O²-2-[(3-carboxy-1-oxopropoxy)methoxy]-1-(1-pyrrolidinyl)-diazen-1-ium-1,2-diolate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: O²-2-[(3-carboxy-1-oxopropoxy)methoxy]-1-(1-pyrrolidinyl)-diazen-1-ium-1,2-diolate
• 化学式: C₉H₁₅N₃O₆
• 分子量: 261.235
• InChiKey: GFIUHBKRHVMXBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.26
• 重原子数：
  18.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  114.5
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  O²-2-[(3-carboxy-1-oxopropoxy)methoxy]-1-(1-pyrrolidinyl)-diazen-1-ium-1,2-diolate 、 dihydroartemisinin 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 O²-2-[[4-[[decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-yl]oxy]-1,4-dioxobutoxy]methoxy]-1-(1-pyrrolidinyl)-diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria

  摘要：

  Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA., comparable to artesunate and artemether. Hybrid 10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6% compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria.

  DOI：

  10.1021/acs.jmedchem.5b01036
• 作为产物：
  描述：

  O²-chloromethyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate 在 caesium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 苯酚 为溶剂， 反应 2.08h， 生成 O²-2-[(3-carboxy-1-oxopropoxy)methoxy]-1-(1-pyrrolidinyl)-diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria

  摘要：

  Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA., comparable to artesunate and artemether. Hybrid 10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6% compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria.

  DOI：

  10.1021/acs.jmedchem.5b01036

文献信息

• NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria
  作者：Massimo Bertinaria、Pamela Orjuela-Sanchez、Elisabetta Marini、Stefano Guglielmo、Anthony Hofer、Yuri C. Martins、Graziela M. Zanini、John A. Frangos、Alberto Gasco、Roberta Fruttero、Leonardo J. M. Carvalho

  DOI：10.1021/acs.jmedchem.5b01036

  日期：2015.10.8

  Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA., comparable to artesunate and artemether. Hybrid 10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6% compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria.