adamantane-2-spiro-3'-1',2',4'-trioxa-8'-azaspiro[4,5]decane | 476629-38-6

• 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'-1',2',4'-trioxa-8'-azaspiro[4,5]decane
• CAS: 476629-38-6
• 化学式: C₁₅H₂₃NO₃
• 分子量: 265.353
• InChiKey: VTPZCADQIJNCMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 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：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  adamantane-2-spiro-3'-1',2',4'-trioxa-8'-azaspiro[4,5]decane 、 乙基乙烯基砜 在 三乙胺 作用下， 以72%的产率得到
  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：

  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

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。
• 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
• US7947701B2
  申请人：——

  公开号：US7947701B2

  公开（公告）日：2011-05-24
• 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.
• Antimalarial activity of N-alkyl amine, carboxamide, sulfonamide, and urea derivatives of a dispiro-1,2,4-trioxolane piperidine
  作者：Maniyan Padmanilayam、Bernard Scorneaux、Yuxiang Dong、Jacques Chollet、Hugues Matile、Susan A. Charman、Darren J. Creek、William N. Charman、Josefina Santo Tomas、Christian Scheurer、Sergio Wittlin、Reto Brun、Jonathan L. Vennerstrom

  DOI：10.1016/j.bmcl.2006.08.046

  日期：2006.11

  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.