adamantane-2-spiro-3'-8'-tert-butoxycarbonyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane | 476373-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: adamantane-2-spiro-3'-8'-tert-butoxycarbonyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane
• 英文别名: PA 1016
• CAS: 476373-25-8
• 化学式: C₂₀H₃₁NO₅
• 分子量: 365.47
• InChiKey: VMEPRKURSLAPDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  adamantane-2-spiro-3'-8'-tert-butoxycarbonyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane 以34%的产率得到adamantane-2-spiro-3'-1',2',4'-trioxa-8'-azaspiro[4,5]decane
  参考文献：
  名称：

  Antimalarial activity of N-alkyl amine, carboxamide, sulfonamide, and urea derivatives of a dispiro-1,2,4-trioxolane piperidine

  摘要：

  With an aim to identify a dispiro-1,2,4-trioxolane with high oral activity and good physicochemical properties, 27 derivatives of an achiral piperidine trioxolane were synthesized; most were potent antimalarial peroxides with IC(50)s ranging from 0.20 to 7.0 ng/mL. The oral efficacies of two of these were superior to artesunate and comparable to artemether. The attractive chemical simplicity of these compounds is balanced only by an apparent metabolic susceptibility. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.046
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 、 adamantan-2-one O-methyloxime 在 臭氧 作用下， 生成 adamantane-2-spiro-3'-8'-tert-butoxycarbonyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane
  参考文献：
  名称：

  Antimalarial activity of N-alkyl amine, carboxamide, sulfonamide, and urea derivatives of a dispiro-1,2,4-trioxolane piperidine

  摘要：

  With an aim to identify a dispiro-1,2,4-trioxolane with high oral activity and good physicochemical properties, 27 derivatives of an achiral piperidine trioxolane were synthesized; most were potent antimalarial peroxides with IC(50)s ranging from 0.20 to 7.0 ng/mL. The oral efficacies of two of these were superior to artesunate and comparable to artemether. The attractive chemical simplicity of these compounds is balanced only by an apparent metabolic susceptibility. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.046

文献信息

• Dual molecules containing peroxy derivative, the synthesis and therapeutic applications thereof
  申请人：Cazelles Jerome

  公开号：US20070021423A1

  公开（公告）日：2007-01-25

  The invention relates to dual molecule compounds containing a peroxide derivative, to processes for the synthesis of such compounds, to pharmaceutical compositions comprising such compounds, and to methods of treatment and prevention of malaria comprising administering such compounds and such pharmaceutical compositions.

  这项发明涉及含有过氧化物衍生物的双分子化合物，涉及合成这种化合物的方法，涉及包括这种化合物的药物组合物，以及涉及通过给予这种化合物和这种药物组合物来治疗和预防疟疾的方法。
• Cyclic peroxides as prodrugs for selective delivery of agents
  申请人：The Regents of the University of California

  公开号：US10287312B2

  公开（公告）日：2019-05-14

  Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5]decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier.

  本文特别公开了原药组合物以及使用原药组合物治疗和检测疾病的方法。具体地说，本文公开了一种具有螺融合 1，2，4-三氧环和哌啶环的式 (I) 化合物，即 1，2，4-三氧杂-8-氮杂螺[4.5]癸烷。还公开了一种药物组合物，其中含有该化合物和一种药学上可接受的载体。
• Structure−Activity Relationship of an Ozonide Carboxylic Acid (OZ78) against<i>Fasciola hepatica</i>
  作者：Qingjie Zhao、Mireille Vargas、Yuxiang Dong、Lin Zhou、Xiaofang Wang、Kamaraj Sriraghavan、Jennifer Keiser、Jonathan L. Vennerstrom

  DOI：10.1021/jm100226t

  日期：2010.5.27

  In this paper, we describe the SAR of ozonide carboxylic acid OZ78 (1) as the first part of our search for a trematocidal synthetic peroxide drug development candidate. We found that relatively small structural changes to 1 resulted most commonly in loss of activity against Fasciola hepatica in vivo. A spiro-adamantane substructure and acidic functional group (or ester prodrug) were required for activity. Of 26 new compounds administered at single 100 mg/kg oral doses to F. hepatica infected rats, 8 had statistically significant worm burden reductions, 7 were partially curative, and 1 (acylsulfonamide 6) was completely curative and comparable to 1 in flukicidal efficacy. This study also showed that the activity of 1 is peroxide-bond-dependent, suggesting that its flukicidal efficacy depends upon hemoglobin digestion in F. hepatica.
• MOLECULES DUALES CONTENANT UN DERIVE PEROXYDIQUE, LEUR SYNTHESE ET LEURS APPLICATIONS THERAPEUTIQUES
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：EP1687312B1

  公开（公告）日：2010-07-14
• CYCLIC PEROXIDES AS PRODRUGS FOR SELECTIVE DELIVERY OF AGENTS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20160362439A1

  公开（公告）日：2016-12-15

  Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5]decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier.