adamantane-2-spiro-3'-8'-carboxymethyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane sodium salt | 1227734-41-9

• 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'-carboxymethyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane sodium salt
• CAS: 1227734-41-9
• 化学式: C₁₇H₂₄NO₅*Na
• 分子量: 345.371
• InChiKey: YDYVVPRTLUFMQT-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.34
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  adamantane-2-spiro-3'-8'-ethoxycarbonylmethyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以84%的产率得到adamantane-2-spiro-3'-8'-carboxymethyl-1',2',4'-trioxa-8'-azaspiro[4.5]decane sodium salt
  参考文献：
  名称：

  Structure−Activity Relationship of an Ozonide Carboxylic Acid (OZ78) againstFasciola hepatica

  摘要：

  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.

  DOI：

  10.1021/jm100226t

文献信息

• 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.