N8-(4-amino-1-methylpentyl)-4-ethyl-6-methoxy-5-pentyloxy-8-quinolinamine | 672912-25-3

• 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: N8-(4-amino-1-methylpentyl)-4-ethyl-6-methoxy-5-pentyloxy-8-quinolinamine
• 英文别名: 4-ethyl-5-(pentyloxy)primaquine；4-ethyl-5-pentyloxyprimaquine；4-N-(4-ethyl-6-methoxy-5-pentoxyquinolin-8-yl)pentane-1,4-diamine
• CAS: 672912-25-3
• 化学式: C₂₂H₃₅N₃O₂
• 分子量: 373.539
• InChiKey: ROYJEBXFKCEWSH-UHFFFAOYSA-N

物化性质

• 沸点：
  540.0±50.0 °C(Predicted)
• 密度：
  1.057±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  69.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N8-(4-amino-1-methylpentyl)-4-ethyl-6-methoxy-5-pentyloxy-8-quinolinamine 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 (2S)-N¹-[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-2-amino-3-methylbutanamide dihydrochloride
  参考文献：
  名称：

  8-Quinolinamines conjugated with amino acids are exhibiting potent blood-schizontocidal antimalarial activities

  摘要：

  Alanine, lysine, ornithine and valine conjugated to primaquine and other 8-quinolinamine antinialarials were prepared for blood-schizontocidal antimalarial activity evaluation. The analogues were examined in vivo against Plasmodium berghei (drug-sensitive strain) and Plasinodium yoelii nigeriensis (highly virulent multi-drug-resistant strain) infected mice models. N-1-[4-(5Butoxy-4-ethyl-6-methoxy-8-quinolylamino)pentyl]-(2S)-2,6-diaminohexanamide (20) which showed curative activity at 5 mg/kg in the P. berghei test emerged as the most effective compound. N-1-[4-(4-Ethyl-5-hexoxy-6-methoxy-8-quinolylamino)pentyl]-(2S)-2,6-diaminohexanamide (22) exhibited curative activity at 50 mg/kg against P. yoelii nigeriensis in mice and emerged as the most potent analogue against multi-drug resistant strain. The results of this study represent development of highly potent 8-quinolinamines for antimalarial drug development. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.028
• 作为产物：
  描述：

  4-Ethyl-6-methoxy-5-pentoxyquinolin-8-amine 在 一水合肼 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 32.0h， 生成 N8-(4-amino-1-methylpentyl)-4-ethyl-6-methoxy-5-pentyloxy-8-quinolinamine
  参考文献：
  名称：

  新型 8-喹啉胺的合成、抗疟、抗利什曼尼、抗菌、细胞毒性和高铁血红蛋白 (MetHB) 形成活性。

  摘要：

  我们报告了两个系列 8-喹啉胺的合成、体外抗原虫（针对疟原虫和利什曼原虫）、抗菌、细胞毒性（Vero 和 MetHb 产生特性）以及体内抗疟活性。N1-{4-[2-(叔丁基)-6-甲氧基-8-喹啉氨基]戊基}-(2S/2R)-2-氨基取代酰胺(21-33)和N1-[4-(4-乙基) -6-甲氧基-5-戊氧基-8-喹啉氨基)戊基]-(2S/2R)-2-氨基取代酰胺(51-63)由6-甲氧基-8-硝基喹啉和4-甲氧基-2分六步合成分别为-硝基-5-戊氧基苯胺。几种类似物在体外对恶性疟原虫 D6（氯喹敏感）和 W2（氯喹抗性）克隆表现出良好的抗疟活性，与哺乳动物细胞相比具有高选择性指数。最有前途的类似物 (21-24) 在伯氏疟原虫感染的小鼠模型中也显示出有效的体内抗疟活性。最有趣的是，许多类似物对杜氏利什曼原虫前鞭毛体表现出有前景的体外抗利什曼原虫活性，并对一组病原细菌和真菌表现出抗菌活性。与伯氨喹相比，几种类似物，尤其是

  DOI：

  10.1016/j.bmc.2006.10.036

文献信息

• Synthesis, antiprotozoal, antimicrobial, β-hematin inhibition, cytotoxicity and methemoglobin (MetHb) formation activities of bis(8-aminoquinolines)
  作者：Kirandeep Kaur、Meenakshi Jain、Shabana I. Khan、Melissa R. Jacob、Babu L. Tekwani、Savita Singh、Prati Pal Singh、Rahul Jain

  DOI：10.1016/j.bmc.2010.11.036

  日期：2011.1

  In continuing our search of potent antimalarials based on 8-aminoquinoline structural framework, three series of novel bis(8-aminoquinolines) using convenient one to four steps synthetic procedures were synthesized. The bisquinolines were evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (a panel of pathogenic bacteria and fungi), cytotoxicity

  在继续研究基于 8-氨基喹啉结构框架的有效抗疟药的过程中，使用方便的一到四步合成程序合成了三个系列的新型双（8-氨基喹啉）。对双喹啉类药物的体外抗疟（恶性 疟原虫）、抗利什曼 原虫（多诺瓦尼利什曼原虫）、抗微生物剂（一组致病细菌和真菌）、细胞毒性、β-血红素抑制和高铁血红蛋白 (MetHb) 形成活性进行了评估。与母体药物伯氨喹相比，几种化合物表现出优异的抗疟活性。选择的化合物（44，61和79时在体内血液裂殖抗疟疾活性测试）（Plasmodium berghei ) 显示出有效的血液裂殖体活动。双喹啉的 MetHb 形成可以忽略不计（0.2-1.2%），这突显了它们在治疗葡萄糖-6-磷酸脱氢酶缺乏症患者中的潜力。所述双喹啉类似物（36，73和79）也表现出体外活性antileishmanial看好，和抗菌活性（43，44和76对致病细菌和真菌的面板）。这项研究的结果提供了证据，证明双（8
• 8-Quinolinamines and Their pro prodrug conjugates as potent blood-Schizontocidal antimalarial agents
  作者：Suryanarayana Vangapandu、Sandeep Sachdeva、Meenakshi Jain、Savita Singh、Prati Pal Singh、Chaman Lal Kaul、Rahul Jain

  DOI：10.1016/j.bmc.2003.07.003

  日期：2003.10

  Synthesis and antimalarial activities of N-8-(4-amino-1-methylbutyl)-5-alkoxy-4-ethyl-6-methoxy-8-quinolinamines (5) and their pro prodrug analogues (6-7) prepared by covalently linking 5 to the redox-sensitive (8) and esterase-sensitive (9) linkers through the amide linkage are reported. The most effective 8-quinolinamines [5c (R = C5H11) and 5f (R = C8H17)] A have exhibited in vitro and in vivo biological efficacy superior to that of the standard drug chloroquine against both drug-sensitive and drug-resistant malaria strains. Analogues 6-7 were evaluated for in vivo blood-schizontocidal activity as potential pro prodrug models for the primary amino group containing 8-quinolinamines (5). The most effective pro prodrug analogue (6c) has displayed promising activities against drug-sensitive and drug-resistant strains of Plasmodia in vivo. (C) 2003 Elsevier Ltd. All rights reserved.
• Synthesis, antimalarial, antileishmanial, antimicrobial, cytotoxicity, and methemoglobin (MetHB) formation activities of new 8-quinolinamines
  作者：Kirandeep Kaur、Sanjay R. Patel、Premanand Patil、Meenakshi Jain、Shabana I. Khan、Melissa R. Jacob、Shobana Ganesan、Babu L. Tekwani、Rahul Jain

  DOI：10.1016/j.bmc.2006.10.036

  日期：2007.1

  respectively. Several analogs displayed promising antimalarial activity in vitro against Plasmodium falciparum D6 (chloroquine-sensitive) and W2 (chloroquine-resistant) clones with high selectivity indices versus mammalian cells. The most promising analogs (21-24) also displayed potent antimalarial activity in vivo in a Plasmodium berghei-infected mouse model. Most interestingly, many analogs exhibited promising

  我们报告了两个系列 8-喹啉胺的合成、体外抗原虫（针对疟原虫和利什曼原虫）、抗菌、细胞毒性（Vero 和 MetHb 产生特性）以及体内抗疟活性。N1-4-[2-(叔丁基)-6-甲氧基-8-喹啉氨基]戊基}-(2S/2R)-2-氨基取代酰胺(21-33)和N1-[4-(4-乙基) -6-甲氧基-5-戊氧基-8-喹啉氨基)戊基]-(2S/2R)-2-氨基取代酰胺(51-63)由6-甲氧基-8-硝基喹啉和4-甲氧基-2分六步合成分别为-硝基-5-戊氧基苯胺。几种类似物在体外对恶性疟原虫 D6（氯喹敏感）和 W2（氯喹抗性）克隆表现出良好的抗疟活性，与哺乳动物细胞相比具有高选择性指数。最有前途的类似物 (21-24) 在伯氏疟原虫感染的小鼠模型中也显示出有效的体内抗疟活性。最有趣的是，许多类似物对杜氏利什曼原虫前鞭毛体表现出有前景的体外抗利什曼原虫活性，并对一组病原细菌和真菌表现出抗菌活性。与伯氨喹相比，几种类似物，尤其是
• 8-Quinolinamines conjugated with amino acids are exhibiting potent blood-schizontocidal antimalarial activities
  作者：Suryanarayana Vangapandu、Sandeep Sachdeva、Meenakshi Jain、Savita Singh、Prati Pal Singh、Chaman Lal Kaul、Rahul Jain

  DOI：10.1016/j.bmc.2003.10.028

  日期：2004.1

  Alanine, lysine, ornithine and valine conjugated to primaquine and other 8-quinolinamine antinialarials were prepared for blood-schizontocidal antimalarial activity evaluation. The analogues were examined in vivo against Plasmodium berghei (drug-sensitive strain) and Plasinodium yoelii nigeriensis (highly virulent multi-drug-resistant strain) infected mice models. N-1-[4-(5Butoxy-4-ethyl-6-methoxy-8-quinolylamino)pentyl]-(2S)-2,6-diaminohexanamide (20) which showed curative activity at 5 mg/kg in the P. berghei test emerged as the most effective compound. N-1-[4-(4-Ethyl-5-hexoxy-6-methoxy-8-quinolylamino)pentyl]-(2S)-2,6-diaminohexanamide (22) exhibited curative activity at 50 mg/kg against P. yoelii nigeriensis in mice and emerged as the most potent analogue against multi-drug resistant strain. The results of this study represent development of highly potent 8-quinolinamines for antimalarial drug development. (C) 2003 Elsevier Ltd. All rights reserved.