5-isopropyloxycarbonyl-6-methyl-4-(4-nitrophenyl)-2-[3-(7-chloroquinolin-4-ylamino)propylamino]pyrimidine | 1376766-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-isopropyloxycarbonyl-6-methyl-4-(4-nitrophenyl)-2-[3-(7-chloroquinolin-4-ylamino)propylamino]pyrimidine
• 英文别名: Isopropyl 2-[3-[(7-chloro-4-quinolyl)amino]propylamino]-4-methyl-6-(4-nitrophenyl)pyrimidine-5-carboxylate；propan-2-yl 2-[3-[(7-chloroquinolin-4-yl)amino]propylamino]-4-methyl-6-(4-nitrophenyl)pyrimidine-5-carboxylate
• CAS: 1376766-57-2
• 化学式: C₂₇H₂₇ClN₆O₄
• 分子量: 535.002
• InChiKey: VCEBTDHLDDPAQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-isopropoxycarbonyl-6-methyl-4-(4-nitrophenyl)pyrimidin-2(1H)-one 在 potassium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 生成 5-isopropyloxycarbonyl-6-methyl-4-(4-nitrophenyl)-2-[3-(7-chloroquinolin-4-ylamino)propylamino]pyrimidine
  参考文献：
  名称：

  2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis, biological activity, structure–activity relationship and mode of action studies

  摘要：

  2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious protocol. Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQ(S) (3D7) and drug-resistant CQ(R) (K1) strains of Plasmodium falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[(7-chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the lowest IC50 (3.6 nM) value (56-fold less than CQ) against CQ(R) strain. Structure activity profile and binding with heme, mu-oxo-heme have been studied. Binding assays with DNA revealed better binding with target parasite type AT rich pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic. Molecular docking analysis with Pf DHFR allowed identification of stabilizing interactions. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.007

文献信息

• 2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis, biological activity, structure–activity relationship and mode of action studies
  作者：Kamaljit Singh、Hardeep Kaur、Kelly Chibale、Jan Balzarini、Susan Little、Prasad V. Bharatam

  DOI：10.1016/j.ejmech.2012.03.007

  日期：2012.6

  2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious protocol. Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQ(S) (3D7) and drug-resistant CQ(R) (K1) strains of Plasmodium falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[(7-chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the lowest IC50 (3.6 nM) value (56-fold less than CQ) against CQ(R) strain. Structure activity profile and binding with heme, mu-oxo-heme have been studied. Binding assays with DNA revealed better binding with target parasite type AT rich pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic. Molecular docking analysis with Pf DHFR allowed identification of stabilizing interactions. (C) 2012 Elsevier Masson SAS. All rights reserved.