3-Oxo-7,14,15-trioxadispiro[5.1.5.2]pentadecane | 189824-44-0

• 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: 3-Oxo-7,14,15-trioxadispiro[5.1.5.2]pentadecane
• 英文别名: 7,14,15-Trioxadispiro[5.1.5.2]pentadecan-3-one；7,14,15-trioxadispiro[5.1.58.26]pentadecan-11-one
• CAS: 189824-44-0
• 化学式: C₁₂H₁₈O₄
• 分子量: 226.273
• InChiKey: GEWIRNPCVKWKGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  环己酮O-甲基肟 、 1,4-环己二酮 在 ozone 作用下， 以 二氯甲烷 、 Petroleum ether 、 正戊烷 为溶剂， 生成 3-Oxo-7,14,15-trioxadispiro[5.1.5.2]pentadecane
  参考文献：
  名称：

  Spiro and dispiro 1,2,4-trioxolane antimalarials

  摘要：

  描述了一种利用螺环或二螺环1,2,4-三噁烷治疗疟疾的方法和手段。首选的1,2,4-三噁烷包括在三噁烷基团的一侧具有螺环戊烷基团，并在三噁烷基团的另一侧具有螺环环己基或螺环哌啶基团，其中螺环环己基环在4-位功能化或取代，或者螺环哌啶基团在氮原子处功能化或取代。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。

  公开号：

  US06486199B1

文献信息

• Diozonides from coozonolyses of suitable O-methyl oximes and ketones
  作者：Karl Griesbaum、Xuejun Liu、Yuxiang Dong

  DOI：10.1016/s0040-4020(97)00260-3

  日期：1997.4

  ketones 5a - c in the presence of 1,4-cyclohexanedione (6) and ozonolyses of the O-methylated dioxime 8 of 1,4-cyclohexanedione in the presence of cycloketones 7a - c afforded the corresponding diozonides 11. Ozonolysis of the O-methyl oxime of acetone gave diozonide 18 in the presence of 6 and diozonide 21 in the presence of butanedione. Ozonolysis of the O-methyl oxime of cyclohexanone in the presence

  在1,4-环己二酮（6）存在下环酮5a-c的O-甲基肟的臭氧分解反应和在环酮7a-c的存在下1,4-环己烷二酮的O-甲基化二肟8的臭氧分解反应提供了如下产物。相应的重氮化合物11。丙酮的O-甲基肟的臭氧分解在6和6的存在下产生了重氮化合物18，在丁二酮的存在下产生了重氮化合物21。在丁烷二酮的存在下，将环己酮的O-甲基肟进行臭氧分解，得到重氮酮22。此外，迄今未知类型的双螺旋臭氧化物的代表12具有内酰胺环系统的已从8和7的臭氧分解物中获得。
• [EN] 1,2,4-TRIOXOLANE ANTIMALARIALS<br/>[FR] ANTIPALUDIQUES A BASE DE 1,2,4-TRIOXOLANE
  申请人：MEDICINES MALARIA VENTURE MMV

  公开号：WO2003000676A1

  公开（公告）日：2003-01-03

  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.

  本发明涉及使用螺环或双螺环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螺环戊烷基团位于三噁烷基团的一侧，以及一个螺环己基位于三噁烷基团的另一侧，其中螺环己环在4位处优选被取代。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，并且对疟原虫具有很强的杀灭作用。
• 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.
• 1,2,4-TRIOXOLANE ANTIMALARIALS
  申请人：Medicines for Malaria Venture

  公开号：EP1414813A1

  公开（公告）日：2004-05-06
• US6486199B1
  申请人：——

  公开号：US6486199B1

  公开（公告）日：2002-11-26