ingenol-3-tigliate | 1356187-27-3

• 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-tigliate
• 英文别名: ingenol-3-tiglate；ingenol-3-tiqlate；[(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] (E)-2-methylbut-2-enoate
• CAS: 1356187-27-3
• 化学式: C₂₅H₃₄O₆
• 分子量: 430.541
• InChiKey: VDJHFHXMUKFKET-WVXVGKHRSA-N

物化性质

• 沸点：
  576.9±50.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ingenol-5,20-acetonide-3-tiglate 在 盐酸 作用下， 以 水 为溶剂， 生成 ingenol-3-tigliate
  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

• METHOD OF ISOLATING INGENOL
  申请人：INDENA S.P.A.

  公开号：US20140243551A1

  公开（公告）日：2014-08-28

  The present invention relates to a new method for isolating ingenol (C 20 H 28 O 5 ) from mixtures of diterpenoid esters and ingenol esters in a single step. Ingenol isolated by means of this method can be used as a precursor for the synthesis of biologically active ingenol derivatives, such as ingenol-3-angelate and ingenol-3-tigliate.

  本发明涉及一种新的方法，用于在单步中从二萜酯和英吉诺酯的混合物中分离出英吉诺醇（C20H28O5）。通过这种方法分离出的英吉诺醇可以用作合成生物活性英吉诺醇衍生物（如英吉诺-3-安吉酸酯和英吉诺-3-提格酸酯）的前体。
• [EN] A METHOD OF PRODUCING INGENOL-3-ANGELATE<br/>[FR] PROCÉDÉ DE PRODUCTION D'INGÉNOL-3-ANGÉLATE
  申请人：LEO PHARMA AS

  公开号：WO2012010172A1

  公开（公告）日：2012-01-26

  The present invention relates to methods of producing ingenol-3-angelate (I) from ingenol (II). Formula (I) and (II). Furthermore, the invention relates to intermediates useful for the synthesis of ingenol-3-angelate (I) from ingenol (II) and to methods of producing said intermediates.

  本发明涉及从英吉利醇(II)制备英吉利醇-3-安吉酯(I)的方法。公式(I)和(II)。此外，本发明涉及用于从英吉利醇(II)合成英吉利醇-3-安吉酯(I)的中间体以及制备该中间体的方法。
• [EN] INGENOL-3-ACYLATES I<br/>[FR] INGÉNOL-3-ACYLATES I
  申请人：LEO PHARMA AS

  公开号：WO2012085189A1

  公开（公告）日：2012-06-28

  The invention relates to compounds of general formula (I) wherein R is (C1-C7)alkyl, (C2-C7)alkenyl or (C2-C7)alkynyl; wherein R is substituted with R1; 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.

  本发明涉及一般式(I)的化合物，其中R为(C1-C7)烷基，(C2-C7)烯基或(C2-C7)炔基；其中R被R1取代；以及其药学上可接受的盐、水合物或溶剂化物，用于治疗、预防、治疗或改善对中性粒细胞氧化爆发刺激、角质细胞IL-8释放刺激或坏死诱导反应敏感的疾病或病情，可以单独使用或与一个或多个其他药物活性化合物结合使用。
• METHOD OF PRODUCING INGENOL-3-ANGELATE
  申请人：Högberg Thomas

  公开号：US20130177952A1

  公开（公告）日：2013-07-11

  The present invention relates to methods of producing ingenol-3-angelate (I) from ingenol (II). Furthermore, the invention relates to intermediates useful for the synthesis of ingenol-3-angelate (I) from ingenol (II) and to methods of producing said intermediates.

  本发明涉及从英吉利醇（II）制备英吉利醇-3-丁二酸酯（I）的方法。此外，本发明还涉及用于从英吉利醇（II）合成英吉利醇-3-丁二酸酯（I）的中间体以及制备所述中间体的方法。
• Semisynthesis of Ingenol 3-Angelate (PEP005): Efficient Stereoconservative Angeloylation of Alcohols
  作者：Xifu Liang、Gunnar Grue-Sørensen、Anders Petersen、Thomas Högberg

  DOI：10.1055/s-0032-1317415

  日期：——

  A high-yielding method was developed for the preparation of ingenol 3-angelate (PEP005, ingenol mebutate) via the corresponding 5,20-acetonide without concomitant isomerization of the angelate (Z-form) to the corresponding tiglate (E-form). The general scope of the stereoconservative esterification method was further evaluated on several different alcohols, giving the angelates in up to quantitative yield without isomerization to the tiglate.