adamantane-2-spiro-3'-8'-carboxymethyl-1',2',4'-trioxaspiro[4.5]decane | 476373-64-5

• 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: adamantane-2-spiro-3'-8'-carboxymethyl-1',2',4'-trioxaspiro[4.5]decane
• 英文别名: (1s, 4s)-dispiro[cyclohexane-1,3'-[1,2,4]trioxolane-5',2"-tricyclo[3.3.1.13,7]decan]-4-ylacetic acid
• CAS: 476373-64-5
• 化学式: C₁₈H₂₆O₅
• 分子量: 322.401
• InChiKey: ODKGGAKOCGCWDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 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：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  adamantane-2-spiro-3'-8'-carboxymethyl-1',2',4'-trioxaspiro[4.5]decane 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  铁载体和臭氧类化合物的酰胺和酯偶联物的合成和抗疟活性

  摘要：

  尽管治疗疟疾的化疗干预措施取得了进展，但仍需要开发新的抗疟药。先前的研究表明，氯喹与铁螯合剂去铁胺 （DFO） 等抗氧化剂的共同给药可防止脑疟疾替代模型中持续性认知损伤的发展。本文描述的工作报告了天然（铁载体）和人造铁螯合剂（即 DFO、铁蛋白和 ICL-670）与抗疟 1,2,4-三氧代戊烷（臭氧）的共价偶联物的合成和抗疟疾活性。所有合成的偶联物对恶性疟原虫耐药和药物敏感菌株的体外培养物具有有效的抗疟活性。本文描述的工作为未来开发铁螯合剂和抗疟化疗药物的共价组合治疗脑疟疾提供了基础。  图形摘要

  DOI：

  10.1007/s10534-022-00375-8
• 作为产物：
  描述：

  2-(4-氧代环己基)乙酸 、 2-hydroxy-2-(hydroxymethyl)adamantane 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以79%的产率得到adamantane-2-spiro-3'-8'-carboxymethyl-1',2',4'-trioxaspiro[4.5]decane
  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

• PROCESS FOR THE PREPARATION OF DISPIRO 1,2,4-TRIOXOLANE ANTIMALARIALS (OZ277)
  申请人：Yadav Gyan Chand

  公开号：US20110124886A1

  公开（公告）日：2011-05-26

  This invention relates to an improved process for the preparation of a compound of Formula (I), salts of the free base cis-adamantane-2-spiro-3′-8′-[[[(2′-amino-2′-methyl propyl)amino]carbonyl]methyl]-1′,2′,4′-trioxaspiro[4.5]decane wherein X can be an anion.

  本发明涉及一种改进的制备公式(I)化合物的过程，其中X可以是阴离子的自由基盐cis-金刚烷-2-螺-3'-8'-[[[(2'-氨基-2'-甲基丙基)氨基]羰基]甲基]-1'，2'，4'-三氧杂螺[4.5]癸烷。
• Process for the preparation of dispiro 1,2,4-trioxolane antimalarials (OZ277)
  申请人：Yadav Gyan Chand

  公开号：US08569519B2

  公开（公告）日：2013-10-29

  This invention relates to an improved process for the preparation of a compound of Formula (I), salts of the free base cis-adamantane-2-spiro-3′-8′-[[[(2′-amino-2′-methyl propyl)amino]carbonyl]methyl]-1′,2′,4′-trioxaspiro[4.5]decane wherein X can be an anion.

  本发明涉及一种改进的制备式（I）化合物的过程，其自由基盘cis-金刚烷-2-螺-3'-8'-[[[(2'-氨基-2'-甲基丙基)氨基]羰基]甲基]-1'，2'，4'-三氧杂螺[4.5]癸烷的盐，其中X可以是负离子。
• The Structure−Activity Relationship of the Antimalarial Ozonide Arterolane (OZ277)
  作者：Yuxiang Dong、Sergio Wittlin、Kamaraj Sriraghavan、Jacques Chollet、Susan A. Charman、William N. Charman、Christian Scheurer、Heinrich Urwyler、Josefina Santo Tomas、Christopher Snyder、Darren J. Creek、Julia Morizzi、Maria Koltun、Hugues Matile、Xiaofang Wang、Maniyan Padmanilayam、Yuanqing Tang、Arnulf Dorn、Reto Brun、Jonathan L. Vennerstrom

  DOI：10.1021/jm901473s

  日期：2010.1.14

  The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.
• Dispiro 1,2,4 - trioxolane antimalarials
  申请人：MMV Medicines for Malaria Venture

  公开号：EP1514871B1

  公开（公告）日：2015-10-21
• US8754243B2
  申请人：——

  公开号：US8754243B2

  公开（公告）日：2014-06-17