5,5'-difluorocurcumin | 1616504-30-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 5,5'-difluorocurcumin
• 英文别名: (1E,6E)-1,7-bis(3-fluoro-4-hydroxy-5-methoxyphenyl)hepta-1,6-diene-3,5-dione
• CAS: 1616504-30-3
• 化学式: C₂₁H₁₈F₂O₆
• 分子量: 404.367
• InChiKey: WYTDPUYUSRWWCD-GGWOSOGESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氟-4-羟基-5-甲氧基苯甲醛 、 乙酰丙酮 在 boron trioxide 、 硼酸三甲酯 、 正丁胺 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以50%的产率得到5,5'-difluorocurcumin
  参考文献：
  名称：

  SAR Studies on Curcumin’s Pro-inflammatory Targets: Discovery of Prenylated Pyrazolocurcuminoids as Potent and Selective Novel Inhibitors of 5-Lipoxygenase

  摘要：

  The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investigated, identifying prostaglandin E-2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high affinity targets. A comparative structure-activity study revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii) hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis along with reduced 5-LO product levels. Other pro-inflammatory targets of curcumin (ie., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-kappa B, nuclear factor-erythroid 2-related factor-2, and signal transducer and activator of transcription 3) were hardly affected by 11. The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific interactions rather than redox or membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin.

  DOI：

  10.1021/jm500308c

文献信息

• SAR Studies on Curcumin’s Pro-inflammatory Targets: Discovery of Prenylated Pyrazolocurcuminoids as Potent and Selective Novel Inhibitors of 5-Lipoxygenase
  作者：Andreas Koeberle、Eduardo Muñoz、Giovanni B. Appendino、Alberto Minassi、Simona Pace、Antonietta Rossi、Christina Weinigel、Dagmar Barz、Lidia Sautebin、Diego Caprioglio、Juan A. Collado、Oliver Werz

  DOI：10.1021/jm500308c

  日期：2014.7.10

  The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investigated, identifying prostaglandin E-2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high affinity targets. A comparative structure-activity study revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii) hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis along with reduced 5-LO product levels. Other pro-inflammatory targets of curcumin (ie., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-kappa B, nuclear factor-erythroid 2-related factor-2, and signal transducer and activator of transcription 3) were hardly affected by 11. The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific interactions rather than redox or membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin.