(+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(3,5-bis-trifluoromethylphenyl)propyl)-12H-pyrano[4,3j]-1,2-benzoxepin-10(3H)-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(3,5-bis-trifluoromethylphenyl)propyl)-12H-pyrano[4,3j]-1,2-benzoxepin-10(3H)-one
• 英文别名: (1S,4S,5R,8S,9R,12S,13R)-9-[3-[3,5-bis(trifluoromethyl)phenyl]propyl]-1,5-dimethyl-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecan-10-one
• 化学式: C₂₅H₂₈F₆O₄
• 分子量: 506.485
• InChiKey: UJTPPDDBKHONDF-RMIJPSTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  青蒿素 在 palladium on activated charcoal 偶氮二异丁腈 、 氢气 、 三正丁基氢锡 、 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 苯 为溶剂， 反应 28.0h， 生成 (+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(3,5-bis-trifluoromethylphenyl)propyl)-12H-pyrano[4,3j]-1,2-benzoxepin-10(3H)-one
  参考文献：
  名称：

  Structure−Activity Relationships of the Antimalarial Agent Artemisinin. 8. Design, Synthesis, and CoMFA Studies toward the Development of Artemisinin-Based Drugs against Leishmaniasis and Malaria

  摘要：

  Artemisinin (1) and its analogues have been well studied for their antimalarial activity. Here we present the antimalarial activity of some novel C-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. Further, antileishmanial activity of more than 70 artemisinin derivatives against Leishmania donovani promastigotes is described for the first time. A comprehensive structure-activity relationship study using CoMFA is discussed. These analogues exhibited leishmanicidal activity in micromolar concentrations, and the overall activity profile appears to be similar to that against malaria. Substitution at the C-9beta position was shown to improve the activity in both cases. The 10-deoxo derivatives showed better activity compared to the corresponding lactones. In general, compounds with C-9alpha substitution exhibited lower antimalarial as well as antileishmanial activities compared to the corresponding C-9beta analogues. The importance of the peroxide group for the observed activity of these analogues against leishmania was evident from the fact that 1-deoxyartemisinin analogues did not exhibit antileishmanial activity. The study suggests the possibility of developing artemisinin analogues as potential drug candidates against both malaria and leishmaniasis.

  DOI：

  10.1021/jm030181q

文献信息

• Structure−Activity Relationships of the Antimalarial Agent Artemisinin. 8. Design, Synthesis, and CoMFA Studies toward the Development of Artemisinin-Based Drugs against Leishmaniasis and Malaria
  作者：Mitchell A. Avery、Kannoth M. Muraleedharan、Prashant V. Desai、Achintya K. Bandyopadhyaya、Marise M. Furtado、Babu L. Tekwani

  DOI：10.1021/jm030181q

  日期：2003.9.1

  Artemisinin (1) and its analogues have been well studied for their antimalarial activity. Here we present the antimalarial activity of some novel C-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. Further, antileishmanial activity of more than 70 artemisinin derivatives against Leishmania donovani promastigotes is described for the first time. A comprehensive structure-activity relationship study using CoMFA is discussed. These analogues exhibited leishmanicidal activity in micromolar concentrations, and the overall activity profile appears to be similar to that against malaria. Substitution at the C-9beta position was shown to improve the activity in both cases. The 10-deoxo derivatives showed better activity compared to the corresponding lactones. In general, compounds with C-9alpha substitution exhibited lower antimalarial as well as antileishmanial activities compared to the corresponding C-9beta analogues. The importance of the peroxide group for the observed activity of these analogues against leishmania was evident from the fact that 1-deoxyartemisinin analogues did not exhibit antileishmanial activity. The study suggests the possibility of developing artemisinin analogues as potential drug candidates against both malaria and leishmaniasis.