Ozonid des Bis-adamantyliden | 55975-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三氧戊环
• 英文名称: Ozonid des Bis-adamantyliden
• CAS: 55975-25-2
• 化学式: C₂₀H₂₈O₃
• 分子量: 316.441
• InChiKey: NUMLGZYGDCSHDV-UHFFFAOYSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  金刚烷酮 、 adamantan-2-one O-methyloxime 在 臭氧 作用下， 以 正戊烷 为溶剂， 反应 0.05h， 以40%的产率得到Ozonid des Bis-adamantyliden
  参考文献：
  名称：

  Spiro and Dispiro-1,2,4-trioxolanes as Antimalarial Peroxides:  Charting a Workable Structure−Activity Relationship Using Simple Prototypes

  摘要：

  This paper describes the discovery of synthetic 1,2,4-trioxolane antimalarials and how we established a workable structure-activity relationship in the context of physicochemical, biopharmaceutical, and toxicological profiling. An achiral dispiro-1,2,4-trioxolane (3) in which the trioxolane is flanked by a spiroadamantane and spirocyclohexane was rapidly identified as a lead compound. Nonperoxidic 1,3-dioxolane isosteres of 3 were inactive as were trioxolanes without the spiroadamantane. The trioxolanes were substantially less effective in a standard oral suspension formulation compared to a solubilizing formulation and were more active when administered subcutaneously than orally, both of which suggest substantial biopharmaceutical liabilities. Nonetheless, despite their limited oral bioavailability, the more lipophilic trioxolanes generally had better oral activity than their more polar counterparts. In pharmacokinetic experiments, four trioxolanes had high plasma clearance values, suggesting a potential metabolic instability. The toxicological profiles of two trioxolanes were comparable to that of artesunate.

  DOI：

  10.1021/jm049040u

文献信息

• Spiro and Dispiro-1,2,4-trioxolanes as Antimalarial Peroxides:  Charting a Workable Structure−Activity Relationship Using Simple Prototypes
  作者：Yuxiang Dong、Jacques Chollet、Hugues Matile、Susan A. Charman、Francis C. K. Chiu、William N. Charman、Bernard Scorneaux、Heinrich Urwyler、Josefina Santo Tomas、Christian Scheurer、Christopher Snyder、Arnulf Dorn、Xiaofang Wang、Jean M. Karle、Yuanqing Tang、Sergio Wittlin、Reto Brun、Jonathan L. Vennerstrom

  DOI：10.1021/jm049040u

  日期：2005.7.1

  This paper describes the discovery of synthetic 1,2,4-trioxolane antimalarials and how we established a workable structure-activity relationship in the context of physicochemical, biopharmaceutical, and toxicological profiling. An achiral dispiro-1,2,4-trioxolane (3) in which the trioxolane is flanked by a spiroadamantane and spirocyclohexane was rapidly identified as a lead compound. Nonperoxidic 1,3-dioxolane isosteres of 3 were inactive as were trioxolanes without the spiroadamantane. The trioxolanes were substantially less effective in a standard oral suspension formulation compared to a solubilizing formulation and were more active when administered subcutaneously than orally, both of which suggest substantial biopharmaceutical liabilities. Nonetheless, despite their limited oral bioavailability, the more lipophilic trioxolanes generally had better oral activity than their more polar counterparts. In pharmacokinetic experiments, four trioxolanes had high plasma clearance values, suggesting a potential metabolic instability. The toxicological profiles of two trioxolanes were comparable to that of artesunate.