(1R,4S,5R,8R,9S,10S,12R,13R)-9-bromo-N-(3-fluorophenyl)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-amine | 127997-42-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1R,4S,5R,8R,9S,10S,12R,13R)-9-bromo-N-(3-fluorophenyl)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-amine
• CAS: 127997-42-6
• 化学式: C₂₁H₂₇BrFNO₄
• 分子量: 456.352
• InChiKey: DFCFMQCTNPNDEL-AWBOJGQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  dihydroartemisinin 在 三氟化硼乙醚 、 溴 作用下， 以 四氯化碳 、 乙醚 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 (1R,4S,5R,8R,9S,10S,12R,13R)-9-bromo-N-(3-fluorophenyl)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-amine
  参考文献：
  名称：

  Antimalarial activity of new water-soluble dihydroartemisinin derivatives. 3. Aromatic amine analogs

  摘要：

  A series of artemisinin (1) derivatives containing bromo and heterocyclic or aromatic amine functions was prepared in the search for analogues with good water solubility and high antimalarial activity. Treatment of dihydroartemisinin (2a) with boron trifluoride etherate at room temperature gave the key intermediate, 9,10-dehydrodihydroartemisinin (3), which, on reaction with bromine, gave the dibromide 4. The latter was condensed with amines in anhydrous CH2Cl2 at less than -10 degrees C to give the desired products in 25-55% yield. The new derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Compound 6b, 3-fluoroaniline derivative, was the most active of the series, with the IC50 less than or equal to 0.16 ng/mL, making it several fold more potent than 1. However, no significant in vivo antimalarial activity against Plasmodium berghei was observed in any of the new compounds tested.

  DOI：

  10.1021/jm00171a041

文献信息

• LIN, AI J.;LI, LIANG-QUAN;KLAYMAN, DANIEL L.;GEORGE, CLIFFORD F.;FLIPEEN-+, J. MED. CHEM., 33,(1990) N, C. 2610-2614
  作者：LIN, AI J.、LI, LIANG-QUAN、KLAYMAN, DANIEL L.、GEORGE, CLIFFORD F.、FLIPEEN-+

  DOI：——

  日期：——
• Antimalarial activity of new water-soluble dihydroartemisinin derivatives. 3. Aromatic amine analogs
  作者：Ai J. Lin、Liang Quan Li、Daniel L. Klayman、Clifford F. George、Judith L. Flippen-Anderson

  DOI：10.1021/jm00171a041

  日期：1990.9

  A series of artemisinin (1) derivatives containing bromo and heterocyclic or aromatic amine functions was prepared in the search for analogues with good water solubility and high antimalarial activity. Treatment of dihydroartemisinin (2a) with boron trifluoride etherate at room temperature gave the key intermediate, 9,10-dehydrodihydroartemisinin (3), which, on reaction with bromine, gave the dibromide 4. The latter was condensed with amines in anhydrous CH2Cl2 at less than -10 degrees C to give the desired products in 25-55% yield. The new derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Compound 6b, 3-fluoroaniline derivative, was the most active of the series, with the IC50 less than or equal to 0.16 ng/mL, making it several fold more potent than 1. However, no significant in vivo antimalarial activity against Plasmodium berghei was observed in any of the new compounds tested.