N-[2-[(7-chloro-4-quinolyl)amino]ethyl]-N-[2-(cyclohexylamino)-2-oxo-ethyl]-3-(8-hydroxy-3-methyl-1,4-dioxo-2-naphthyl)propanamide | 1319718-33-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[2-[(7-chloro-4-quinolyl)amino]ethyl]-N-[2-(cyclohexylamino)-2-oxo-ethyl]-3-(8-hydroxy-3-methyl-1,4-dioxo-2-naphthyl)propanamide
• 英文别名: N-[2-[(7-chloroquinolin-4-yl)amino]ethyl]-N-[2-(cyclohexylamino)-2-oxoethyl]-3-(8-hydroxy-3-methyl-1,4-dioxonaphthalen-2-yl)propanamide
• CAS: 1319718-33-6
• 化学式: C₃₃H₃₅ClN₄O₅
• 分子量: 603.118
• InChiKey: RISFEOQBJZLAQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  兰雪醌 在 ammonium persulfate 、 silver nitrate 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 5.0h， 生成 N-[2-[(7-chloro-4-quinolyl)amino]ethyl]-N-[2-(cyclohexylamino)-2-oxo-ethyl]-3-(8-hydroxy-3-methyl-1,4-dioxo-2-naphthyl)propanamide
  参考文献：
  名称：

  Effects of highly active novel artemisinin–chloroquinoline hybrid compounds on β-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum

  摘要：

  4-Aminoquinolines were hybridized with artemisinin and 1,4-naphthoquinone derivatives via the Ugi-four-component condensation reaction, and their biological activities investigated. The artemisinin-containing compounds 6a-c and its salt 6c-citrate were the most active target compounds in the antiplasmodial assays. However, despite the potent in vitro activities, they also displayed cytotoxicity against a mammalian cell-line, and had lower therapeutic indices than chloroquine. Morphological changes in parasites treated with these artemisinin-containing hybrid compounds were similar to those observed after addition of artemisinin. These hybrid compounds appeared to share mechanism(s) of action with both chloroquine and artemisinin: they exhibited potent beta-hematin inhibitory activities; they caused an increase in accumulation of hemoglobin within the parasites that was intermediate between the increase observed with artesunate and chloroquine; and they also appeared to inhibit endocytosis as suggested by the decrease in the number of transport vesicles in the parasites. No cross-resistance with chloroquine was observed for these hybrid compounds, despite the fact that they contained the chloroquinoline moiety. The hybridization strategy therefore appeared to be borrowing the best from both classes of antimalarials. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2011.04.018

文献信息

• Effects of highly active novel artemisinin–chloroquinoline hybrid compounds on β-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum
  作者：Tzu-Shean Feng、Eric M. Guantai、Margo Nell、Constance E.J. van Rensburg、Kanyile Ncokazi、Timothy J. Egan、Heinrich C. Hoppe、Kelly Chibale

  DOI：10.1016/j.bcp.2011.04.018

  日期：2011.8

  4-Aminoquinolines were hybridized with artemisinin and 1,4-naphthoquinone derivatives via the Ugi-four-component condensation reaction, and their biological activities investigated. The artemisinin-containing compounds 6a-c and its salt 6c-citrate were the most active target compounds in the antiplasmodial assays. However, despite the potent in vitro activities, they also displayed cytotoxicity against a mammalian cell-line, and had lower therapeutic indices than chloroquine. Morphological changes in parasites treated with these artemisinin-containing hybrid compounds were similar to those observed after addition of artemisinin. These hybrid compounds appeared to share mechanism(s) of action with both chloroquine and artemisinin: they exhibited potent beta-hematin inhibitory activities; they caused an increase in accumulation of hemoglobin within the parasites that was intermediate between the increase observed with artesunate and chloroquine; and they also appeared to inhibit endocytosis as suggested by the decrease in the number of transport vesicles in the parasites. No cross-resistance with chloroquine was observed for these hybrid compounds, despite the fact that they contained the chloroquinoline moiety. The hybridization strategy therefore appeared to be borrowing the best from both classes of antimalarials. (C) 2011 Elsevier Inc. All rights reserved.