(E)-4-[3-(dec-9-yn-1-yloxy)-3-oxoprop-1-en-1-yl]-1,2-phenylene diacetate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-4-[3-(dec-9-yn-1-yloxy)-3-oxoprop-1-en-1-yl]-1,2-phenylene diacetate
• 英文别名: dec-9-ynyl (E)-3-(3,4-diacetyloxyphenyl)prop-2-enoate
• 化学式: C₂₃H₂₈O₆
• 分子量: 400.472
• InChiKey: OUSGGHVJIJZOQD-FYWRMAATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-叠氮基丙醇 、 (E)-4-[3-(dec-9-yn-1-yloxy)-3-oxoprop-1-en-1-yl]-1,2-phenylene diacetate 在 copper(l) iodide 作用下， 以 水 、 叔丁醇 为溶剂， 反应 1.0h， 以62%的产率得到(E)-4-[3-((8-(1-(3-hydroxypropyl)-1H-1,2,3-triazol-4-yl)octyl)oxy)-3-oxoprop-1-en-1-yl]-1,2-phenylene diacetate
  参考文献：
  名称：

  Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors

  摘要：

  In this work the synthesis, structure activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 mu M in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.07.011
• 作为产物：
  描述：

  TRANS-咖啡酸 在 吡啶 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 苯 为溶剂， 反应 16.0h， 生成 (E)-4-[3-(dec-9-yn-1-yloxy)-3-oxoprop-1-en-1-yl]-1,2-phenylene diacetate
  参考文献：
  名称：

  Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors

  摘要：

  In this work the synthesis, structure activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 mu M in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.07.011

文献信息

• Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors
  作者：Daniela De Lucia、Oscar Méndez Lucio、Biagia Musio、Andreas Bender、Monika Listing、Sophie Dennhardt、Andreas Koeberle、Ulrike Garscha、Roberta Rizzo、Stefano Manfredini、Oliver Werz、Steven V. Ley

  DOI：10.1016/j.ejmech.2015.07.011

  日期：2015.8

  In this work the synthesis, structure activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 mu M in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization. (C) 2015 Published by Elsevier Masson SAS.