10β-[2-(4-fluorobenzyloxy)ethyl]deoxoartemisinin

• 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: 10β-[2-(4-fluorobenzyloxy)ethyl]deoxoartemisinin
• 英文别名: (1R,4S,5R,8S,9R,10R,12R,13R)-10-[2-[(4-fluorophenyl)methoxy]ethyl]-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
• 化学式: C₂₄H₃₃FO₅
• 分子量: 420.521
• InChiKey: AAAIJRIEGUHNCI-SBTIGIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氟溴苄 、 10β-(2-hydroxyethyl)deoxoartemisinin 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.92h， 以42%的产率得到10β-[2-(4-fluorobenzyloxy)ethyl]deoxoartemisinin
  参考文献：
  名称：

  Novel, Potent, Semisynthetic Antimalarial Carba Analogues of the First-Generation 1,2,4-Trioxane Artemether

  摘要：

  Ten novel, second-generation, fluorinated ether and ester analogues of the potent first-generation analogues artemether (4a) and arteether (4b) have been designed and synthesized. All of the compounds demonstrate high antimalarial potency in vitro against the chloroquine-sensitive HB3 and -resistant K1 strains of Plasmodium falciparum. The most potent derivative 8 was 15 times more potent than artemisinin (2) against the HB3 strain of P. falciparum. In vivo, versus Plasmodium berghei in the mouse, selected derivatives were generally less potent than dihydroartemisinin with ED50 values of between 5 and 8 mg/kg. On the basis of the products obtained from the in vitro biomimetic Fe(II)-mediated decomposition of 8, the radical mediator of biological activity of this series may be different from that of the parent drug, artemisinin (2).

  DOI：

  10.1021/jm9903545

文献信息

• Novel, Potent, Semisynthetic Antimalarial Carba Analogues of the First-Generation 1,2,4-Trioxane Artemether
  作者：Paul M. O'Neill、Natalie L. Searle、Ka-Wing Kan、Richard C. Storr、James L. Maggs、Stephen A. Ward、Kaylene Raynes、B. Kevin Park

  DOI：10.1021/jm9903545

  日期：1999.12.1

  Ten novel, second-generation, fluorinated ether and ester analogues of the potent first-generation analogues artemether (4a) and arteether (4b) have been designed and synthesized. All of the compounds demonstrate high antimalarial potency in vitro against the chloroquine-sensitive HB3 and -resistant K1 strains of Plasmodium falciparum. The most potent derivative 8 was 15 times more potent than artemisinin (2) against the HB3 strain of P. falciparum. In vivo, versus Plasmodium berghei in the mouse, selected derivatives were generally less potent than dihydroartemisinin with ED50 values of between 5 and 8 mg/kg. On the basis of the products obtained from the in vitro biomimetic Fe(II)-mediated decomposition of 8, the radical mediator of biological activity of this series may be different from that of the parent drug, artemisinin (2).