4-甲基-5,6-二甲氧基-8-硝基喹啉 | 64992-96-7

• 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
• 中文名称: 4-甲基-5,6-二甲氧基-8-硝基喹啉
• 英文名称: 5,6-dimethoxy-4-methyl-8-nitroquinoline
• 英文别名: 4-Methyl-5,6-dimethoxy-8-nitroquinoline
• CAS: 64992-96-7
• 化学式: C₁₂H₁₂N₂O₄
• 分子量: 248.238
• InChiKey: MWNVHYGVJILSRP-UHFFFAOYSA-N

物化性质

• 熔点：
  122-125 °C(Solv: methanol (67-56-1))
• 沸点：
  425.4±40.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  77.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-甲基-5,6-二甲氧基-8-硝基喹啉 在 镍 盐酸 、 氢氧化钾 、 氢气 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙二醇乙醚 、 乙醇 为溶剂， 80.0 ℃ 、310.27 kPa 条件下， 反应 32.25h， 生成 8-amino-6-methoxy-4-methyl-5-(3-trifluoromethylphenoxy)quinoline
  参考文献：
  名称：

  Antimalarials. 14. 5-(Aryloxy)-4-methylprimaquine analogs. A highly effective series of blood and tissue schizonticidal agents

  摘要：

  A series of five 5-(aryloxy)-4-methylprimaquine analogues has been prepared and evaluated for antimalarial activity. The compounds were tested for suppressive activity against Plasmodium berghei in mice and for radical curative activity against Plasmodium cynomolgi in the rhesus monkey. The compounds were not only significantly superior to primaquine as radical curative agents but also were suprisingly highly effective as suppressive agents.

  DOI：

  10.1021/jm00351a017
• 作为产物：
  描述：

  邻苯二甲醚 在 磷酸 、 硫酸 、 硝酸 、 铁粉 、 溶剂黄146 作用下， 反应 7.0h， 生成 4-甲基-5,6-二甲氧基-8-硝基喹啉
  参考文献：
  名称：

  探索未开发的化学空间：合理鉴定具有抗疟特性的新型他非诺喹类似物

  摘要：

  专利倾向于定义由马库什结构的组合性质描述的巨大化学空间。然而，新主要活性成分的优化通常是由简单的 Free Wilson 方法驱动的。这一过程导致对命中化合物附近的化学空间进行高度集中的研究，留下许多可能存在高度生物活性储层的未探索区域。这项研究旨在证明，这种公开的化学空间可以隐藏具有值得研究的有趣潜在生物活性的化合物。这强调了拓宽传统策略之外的方法的价值和必要性。因此，我们主张采用一种在早期药物发现阶段可能更有效的替代方法。我们选择2018年FDA批准的单剂量根治疟疾药物他非诺喹的案例来说明这一过程。通过对他非诺喹化学空间的深入探索，合理鉴定并合成了七种具有潜在抗疟活性的化合物。这一小组代表了迄今为止报道的 58 种类似物尚未探索的化学多样性。经过生物学评估，结果证明我们的合理设计方法已被证明是一种非常有效的探索性方法，适合早期药物发现阶段。

  DOI：

  10.1016/j.bioorg.2024.107472
• 作为试剂：
  描述：

  钠 、 5-chloro-6-methoxy-4-methyl-8-nitroquinoline 、 吡啶 、 甲醇 在 碳 、 甲醇 、 4-甲基-5,6-二甲氧基-8-硝基喹啉 作用下， 反应 64.0h， 以to give an additional 15 g of 5,6-dimethoxy-4-methyl-8-nitroquinoline的产率得到4-甲基-5,6-二甲氧基-8-硝基喹啉
  参考文献：
  名称：

  5-(Straight chain 3-12 carbon alkoxy)-8-quinolinamines and their use for

  摘要：

  已经通过具有以下式子的5-氧基-前胡碱类似物实现了改进的疟疾化疗方法：##STR1## 其中R.sub.4代表氢或甲基基团，R代表含有3至12个碳原子的烷基基团及其药物可接受的盐，其中形成盐的酸可以是有机或无机的。这些前胡碱相关化合物通过对哺乳动物寄主的血液、形成组织或血液和形成组织中可能存在的疟原虫发挥疟原虫杀灭作用，从而改善了疟疾的化疗效果。这种广泛而实用的效果谱区别于所述的前胡碱类似物，可以通过注射或口服给感染的动物。

  公开号：

  US04554279A1

文献信息

• Process for production of 8-NHR quinolines
  申请人：The United States of America as represented by the Secretary of the Army

  公开号：US04167638A1

  公开（公告）日：1979-09-11

  An improved process for producing 8-NHR quinolines from 8-aminoquinolines disclosed. The process comprises reacting 8-aminoquinolines with a substituted alkyl halide in the presence of an amine having a boiling point of 80.degree.-90.degree. C. The amine functions as an acid acceptor whereby the amine salt formed may be efficiently separated from the 8-NHR quinoline formed without expensive or time consuming purification steps. The reaction may be carried out in the presence of a solvent such as an alcohol.

  一种改进的方法用于从8-氨基喹啉制备8-NHR喹啉。该方法包括在存在沸点为80度至90度的胺的情况下，将8-氨基喹啉与取代烷基卤化物反应。胺起到酸受体的作用，从而形成的胺盐可以在无需昂贵或耗时的纯化步骤的情况下有效地与形成的8-NHR喹啉分离。反应可以在存在溶剂（如醇类）的情况下进行。
• Process for preparation of ring-substituted 8-aminoquinoline analogs as antimalarial agents
  申请人：——

  公开号：US20040192724A1

  公开（公告）日：2004-09-30

  The present invention is concerned with the development of novel 8-aminoquinoline analogs in the treatment and prevention of malaria and the said compound has broad spectrum of activity against the blood as well as tissue stages of the human malaria parasites makes these compounds very attractive in the cure and prevention of malaria caused by drug-sensitive and multidrug resistant strains and also it is expected that development of these compounds as ideal antimalarial agents may lead to suppression as well as radical cure of the malaria infection with single drug therapy.

  本发明涉及新型8-氨基喹啉类似物在治疗和预防疟疾方面的开发，所述化合物对人类疟原虫的血期及组织期具有广谱活性，使得这些化合物在治疗和预防由药物敏感和多药耐药菌株引起的疟疾方面极具吸引力。同时，预期将这些化合物开发为理想的抗疟药物可能会导致单一药物疗法既能抑制又能根治疟疾感染。
• 4-Methyl-5-(unsubstituted and substituted
  申请人：The United States of America as represented by the Secretary of the Army

  公开号：US04431807A1

  公开（公告）日：1984-02-14

  Compounds of the class including 4-methyl-5-(unsubstituted and substituted henoxy)-6-methoxy-8-(aminoalkylamino)quinolines as the free bases and pharmaceutically acceptable acid amine salts are described. The compounds are highly effective antimalarial agents which possess, surprisingly, both tissue schizonticidal (radical curative) and blood schizonticidal (suppressive) activity. In addition, these drugs have significantly better therapeutics indices than primaquine which is the current tissue schizonticidal drug of choice. Primaquine possesses no useful blood schizonticidal activity at tolerated dose levels.

  该类化合物包括4-甲基-5-（未取代和取代henoxy）-6-甲氧基-8-（氨基烷基氨基）喹啉作为自由碱和药学上可接受的酸胺盐。这些化合物是高效的抗疟疾药物，令人惊讶的是，它们具有组织红细胞分裂体杀灭（根治性）和血液红细胞分裂体杀灭（抑制性）活性。此外，这些药物的治疗指数显著优于普利昂奎，后者是目前组织红细胞分裂体杀灭药物的首选药物。普利昂奎在可耐受的剂量水平下没有有用的血液红细胞分裂体杀灭活性。
• 4,5-Disubstituted primaquine analogues as potential antimalarial agents
  作者：F. Ivy Carroll、Bertold D. Berrang、Carl P. Linn

  DOI：10.1021/jm00159a042

  日期：1986.9

  Three 4,5-disubstituted primaquine analogues were synthesized and evaluated for radical curative activity against Plasmodium cynomolgi in rhesus monkeys. One of the compounds showed moderate activity; however, none of the three compounds were as active as the lead compounds 5-methoxy-4-methylprimaquine and 4-(methoxy-methyl)-5-[m-(trifluoromethyl)phenoxy]primaquine.

  合成了三个4，5-二取代的伯氨喹类似物，并评估了在猕猴中针对食蟹猴的自由基治疗活性。其中一种化合物显示出中等活性。然而，这三种化合物都没有活性的先导化合物5-甲氧基-4-甲基伯氨喹和4-（甲氧基甲基）-5- [间-（三氟甲基）苯氧基]伯氨喹。
• 4-methyl-5-(unsubstituted and substituted
  申请人：The United States of America as represented by the Secretary of the Army

  公开号：US04617394A1

  公开（公告）日：1986-10-14

  Compounds of the class including 4-methyl-5-(unsubstituted and substituted phenoxy)-2,6-dimethoxy-8-(aminoalkylamino)quinolines as the free bases and pharmaceutically acceptable acid amine salts are described. The compounds are highly effective antimalarial agents which possess both tissue schizonticidal (radical curative) and blood schizonticidal (suppressive) acitivity. In addition, these drugs have significantly better therapeutic indices than primaquine which is the current tissue schizonticidal drug of choice. Primaquine possesses no useful blood schizonticidal activity at tolerated dose levels. The new 2-methoxy substituted compounds produce markedly less methemoglobin at effective dose levels and thus permit a higher degree of safety than analogs which are unsubstituted in the 2-position.

  本类化合物包括4-甲基-5-（未取代和取代的苯氧基）-2,6-二甲氧基-8-（氨基烷基氨基）喹啉作为自由碱和药学上可接受的酸胺盐。这些化合物是高效的抗疟疾药物，具有组织无性繁殖体杀灭（根治）和血液无性繁殖体杀灭（抑制）活性。此外，这些药物的治疗指数显著优于目前选择的组织无性繁殖体杀灭药物-盐酸伯氨喹。在可耐受的剂量水平下，盐酸伯氨喹没有有用的血液无性繁殖体杀灭活性。新的2-甲氧基取代化合物在有效剂量水平下产生的甲血红蛋白明显较少，因此比2-位未取代的类似物具有更高的安全性。