4-(3-fluorophenoxy)-2-trichloromethylquinazoline | 1334477-28-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3-fluorophenoxy)-2-trichloromethylquinazoline
• 英文别名: 4-(3-Fluorophenoxy)-2-(trichloromethyl)quinazoline
• CAS: 1334477-28-9
• 化学式: C₁₅H₈Cl₃FN₂O
• 分子量: 357.599
• InChiKey: JIJLVMSGAFOXBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-甲基-4(3H)-喹唑酮 在 五氯化磷 、 sodium hydride 、 三氯氧磷 作用下， 以 二甲基亚砜 为溶剂， 反应 24.58h， 生成 4-(3-fluorophenoxy)-2-trichloromethylquinazoline
  参考文献：
  名称：

  Targeting the human malaria parasite Plasmodium falciparum: In vitro identification of a new antiplasmodial hit in 4-phenoxy-2-trichloromethylquinazoline series

  摘要：

  From the promising results we previously obtained in quinazoline series and to complete the evaluation of the in vitro antiplasmodial activity of original 2-trichloromethylquinazolines, we synthesized new quinazolines possessing a variously substituted phenoxy group at position 4 through a simple and efficient two-step-synthesis approach. The studies of their activity toward the multi-resistant W2 Plasmodium falciparum strain and of their cytotoxicity on the human hepatocyte HepG2 cell line highlighted a hit compound (molecule 7) displaying a W2 IC(50) value of 1.1 mu M and a HepG2 CC(50) value of 50 mu M, comparable to chloroquine and doxycycline. Structure-activity- and toxicity relationships indicate that the trichloromethyl group plays a key role in the antiplasmodial activity of such chemical scaffold and also that the phenoxy group substitution as a direct influence on the molecules selectivity. Moreover, molecule 7 displays significant specific activity against the Plasmodium genus in comparison with Toxoplasma and does not show any mutagenic property at the Ames test. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.021

文献信息

• Targeting the human malaria parasite Plasmodium falciparum: In vitro identification of a new antiplasmodial hit in 4-phenoxy-2-trichloromethylquinazoline series
  作者：Caroline Castera-Ducros、Nadine Azas、Pierre Verhaeghe、Sébastien Hutter、Philippe Garrigue、Aurélien Dumètre、Litaty Mbatchi、Michèle Laget、Vincent Remusat、France Sifredi、Sylvain Rault、Pascal Rathelot、Patrice Vanelle

  DOI：10.1016/j.ejmech.2011.06.021

  日期：2011.9

  From the promising results we previously obtained in quinazoline series and to complete the evaluation of the in vitro antiplasmodial activity of original 2-trichloromethylquinazolines, we synthesized new quinazolines possessing a variously substituted phenoxy group at position 4 through a simple and efficient two-step-synthesis approach. The studies of their activity toward the multi-resistant W2 Plasmodium falciparum strain and of their cytotoxicity on the human hepatocyte HepG2 cell line highlighted a hit compound (molecule 7) displaying a W2 IC(50) value of 1.1 mu M and a HepG2 CC(50) value of 50 mu M, comparable to chloroquine and doxycycline. Structure-activity- and toxicity relationships indicate that the trichloromethyl group plays a key role in the antiplasmodial activity of such chemical scaffold and also that the phenoxy group substitution as a direct influence on the molecules selectivity. Moreover, molecule 7 displays significant specific activity against the Plasmodium genus in comparison with Toxoplasma and does not show any mutagenic property at the Ames test. (C) 2011 Elsevier Masson SAS. All rights reserved.