(3R,5aS,6R,8aS,9R,12R,12aR)-11-((4-fluorobenzyl)amino)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-10(3H)-one | 1569269-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (3R,5aS,6R,8aS,9R,12R,12aR)-11-((4-fluorobenzyl)amino)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-10(3H)-one
• 英文别名: (1R,4S,5R,8S,9R,12R,13R)-11-[(4-fluorophenyl)methylamino]-1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one
• CAS: 1569269-82-4
• 化学式: C₂₂H₂₉FN₂O₄
• 分子量: 404.482
• InChiKey: KJAJPXAIACKJOP-ZJHNIPSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  60
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  青蒿素 在 sodium tetrahydroborate 、 一水合肼 作用下， 以 甲醇 、 苯 为溶剂， 反应 7.0h， 生成 (3R,5aS,6R,8aS,9R,12R,12aR)-11-((4-fluorobenzyl)amino)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-10(3H)-one
  参考文献：
  名称：

  New Orally Active Amino- and Hydroxy-Functionalized 11-Azaartemisinins and Their Derivatives with High Order of Antimalarial Activity against Multidrug-Resistant Plasmodium yoelii in Swiss Mice1

  摘要：

  By use of artemisinin 1 as the starting material, two new amino- and hydroxy-functionalized 11-azaartemisinins 9 and 11 and their derivatives 12a-g, 13a-g, 14a-g, and 15a-c have been prepared and screened for antimalarial activity by oral route against multidrug-resistant Plasmodium yoelii in Swiss mice. While azaartemisinins 9 and 11 showed only modest activity, several of their derivatives showed high order of antimalarial activity. Biphenyl-based compound 13f, the most active compound of the series, provided 100% and 80% protection to the infected mice at 12 mg/kg × 4 days and 6 mg/kg × 4 days, respectively. Compounds 12f, 13b, 13e, 13g, and 14f showed 100% protection at 12 mg/kg × 4 days, while compounds 12a-c, 14a, 14c-e, 14g, and 15a-c showed similar levels of protection at 24 mg/kg × 4 days. Clinically useful drug β-arteether provided 100% protection at 48 mg/kg × 4 days and 20% protection at 24 mg/kg × 4 days in this model.

  DOI：

  10.1021/jm401774f

文献信息

• New Orally Active Amino- and Hydroxy-Functionalized 11-Azaartemisinins and Their Derivatives with High Order of Antimalarial Activity against Multidrug-Resistant <i>Plasmodium yoelii</i> in Swiss Mice1
  作者：Chandan Singh、Ved Prakash Verma、Mohammad Hassam、Ajit Shankar Singh、Niraj K. Naikade、Sunil K. Puri

  DOI：10.1021/jm401774f

  日期：2014.3.27

  By use of artemisinin 1 as the starting material, two new amino- and hydroxy-functionalized 11-azaartemisinins 9 and 11 and their derivatives 12a-g, 13a-g, 14a-g, and 15a-c have been prepared and screened for antimalarial activity by oral route against multidrug-resistant Plasmodium yoelii in Swiss mice. While azaartemisinins 9 and 11 showed only modest activity, several of their derivatives showed high order of antimalarial activity. Biphenyl-based compound 13f, the most active compound of the series, provided 100% and 80% protection to the infected mice at 12 mg/kg × 4 days and 6 mg/kg × 4 days, respectively. Compounds 12f, 13b, 13e, 13g, and 14f showed 100% protection at 12 mg/kg × 4 days, while compounds 12a-c, 14a, 14c-e, 14g, and 15a-c showed similar levels of protection at 24 mg/kg × 4 days. Clinically useful drug β-arteether provided 100% protection at 48 mg/kg × 4 days and 20% protection at 24 mg/kg × 4 days in this model.