OZ-03 | 55975-26-3

• 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: OZ-03
• 英文别名: Ozonid des Cyclohexylidenadamantans；Adamantane-2-spiro-3'-1',2',4'-trioxaspiro[4.5]decane
• CAS: 55975-26-3
• 化学式: C₁₆H₂₄O₃
• 分子量: 264.365
• InChiKey: VZOUNANDPPKHBS-UHFFFAOYSA-N

物化性质

• 沸点：
  368.9±31.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  6.0
• 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

• 作为反应物：
  描述：

  OZ-03 在 iron(II) bromide 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以64%的产率得到4-噁高金刚烷-5-酮
  参考文献：
  名称：

  原型 Dispiro-1,2,4-trioxane 类似物 Dispiro-1,2,4-trioxolane：在与铁反应途径背景下青蒿素的机理比较 (II)

  摘要：

  青蒿素 ( 1 )的 1,2,4-三恶烷杂环的单电子还原形成一级和二级碳中心自由基。的复杂结构1本身不适合于对影响形成和这些碳中心自由基的后续反应的电子和空间影响的满意的清扫。为了帮助区分这些影响，我们表征了非手性双螺-1,2,4-三氧戊环4和双螺-1,2,4-三氧杂环戊烷5 - 7与溴化亚铁和 4-氧代-TEMPO 的反应。我们的结果表明了铁（II）的攻击上的nonketal过氧化物氧原子小的偏好1。对于4，但不是对于5和6，Fe(II) 对受阻较小的过氧化物键氧原子的攻击有强烈的偏好。螺金刚烷在五元三氧杂环戊烷中提供的空间位阻显然比相应的六元三氧杂环己烷大得多。与1 , 5 - 7不同的是，通过熵有利的 β 断裂途径形成相对稳定的 α-氧杂碳中心自由基。这些数据表明，一级或二级碳中心自由基的形成是1和合成过氧化物的抗疟活性的必要但不充分的标准。

  DOI：

  10.1021/jo050385+
• 作为产物：
  描述：

  环己酮 、 adamantan-2-one O-methyloxime 在 臭氧 作用下， 以 正戊烷 为溶剂， 反应 0.05h， 以52%的产率得到OZ-03
  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

• [EN] TRIOXOLANE AGENTS<br/>[FR] AGENTS TRIOXOLANE
  申请人：UNIV CALIFORNIA

  公开号：WO2019005977A1

  公开（公告）日：2019-01-03

  Disclosed herein, inter alia, are trioxolane compounds and methods of using the same for treatment and detection of diseases.

  本文披露了三氧杂环戊烷化合物及其在治疗和检测疾病中的应用方法。
• SPIRO AND DISPIRO 1,2,4-TRIOXOLANE ANTIMALARIALS
  申请人：VENNERSTROM JONATHAN L.

  公开号：US20080125441A1

  公开（公告）日：2008-05-29

  A means and method for treating malaria, schistosomiasis, and cancer using a Spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl on the other side of the trioxolane group, whereby the spirocyclohexyl ring is preferably substituted at the 4-position. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites.

  本发明涉及使用Spiro或dispiro 1,2,4-三噁烷治疗疟疾、血吸虫病和癌症的方法和手段。首选的1,2,4-三噁烷包括一个spiroadamantane基团位于三噁烷基团的一侧，而spirocyclohexyl位于三噁烷基团的另一侧，其中spirocyclohexyl环在4位处被取代。与青蒿素半合成衍生物相比，本发明化合物结构简单，易于合成，无毒，并且对疟原虫具有强效作用。
• DISPIRO 1,2,4-TRIOXOLANE ANTIMALARIALS
  申请人：VENNERSTROM JONATHAN L.

  公开号：US20080125411A1

  公开（公告）日：2008-05-29

  A means and method for treating malaria, schistosomiasis, and cancer using a spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl on the other side of the trioxolane group. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites. The compounds of the invention unexpectedly provide a single-dose cure for malaria, as well as prophylactic activity against the same. The compounds are also active against schistosomiasis and cancer.

  本发明提供了一种治疗疟疾、血吸虫病和癌症的方法和手段，使用螺环或二螺环1,2,4-三噁烷酮。首选的1,2,4-三噁烷酮包括一个螺环戊烷基团在三噁烷基团的一侧，以及一个螺环己基在三噁烷基团的另一侧。与青蒿素半合成衍生物相比，本发明的化合物结构简单，易于合成，无毒，并且对疟原虫具有强效作用。该发明的化合物意外地提供了一次性治愈疟疾的方法，以及对其的预防活性。该化合物也对血吸虫病和癌症具有活性。
• Prodrug and Fluoregenic Compositions and Methods for Using the Same
  申请人：Renslo Adam

  公开号：US20110190291A1

  公开（公告）日：2011-08-04

  Methods and compositions for treating disease caused by increased iron levels are disclosed Fluoregenic compounds and methods of using the same are also described.

  本发明揭示了用于治疗由铁过量引起的疾病的方法和组合物。还描述了荧光化合物及其使用方法。
• Trioxolane agents
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US11072594B2

  公开（公告）日：2021-07-27

  Disclosed herein, inter alia, are trioxolane compounds and methods of using the same for treatment and detection of diseases.

  本文特别披露了三氧环化合物以及使用三氧环化合物治疗和检测疾病的方法。