7-[(7-Chloro-4-quinolyl)amino]-3-ethyl-quinazolin-4-one | 1414781-94-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-[(7-Chloro-4-quinolyl)amino]-3-ethyl-quinazolin-4-one
• 英文别名: 7-[(7-chloroquinolin-4-yl)amino]-3-ethylquinazolin-4-one
• CAS: 1414781-94-4
• 化学式: C₁₉H₁₅ClN₄O
• 分子量: 350.807
• InChiKey: BTZVUGIPNPWOIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-[(7-Chloro-4-quinolyl)amino]-3-ethyl-quinazolin-4-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以70%的产率得到N-(7-chloro-4-quinolyl)-3-ethyl-2,4-dihydro-1H-quinazolin-7-amine
  参考文献：
  名称：

  Mimicking the Intramolecular Hydrogen Bond: Synthesis, Biological Evaluation, and Molecular Modeling of Benzoxazines and Quinazolines as Potential Antimalarial Agents

  摘要：

  The intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to play an important role in their antimalarial activities. Here we describe isoquine-based compounds in which the intramolecular H-bond is mimicked by a methylene linker. The antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3-quinazolin-4-ones were examined in vitro (against Plasmodium falciparum) and in vivo (against Plasmodium berghei). Compounds 6b,c caused modest inhibition of chloroquine transport via the parasite's "chloroquine resistance transporter" (PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound 6c emerged from this work as the most promising analogue of the series; it possessed low toxicity and good antimalarial activity when administered orally to P. berghei-infected mice.

  DOI：

  10.1021/jm300831b
• 作为产物：
  描述：

  N-ehyl-2-amino-4-nitrobenzamide 在 铁粉 、 calcium chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 53.0h， 生成 7-[(7-Chloro-4-quinolyl)amino]-3-ethyl-quinazolin-4-one
  参考文献：
  名称：

  Mimicking the Intramolecular Hydrogen Bond: Synthesis, Biological Evaluation, and Molecular Modeling of Benzoxazines and Quinazolines as Potential Antimalarial Agents

  摘要：

  The intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to play an important role in their antimalarial activities. Here we describe isoquine-based compounds in which the intramolecular H-bond is mimicked by a methylene linker. The antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3-quinazolin-4-ones were examined in vitro (against Plasmodium falciparum) and in vivo (against Plasmodium berghei). Compounds 6b,c caused modest inhibition of chloroquine transport via the parasite's "chloroquine resistance transporter" (PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound 6c emerged from this work as the most promising analogue of the series; it possessed low toxicity and good antimalarial activity when administered orally to P. berghei-infected mice.

  DOI：

  10.1021/jm300831b

文献信息

• Mimicking the Intramolecular Hydrogen Bond: Synthesis, Biological Evaluation, and Molecular Modeling of Benzoxazines and Quinazolines as Potential Antimalarial Agents
  作者：Sandra Gemma、Caterina Camodeca、Margherita Brindisi、Simone Brogi、Gagan Kukreja、Sanil Kunjir、Emanuele Gabellieri、Leonardo Lucantoni、Annette Habluetzel、Donatella Taramelli、Nicoletta Basilico、Roberta Gualdani、Francesco Tadini-Buoninsegni、Gianluca Bartolommei、Maria Rosa Moncelli、Rowena E. Martin、Robert L. Summers、Stefania Lamponi、Luisa Savini、Isabella Fiorini、Massimo Valoti、Ettore Novellino、Giuseppe Campiani、Stefania Butini

  DOI：10.1021/jm300831b

  日期：2012.12.13

  The intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to play an important role in their antimalarial activities. Here we describe isoquine-based compounds in which the intramolecular H-bond is mimicked by a methylene linker. The antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3-quinazolin-4-ones were examined in vitro (against Plasmodium falciparum) and in vivo (against Plasmodium berghei). Compounds 6b,c caused modest inhibition of chloroquine transport via the parasite's "chloroquine resistance transporter" (PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound 6c emerged from this work as the most promising analogue of the series; it possessed low toxicity and good antimalarial activity when administered orally to P. berghei-infected mice.