{3-amino-5-[(7-chloro-4-quinolyl)amino]phenyl}methanol | 243989-41-5

• 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-amino-5-[(7-chloro-4-quinolyl)amino]phenyl}methanol
• 英文别名: [3-Amino-5-[(7-chloroquinolin-4-yl)amino]phenyl]methanol
• CAS: 243989-41-5
• 化学式: C₁₆H₁₄ClN₃O
• 分子量: 299.76
• InChiKey: ZVHATLRCKQOOHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  71.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {3-amino-5-[(7-chloro-4-quinolyl)amino]phenyl}methanol 在 N-乙基哌啶 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成
  参考文献：
  名称：

  Synthesis and in Vitro and in Vivo Antimalarial Activity of New 4-Anilinoquinolines

  摘要：

  A new series of 4-anilinoquinolines with two proton-accepting side chains has been synthesized. Antimalarial activity and levels of cytotoxicity upon both MRC-5 cells and macrophages were found to be highly dependent upon the features of these side chains. Several compounds were found to be active in the low nanomolar range, against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. From among them, a morpholino derivative cured mice infected by Plasmodium berghei and displayed a lower toxicity than amodiaquine upon mouse macrophages.

  DOI：

  10.1021/jm010842o
• 作为产物：
  描述：

  4,7-二氯喹啉 、 3,5-diaminobenzyl alcohol dihydrochloride 在 N-甲基吗啉 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 72.0h， 以88%的产率得到{3-amino-5-[(7-chloro-4-quinolyl)amino]phenyl}methanol
  参考文献：
  名称：

  "One-Pot" Synthesis and Antimalarial Activity of Formamidine Derivatives of 4-Anilinoquinoline.

  摘要：

  阿莫地喹（AQ）是一种抗疟疾药物，对氯喹耐药性恶性疟原虫株有效，但由于相关的肝毒性和粒细胞缺乏症，其临床应用受到严重限制。据报道，甲脒类药物可能转化为AQ衍生物，并采用“一锅法”合成。与AQ相比，新化合物对人类胚胎肺细胞和小鼠腹膜巨噬细胞没有体外细胞毒性。其中一种化合物在感染伯氏疟原虫的小鼠体内显示出强大的活性。通过还原胺化作用转化这种化合物，可以得到一种新型的AQ衍生物，其体外活性与AQ相似，但不会产生有毒的醌亚胺。

  DOI：

  10.1248/cpb.49.933

文献信息

• Synthesis and antimalarial activity of new analogues of amodiaquine
  作者：Sandrine Delarue-Cochin、Emilia Paunescu、Louis Maes、Elisabeth Mouray、Christian Sergheraert、Philippe Grellier、Patricia Melnyk

  DOI：10.1016/j.ejmech.2007.03.008

  日期：2008.2

  In order to determine the real significance of the 4'-phenolic group in the antimalarial activity and/or cytotoxicity of amodiaquine (AQ), analogues for which this functionality was shifted or modified were synthesized. Good in vitro antimalarial activity was obtained for compounds unable to form intramolecular hydrogen bond. Among the compounds synthesized, new amino derivative 5 displayed the greatest

  为了确定4'-酚基在氨二喹（AQ）的抗疟活性和/或细胞毒性中的真正意义，合成了对其功能进行了转移或修饰的类似物。对于无法形成分子内氢键的化合物，其体外抗疟活性良好。在合成的化合物中，新的氨基衍生物5对测试的对CQ耐药性最高的菌株表现出最大的选择性指数，并且在感染了伯氏疟原虫的小鼠中具有活性。
• Synthesis and antimalarial activity of carbamate and amide derivatives of 4-anilinoquinoline
  作者：Sandrine Delarue-Cochin、Philippe Grellier、Louis Maes、Elisabeth Mouray、Christian Sergheraert、Patricia Melnyk

  DOI：10.1016/j.ejmech.2007.11.003

  日期：2008.10

  A series of 4-anilinoquinolines bearing an amino side chain linked to the aromatic ring with a carbamate or an amide bond were synthesized and evaluated for their antimalarial activity and their cytotoxicity upon MRC-5 cells. Among the 17 compounds, a majority was found to be active in the low nanomolar range against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro

  合成了一系列带有通过氨基甲酸酯或酰胺键与芳香环连接的氨基侧链的4-苯胺基喹啉，并评估了它们的抗疟活性和对MRC-5细胞的细胞毒性。在这17种化合物中，大多数化合物在体外对恶性疟原虫的氯喹敏感和耐药菌株具有较低的纳摩尔浓度，且具有较低的细胞毒性。然后在受伯氏疟原虫感染的小鼠上测试了两种化合物，发现它们具有合理的体内活性。
• PyBroP: a convenient activator for the synthesis of formamidines
  作者：Sandrine Delarue、Christian Sergheraert

  DOI：10.1016/s0040-4039(99)01054-0

  日期：1999.7

  PyBroP was used as a convenient coupling reagent in the synthesis of formamidines from aliphatic and aromatic primary amines and N,N-dimethylformamide.

  在由脂族和芳族伯胺与N，N-二甲基甲酰胺合成甲am中，PyBroP用作方便的偶联剂。
• Synthesis and in Vitro and in Vivo Antimalarial Activity of New 4-Anilinoquinolines
  作者：Sandrine Delarue、Sophie Girault、Louis Maes、Marie-Ange Debreu-Fontaine、Mehdi Labaeïd、Philippe Grellier、Christian Sergheraert

  DOI：10.1021/jm010842o

  日期：2001.8.1

  A new series of 4-anilinoquinolines with two proton-accepting side chains has been synthesized. Antimalarial activity and levels of cytotoxicity upon both MRC-5 cells and macrophages were found to be highly dependent upon the features of these side chains. Several compounds were found to be active in the low nanomolar range, against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. From among them, a morpholino derivative cured mice infected by Plasmodium berghei and displayed a lower toxicity than amodiaquine upon mouse macrophages.
• "One-Pot" Synthesis and Antimalarial Activity of Formamidine Derivatives of 4-Anilinoquinoline.
  作者：Sandrine DELARUE、Sophie GIRAULT、Fouad DALI ALI、Louis MAES、Philippe GRELLIER、Christian SERGHERAERT

  DOI：10.1248/cpb.49.933

  日期：——

  Amodiaquine (AQ) is an antimalarial which is effective against chloroquino-resistant strains of Plasmodium falciparum but whose clinical use is severely restricted because of associated hepatotoxicity and agranulocytosis. “One-pot” synthesis of formamidines likely to be transformed into AQ derivatives is reported. Compared with AQ, the new compounds were devoid of in vitro cytotoxicity upon human embryonic lung cells and mouse peritoneal macrophages. One showed a potent in vivo activity in mice infected with P. berghei. Transformation of this compound by reductive amination led to a new type of AQ derivatives that displayed an in vitro activity similar to that of AQ but did not lead to toxic quinone-imines.

  阿莫地喹（AQ）是一种抗疟疾药物，对氯喹耐药性恶性疟原虫株有效，但由于相关的肝毒性和粒细胞缺乏症，其临床应用受到严重限制。据报道，甲脒类药物可能转化为AQ衍生物，并采用“一锅法”合成。与AQ相比，新化合物对人类胚胎肺细胞和小鼠腹膜巨噬细胞没有体外细胞毒性。其中一种化合物在感染伯氏疟原虫的小鼠体内显示出强大的活性。通过还原胺化作用转化这种化合物，可以得到一种新型的AQ衍生物，其体外活性与AQ相似，但不会产生有毒的醌亚胺。