4-benzyloxytetrafluorobenzyl alcohol | 161497-42-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-benzyloxytetrafluorobenzyl alcohol
• 英文别名: (4-benzyloxy-2,3,5,6-tetrafluorophenyl)methanol；(2,3,5,6-Tetrafluoro-4-phenylmethoxyphenyl)methanol
• CAS: 161497-42-3
• 化学式: C₁₄H₁₀F₄O₂
• 分子量: 286.226
• InChiKey: VQFZBUZGWGPJDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-benzyloxytetrafluorobenzyl alcohol 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 以93%的产率得到1-benzyloxy-4-chloromethyl-2,3,5,6-tetrafluorobenzene
  参考文献：
  名称：

  Dual Aromatase−Steroid Sulfatase Inhibitors

  摘要：

  By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.

  DOI：

  10.1021/jm061462b
• 作为产物：
  描述：

  methyl 2,3,5,6-tetrafluoro-4-hydroxybenzoate 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-benzyloxytetrafluorobenzyl alcohol
  参考文献：
  名称：

  Dual Aromatase−Steroid Sulfatase Inhibitors

  摘要：

  By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.

  DOI：

  10.1021/jm061462b

文献信息

• Mechanism and Mechanism-Based Inactivation of 4-Hydroxyphenylpyruvate Dioxygenase
  作者：B.J.R. Forbes、G.A. Gordon

  DOI：10.1006/bioo.1994.1028

  日期：1994.12

  Six substrate analogs of 4-hydroxyphenylpyruvate, specifically pentafluorophenylpyruvate, 4-hydroxytetrafluorophenylpyruvate,2-thienylpyruvate, 3-thienylpyruvate, thiophenol oxalate, and p-thiocresoloxalate were synthesized and their interactions with porcine liver 4-hydroxyphenylpyruvate dioxygenase investigated. Both pentafluorophenylpyruvate and thiophenol oxalate are competitive inhibitors of the enzyme with Ki values of 14 and 150 mu M, respectively, but p-thiocresol oxalate has no effect on the enzymic activity. The other three substrate analogs are both substrates and mechanism-based inactivators of the enzyme with the following kinetic characteristics (compound, K-m, V-max, k(mact), K', partition ratio) at pH 6.0, 37 degrees C, and an air atmosphere: 4-hydroxytetrafluorophenylpyruvate, 50 mu M, 1.9 mkat/ kg, 1.5/min, 70 mu M 4.2; 2-thienylpyruvate, 500 mu M, 7.8 mkat/kg, 0.6/min, 400 CLM, 41; 3thienylpymvate, 250 mu M, 2 9 mkatikg, 0.6/min, 300 CLM, 22. When inactivated, the dioxygenase was found to contain per mole of active enzyme, 0.78 mol of label from 3-thienyt3 [3H]pyruvate and 0.85 mol of label from 4-hydroxytetrafluorophenyl-3 [3H]pyruvate. The product formed from the enzyme-catalyzed oxidation of 3-thienylpyruvate was determined to be 3-carboxymethyl-3-thiolene-2-one. The implication of these results to the mechanism of the dioxygenase is considered, (C) 1994 Academic Press, Inc.