4-[(4-benzyloxy-2,3,5,6-tetrafluorobenzyl)[1,2,4]triazol-4-ylamino]benzonitrile | 946007-72-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(4-benzyloxy-2,3,5,6-tetrafluorobenzyl)[1,2,4]triazol-4-ylamino]benzonitrile
• 英文别名: 4-[(2,3,5,6-Tetrafluoro-4-phenylmethoxyphenyl)methyl-(1,2,4-triazol-4-yl)amino]benzonitrile
• CAS: 946007-72-3
• 化学式: C₂₃H₁₅F₄N₅O
• 分子量: 453.399
• InChiKey: DQNIZRAAKNSQAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-[(4-benzyloxy-2,3,5,6-tetrafluorobenzyl)[1,2,4]triazol-4-ylamino]benzonitrile 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 18.0h， 以83%的产率得到4-{[(2,3,5,6-tetrafluoro-4-hydroxyphenyl)methyl](4H-1,2,4-triazol-4-yl)amino}benzonitrile
  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：

  对氟苯腈 在 potassium tert-butylate 、 sodium hydride 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[(4-benzyloxy-2,3,5,6-tetrafluorobenzyl)[1,2,4]triazol-4-ylamino]benzonitrile
  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