(1R,4S,5R,8S,9R,12R,13R)-9-[3-[4-(dimethylamino)phenyl]propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol | 613233-77-5

• 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,8S,9R,12R,13R)-9-[3-[4-(dimethylamino)phenyl]propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol
• CAS: 613233-77-5
• 化学式: C₂₅H₃₇NO₅
• 分子量: 431.572
• InChiKey: QSTKMACDGOKHLW-SNPPBQTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,4S,5R,8S,9R,12R,13R)-9-[3-[4-(dimethylamino)phenyl]propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol 在 三乙基硅烷 、 三氟化硼乙醚 、 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 7.17h， 以35%的产率得到(+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(p-N,N-dimethylaminophenyl)propyl)-12H-pyrano[4,3j]-1,2-benzodioxepin-10(3H)-one
  参考文献：
  名称：

  [EN] ARTEMISININ-BASED PEROXIDE COMPOUNDS AS BROAD SPECTRUM ANTI-INFECTIVE AGENTS
  [FR] COMPOSES DE PEROXYDE A BASE D'ARTEMISININE TENANT LIEU D'AGENTS ANTI-INFECTIEUX A LARGE SPECTRE

  摘要：

  本文描述了合成、生物测定结果以及新的C-9和C-10取代青蒿素衍生物的用途，这些衍生物具有易于功能化的基团，通过碳链或杂原子连接到青蒿素骨架上。同时还展示了这类化合物在广谱抗寄生虫活性方面的表现。其中一些类似物具有明显的细胞毒性，专门用于治疗癌症性疾病。

  公开号：

  WO2003095444A1
• 作为产物：
  描述：

  青蒿素 在 偶氮二异丁腈 、 三正丁基氢锡 、 二异丁基氢化铝 、 碳酸氢钠 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 苯 为溶剂， 反应 11.0h， 生成 (1R,4S,5R,8S,9R,12R,13R)-9-[3-[4-(dimethylamino)phenyl]propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol
  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.
• [EN] ARTEMISININ-BASED PEROXIDE COMPOUNDS AS BROAD SPECTRUM ANTI-INFECTIVE AGENTS<br/>[FR] COMPOSES DE PEROXYDE A BASE D'ARTEMISININE TENANT LIEU D'AGENTS ANTI-INFECTIEUX A LARGE SPECTRE
  申请人：UNIV MISSISSIPI

  公开号：WO2003095444A1

  公开（公告）日：2003-11-20

  Described herein is the synthesis, bioassay results and utility of new C-9 and C-10 substituted artemisinin derivatives with easily functionalizable groups attached to the artemisinin skeleton through carbon chain or heteroatoms. Described also is the demonstration of this class of compounds for their broad-spectrum anti-parasitic activity. Certain of these analogs possess noticeable cytotoxicity deliberately focused on treatment of cancerous diseases.

  本文描述了合成、生物测定结果以及新的C-9和C-10取代青蒿素衍生物的用途，这些衍生物具有易于功能化的基团，通过碳链或杂原子连接到青蒿素骨架上。同时还展示了这类化合物在广谱抗寄生虫活性方面的表现。其中一些类似物具有明显的细胞毒性，专门用于治疗癌症性疾病。