2-chloromethyl-4-[(7-chloroquinolin-4-yl)amino]phenol hydrochloride | 1203701-93-2

• 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: 2-chloromethyl-4-[(7-chloroquinolin-4-yl)amino]phenol hydrochloride
• 英文别名: 2-(Chloromethyl)-4-[(7-chloroquinolin-4-yl)amino]phenol;hydrochloride
• CAS: 1203701-93-2
• 化学式: C₁₆H₁₂Cl₂N₂O*ClH
• 分子量: 355.651
• InChiKey: VRGXYLYRGWYYRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  22
• 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：
  45.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloromethyl-4-[(7-chloroquinolin-4-yl)amino]phenol hydrochloride 、 3-amino-1-propanol nitrate 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 7-chloro-4-{[4-hydroxy-3-({[3-(nitrooxy)propyl]ammonio}methyl)phenyl]amino}quinoline
  参考文献：
  名称：

  Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria

  摘要：

  The synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy NO-donor substructures are described. The synthesised compounds were tested in vitro against both the chloroquine sensitive, 010 and the chloroquine resistant, W-2 strains of Plasmodium falciparum (P falciparum). Most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. By comparing the activities of simple related structures devoid of the ability to release NO, it appears that the contribution of NO to the antiplasmodial action in vitro is marginal. All the compounds were able to relax rat aorta strips with a NO-dependent mechanism, thus showing their capacity to release NO in the vessels. A preliminary in vivo study using Plasmodium berghei ANKA-infected mice showed a trend for prolonged survival of mice with cerebral malaria treated with compound 40, which is potent and fast amodiaquine-derived NO-donor, when compared with amodiaquine alone or with compound 31, a milder NO-donor. The two compounds showed in vivo antiplasmodial activity similar to that of amodiaquine. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.029
• 作为产物：
  描述：

  4-[(7-chloroquinolin-4-yl)amino]-2-(hydroxymethyl)phenol hydrochloride 在 盐酸 、 水 作用下， 反应 18.0h， 以91%的产率得到2-chloromethyl-4-[(7-chloroquinolin-4-yl)amino]phenol hydrochloride
  参考文献：
  名称：

  在基础侧链上修饰的具有一系列体外抗疟原虫和抗疟原虫活性的新系列氨二喹类似物

  摘要：

  报道了带有修饰的侧向基本链的新型氨二喹衍生物的合成和研究，所述衍生物为具有抗疟和抗疟疾活性的新药剂。该化合物在体外测试了抗利什曼原虫MHOM / ET / 67 / HU3和2株恶性疟原虫，3D7和K1菌株。所有化合物均显示出复杂的电离曲线。在生理pH下，离子化形式与不带电形式处于平衡状态，而在酸性pH下，所有产物主要以质子化形式存在。抗原生动物的概况表明，所有衍生物都具有抗疟和抗疟疾活性。有趣的是阿莫地喹，一些合成的衍生物（一起11，12，15，27，34），显示在低微摩尔范围antileishmanial活性，尽管这些化合物还细胞毒性和具有窄的治疗窗，大部分合成的化合物的证明是有效的抗疟药，其中的几个显示了针对氯喹良好的活性抗K1菌株。

  DOI：

  10.1016/j.ejmech.2009.09.012

文献信息

• Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria
  作者：Massimo Bertinaria、Stefano Guglielmo、Barbara Rolando、Marta Giorgis、Cristina Aragno、Roberta Fruttero、Alberto Gasco、Silvia Parapini、Donatella Taramelli、Yuri C. Martins、Leonardo J.M. Carvalho

  DOI：10.1016/j.ejmech.2011.02.029

  日期：2011.5

  The synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy NO-donor substructures are described. The synthesised compounds were tested in vitro against both the chloroquine sensitive, 010 and the chloroquine resistant, W-2 strains of Plasmodium falciparum (P falciparum). Most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. By comparing the activities of simple related structures devoid of the ability to release NO, it appears that the contribution of NO to the antiplasmodial action in vitro is marginal. All the compounds were able to relax rat aorta strips with a NO-dependent mechanism, thus showing their capacity to release NO in the vessels. A preliminary in vivo study using Plasmodium berghei ANKA-infected mice showed a trend for prolonged survival of mice with cerebral malaria treated with compound 40, which is potent and fast amodiaquine-derived NO-donor, when compared with amodiaquine alone or with compound 31, a milder NO-donor. The two compounds showed in vivo antiplasmodial activity similar to that of amodiaquine. (C) 2011 Elsevier Masson SAS. All rights reserved.
• A new series of amodiaquine analogues modified in the basic side chain with in vitro antileishmanial and antiplasmodial activity
  作者：Stefano Guglielmo、Massimo Bertinaria、Barbara Rolando、Marco Crosetti、Roberta Fruttero、Vanessa Yardley、Simon L. Croft、Alberto Gasco

  DOI：10.1016/j.ejmech.2009.09.012

  日期：2009.12

  antileishmanial activity. Interestingly amodiaquine, together with some synthesised derivatives (11, 12, 15, 27, 34), displayed antileishmanial activity in the low micromolar range, although these compounds were also cytotoxic and have a narrow therapeutic window, most of the synthesised compounds proved to be potent antimalarials, a few of them showing a good activity against the chloroquine resistant K1

  报道了带有修饰的侧向基本链的新型氨二喹衍生物的合成和研究，所述衍生物为具有抗疟和抗疟疾活性的新药剂。该化合物在体外测试了抗利什曼原虫MHOM / ET / 67 / HU3和2株恶性疟原虫，3D7和K1菌株。所有化合物均显示出复杂的电离曲线。在生理pH下，离子化形式与不带电形式处于平衡状态，而在酸性pH下，所有产物主要以质子化形式存在。抗原生动物的概况表明，所有衍生物都具有抗疟和抗疟疾活性。有趣的是阿莫地喹，一些合成的衍生物（一起11，12，15，27，34），显示在低微摩尔范围antileishmanial活性，尽管这些化合物还细胞毒性和具有窄的治疗窗，大部分合成的化合物的证明是有效的抗疟药，其中的几个显示了针对氯喹良好的活性抗K1菌株。