(Z)-N-methoxy-1,2-bis[(1S,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]ethanimine

• 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: (Z)-N-methoxy-1,2-bis[(1S,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]ethanimine
• 化学式: C₃₃H₅₁NO₉
• 分子量: 605.769
• InChiKey: RMSQGHNEVGHPJO-LTMAHHBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  43
• 可旋转键数：
  4
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  95.4
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  artemisinin 在 吡啶 、 mercury(II) diacetate 、 二异丁基氢化铝 、 对甲苯磺酸 、 三乙胺 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 4.17h， 生成 (Z)-N-methoxy-1,2-bis[(1S,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]ethanimine 、
  参考文献：
  名称：

  Synthesis and Antimalarial Efficacy of Two-Carbon-Linked, Artemisinin-Derived Trioxane Dimers in Combination with Known Antimalarial Drugs

  摘要：

  Malaria continues to be a difficult disease to eradicate largely because of the widespread populations it affects and the resistance that malaria parasites have developed against once very potent therapies. The natural product artemisinin has been a boon for antimalarial chemotherapy, as artemisinin combination therapy (ACT) has become the first line of chemotherapy. Because the threat of resistance is always on the horizon, it is imperative to continually identify new treatments, comprising both advanced analogues of all antimalarial drugs, especially artemisinin, and the exploration of novel combinations, ideally with distinct mechanisms of action. Here we report for the first time the synthesis of a series of two-carbon-linked artemisinin-derived dimers, their unique structural features, and demonstration of their antimalarial efficacy via single oral dose administration in two 60-day survival studies of Plasmodium berghei infected mice. Several of the new endoperoxide chemical entities consistently demonstrated excellent antimalarial efficacy, and combinations with two non-peroxide antimalarial drugs have been studied.

  DOI：

  10.1021/jm400058j

文献信息

• [EN] TWO-CARBON LINKED ARTEMISININ-DERIVED TRIOXANE DIMERS<br/>[FR] DIMÈRES DE TRIOXANE DÉRIVÉS D'ARTÉMISININE LIÉS À DEUX ATOMES DE CARBONE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2014116642A1

  公开（公告）日：2014-07-31

  Two-carbon linked artemisinin-derived trioxane dimers and methods of their use for treating subjects infected with malaria or other parasitic infectious diseases including, but not limited to, toxoplasmic infection; subjects afflicted with psychiatric conditions associated with toxoplasmic infection; and subjects afflicted with cancer.

  两碳键合的青蒿素衍生三氧杂环二聚体及其用于治疗感染疟疾或其他寄生虫传染病的方法，包括但不限于弓形虫感染；患有与弓形虫感染相关的精神疾病的受试者；以及患有癌症的受试者。
• US9487538B2
  申请人：——

  公开号：US9487538B2

  公开（公告）日：2016-11-08
• Synthesis and Antimalarial Efficacy of Two-Carbon-Linked, Artemisinin-Derived Trioxane Dimers in Combination with Known Antimalarial Drugs
  作者：Bryan T. Mott、Abhai Tripathi、Maxime A. Siegler、Cathy D. Moore、David J. Sullivan、Gary H. Posner

  DOI：10.1021/jm400058j

  日期：2013.3.28

  Malaria continues to be a difficult disease to eradicate largely because of the widespread populations it affects and the resistance that malaria parasites have developed against once very potent therapies. The natural product artemisinin has been a boon for antimalarial chemotherapy, as artemisinin combination therapy (ACT) has become the first line of chemotherapy. Because the threat of resistance is always on the horizon, it is imperative to continually identify new treatments, comprising both advanced analogues of all antimalarial drugs, especially artemisinin, and the exploration of novel combinations, ideally with distinct mechanisms of action. Here we report for the first time the synthesis of a series of two-carbon-linked artemisinin-derived dimers, their unique structural features, and demonstration of their antimalarial efficacy via single oral dose administration in two 60-day survival studies of Plasmodium berghei infected mice. Several of the new endoperoxide chemical entities consistently demonstrated excellent antimalarial efficacy, and combinations with two non-peroxide antimalarial drugs have been studied.