(1S,4S,9S,10R,13S,14R,16R,18R)-10-hydroxy-11-(hydroxymethyl)-3,15,15,18-tetramethyl-5,8-dioxapentacyclo[11.5.1.01,9.04,9.014,16]nonadeca-2,11-diene-7,19-dione | 1460250-64-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二恶烷
• 英文名称: (1S,4S,9S,10R,13S,14R,16R,18R)-10-hydroxy-11-(hydroxymethyl)-3,15,15,18-tetramethyl-5,8-dioxapentacyclo[11.5.1.01,9.04,9.014,16]nonadeca-2,11-diene-7,19-dione
• CAS: 1460250-64-9
• 化学式: C₂₂H₂₈O₆
• 分子量: 388.461
• InChiKey: JNLCHZDHJZYCHJ-RQICCSSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ingenol-5,20-acetonide 在 盐酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 34.0h， 生成 (1S,4S,9S,10R,13S,14R,16R,18R)-10-hydroxy-11-(hydroxymethyl)-3,15,15,18-tetramethyl-5,8-dioxapentacyclo[11.5.1.01,9.04,9.014,16]nonadeca-2,11-diene-7,19-dione
  参考文献：
  名称：

  Syntheses, biological evaluation and SAR of ingenol mebutate analogues for treatment of actinic keratosis and non-melanoma skin cancer

  摘要：

  Ingenol mebutate is the active ingredient in Picato (R) a new drug for the treatment of actinic keratosis. A number of derivatives related to ingenol mebutate were prepared by chemical synthesis from ingenol with the purpose of investigating the SAR and potency in assays relating to pro-inflammatory effects (induction of PMN oxidative burst and keratinocyte cytokine release), the potential of cell death induction, as well as the chemical stability. By modifications of the ingenol scaffold several prerequisites for activity were identified. The chemical stability of the compounds could be linked to an acyl migration mechanism. We were able to find analogues of ingenol mebutate with comparable in vitro properties. Some key features for potent and more stable ingenol derivatives have been identified. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.038

文献信息

• Syntheses, biological evaluation and SAR of ingenol mebutate analogues for treatment of actinic keratosis and non-melanoma skin cancer
  作者：Xifu Liang、Gunnar Grue-Sørensen、Kristoffer Månsson、Per Vedsø、Anke Soor、Martin Stahlhut、Malene Bertelsen、Karen Margrethe Engell、Thomas Högberg

  DOI：10.1016/j.bmcl.2013.08.038

  日期：2013.10

  Ingenol mebutate is the active ingredient in Picato (R) a new drug for the treatment of actinic keratosis. A number of derivatives related to ingenol mebutate were prepared by chemical synthesis from ingenol with the purpose of investigating the SAR and potency in assays relating to pro-inflammatory effects (induction of PMN oxidative burst and keratinocyte cytokine release), the potential of cell death induction, as well as the chemical stability. By modifications of the ingenol scaffold several prerequisites for activity were identified. The chemical stability of the compounds could be linked to an acyl migration mechanism. We were able to find analogues of ingenol mebutate with comparable in vitro properties. Some key features for potent and more stable ingenol derivatives have been identified. (C) 2013 Elsevier Ltd. All rights reserved.