyl analogues, they retained activity in the drug-resistant strains. The biological and physical properties were correlated to antiplasmodial activity. Intramolecular hydrogen bonding was associated with increased antiplasmodial action, but it is not the determining factor. Instead, balance between lipophilicity and hydrophilicity had a greater influence. It was found that calculated partition coefficient (log P) values of 4.5-5.0 and topological polar surfaces area (tPSA) values of similar to 26.0 angstrom(2) give the best balance. The particular conformation, compact size, and lipophilicity/hydrophilicity balance observed in the bridged compounds provide them with the structural characteristics needed to escape the mechanisms responsible for resistance.
• New Quinoline–Urea–Benzothiazole Hybrids as Promising Antitubercular Agents: Synthesis, In Vitro Antitubercular Activity, Cytotoxicity Studies, and In Silico ADME Profiling
  作者：Rashmika Moodley、Chakes Mashaba、Goitsemodimo Rakodi、Nomagugu Ncube、Mabuatsela Maphoru、Mohammed Balogun、Audrey Jordan、Digby Warner、Rene Khan、Matshawandile Tukulula

  DOI：10.3390/ph15050576

  日期：——

  inhibitory activity against the Mycobacterium tuberculosis H37Rv pMSp12::GPF bioreporter strain was undertaken. Of the 25 tested compounds, 17 exhibited promising anti-TB activities of less than 62.5 µM (MIC90). Specifically, 13 compounds (6b, 6g, 6i–j, 6l, 6o–p, 6r–t, and 6x–y) showed promising activity with MIC90 values in the range of 1–10 µM, while compound 6u, being the most active, exhibited sub-micromolar

  通过以酰胺化偶联反应为关键步骤的三步合成顺序，成功合成了一系列 25 种新的苯并噻唑-脲-喹啉杂化化合物。合成化合物的结构通过常规光谱工具（ 1 H和13 C NMR和IR）和质谱（HRMS）确认。对这些杂化化合物对结核分枝杆菌H 37 Rv pMSp12::GPF 生物报告菌株的抗结核抑制活性进行了体外评价。在 25 种测试的化合物中，有 17 种表现出有希望的抗结核活性，其低于 62.5 µM (MIC 90 )。具体而言，13 种化合物（6b、6g、6i – j、6l、6o – p、6r – t和6x – y ) 显示出有前途的活性，MIC 90值在 1–10 µM 范围内，而化合物6u是最活跃的，表现出亚微摩尔活性 ( 0.968 µM) 在 CAS 分析中。此外，在 17 种化合物中的 11 种化合物中，在其各自的 MIC 90浓度下，观察到对 HepG2 细胞系的细胞毒性最小（细胞活力高于