ingenol-3-(2-hydroxy-6-methyl-benzoate) | 1383427-01-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ingenol-3-(2-hydroxy-6-methyl-benzoate)
• 英文别名: [(1S,4S,5S,6R,9S,10R,12R,14R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 2-hydroxy-6-methylbenzoate
• CAS: 1383427-01-7
• 化学式: C₂₈H₃₄O₇
• 分子量: 482.574
• InChiKey: WPEGXFPGSRFUMB-BPQFZFCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	ingenol-5,20-acetonide	77573-43-4	C23H32O5	388.504
  ——	ingenol	30220-46-3	C20H28O5	348.439

反应信息

• 作为产物：
  描述：

  ingenol-5,20-acetonide 在 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 二乙胺 、 乙腈 为溶剂， 反应 2.0h， 生成 ingenol-3-(2-hydroxy-6-methyl-benzoate)
  参考文献：
  名称：

  Synthesis, biological evaluation and SAR of 3-benzoates of ingenol for treatment of actinic keratosis and non-melanoma skin cancer

  摘要：

  Ingenol 3-benzoates were investigated with respect to chemical stability, pro-inflammatory effects, cell death induction and PKC delta activation. A correlation between structure, chemical stability and biological activity was found and compared to ingenol mebutate (ingenol 3-angelate) used for field treatment of actinic keratosis. We also provided further support for involvement of PKC delta for induction of oxidative burst and cytokine release. Molecular modeling and dynamics calculations corroborated the essential interactions between key compounds and C1 domain of PKC delta. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.073

文献信息

• [EN] 3-ACYL-INGENOLS II<br/>[FR] 3-ACYL-INGÉNOLS II
  申请人：LEO PHARMA AS

  公开号：WO2012083954A1

  公开（公告）日：2012-06-28

  The invention relates to compounds of general formula I, (I), wherein R is wherein R is aryl substituted by R3; or R is (C3-Ci3)-cycloalkyl, (C3-Ci3)- cycloalkenyl or (C7-Ci3)-cycloalkynyl optionally substituted by R4; and pharmaceutically acceptable salts, hydrates, or solvates thereof, for use -alone or in combination with one or more other pharmaceutically active compounds- in therapy, for preventing, treating or ameliorating diseases or conditions responsive to stimulation of neutrophil oxidative burst, responsive to stimulation of keratinocyte IL-8 release or responsive to induction of necrosis.

  该发明涉及一般式I的化合物，其中R是芳基，被R3取代；或者R是(C3-C13)-环烷基，(C3-C13)-环烯基或(C7-C13)-环炔基，可选择性地被R4取代；以及其在治疗中的药用盐、水合物或溶剂化合物，可单独使用或与一个或多个其他药用活性化合物结合使用，用于预防、治疗或改善对中性粒细胞氧化爆发刺激敏感的疾病或症状，对角质细胞IL-8释放刺激敏感的疾病或症状，或对坏死诱导敏感的疾病或症状。
• US9656945B2
  申请人：——

  公开号：US9656945B2

  公开（公告）日：2017-05-23
• Synthesis, biological evaluation and SAR of 3-benzoates of ingenol for treatment of actinic keratosis and non-melanoma skin cancer
  作者：Gunnar Grue-Sørensen、Xifu Liang、Kristoffer Månsson、Per Vedsø、Morten Dahl Sørensen、Anke Soor、Martin Stahlhut、Malene Bertelsen、Karen Margrethe Engell、Thomas Högberg

  DOI：10.1016/j.bmcl.2013.11.073

  日期：2014.1

  Ingenol 3-benzoates were investigated with respect to chemical stability, pro-inflammatory effects, cell death induction and PKC delta activation. A correlation between structure, chemical stability and biological activity was found and compared to ingenol mebutate (ingenol 3-angelate) used for field treatment of actinic keratosis. We also provided further support for involvement of PKC delta for induction of oxidative burst and cytokine release. Molecular modeling and dynamics calculations corroborated the essential interactions between key compounds and C1 domain of PKC delta. (C) 2013 Elsevier Ltd. All rights reserved.