4-(trifluoromethyl)-N-((3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trimethyl-10-oxodecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]-isoquinolin-11(12H)-yl)benzamide | 1086409-91-7

• 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: 4-(trifluoromethyl)-N-((3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trimethyl-10-oxodecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]-isoquinolin-11(12H)-yl)benzamide
• 英文别名: 4-(trifluoromethyl)-N-[(1R,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-10-oxo-14,15,16-trioxa-11-azatetracyclo[10.3.1.04,13.08,13]hexadecan-11-yl]benzamide
• CAS: 1086409-91-7
• 化学式: C₂₃H₂₇F₃N₂O₅
• 分子量: 468.473
• InChiKey: KOJCQAJKICCUPY-NIUNIBNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  青蒿素 在 一水合肼 、 三乙胺 作用下， 以 甲醇 、 氯仿 、 苯 为溶剂， 反应 15.08h， 生成 4-(trifluoromethyl)-N-((3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trimethyl-10-oxodecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]-isoquinolin-11(12H)-yl)benzamide
  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

• Amino- and Hydroxy-Functionalized 11-Azaartemisinins and Their Derivatives
  作者：Ajit Shankar Singh、Ved Prakash Verma、Mohammad Hassam、Naikade Niraj Krishna、Sunil K. Puri、Chandan Singh

  DOI：10.1021/ol802238d

  日期：2008.12.4

  conversion of artemisinin 1 into three new amino- and hydroxy-functionalized 11-aza prototypes 9, 11, and 12 has been achieved on a multigram scale by reaction with hydrazine, hydroxylamine, and 2-amino ethanol, respectively. Of these, 9 has been further diversified into a wide range of derivatives including imines, amines, amides, and linker based dimers. Prototypes 11 and 12 have been converted into the

  通过分别与肼、羟胺和 2-氨基乙醇反应，青蒿素 1 有效转化为三个新的氨基和羟基官能化的 11-氮杂原型 9、11 和 12。其中 9 种已进一步多样化为各种衍生物，包括亚胺、胺、酰胺和基于接头的二聚体。原型 11 和 12 已以高产率转化为相应的醚。这些化合物中的一些已通过口服途径在小鼠体内显示出对耐多药疟疾的高活性。
• 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.