N-[2-(tert-butyldimethylsilanyloxy)-1-(4-(4-trifluoromethoxyphenoxy)phenylsulfonylmethyl)ethyl]-N-hydroxyformamide | 396131-88-7

• 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: N-[2-(tert-butyldimethylsilanyloxy)-1-(4-(4-trifluoromethoxyphenoxy)phenylsulfonylmethyl)ethyl]-N-hydroxyformamide
• 英文别名: N-[1-[tert-butyl(dimethyl)silyl]oxy-3-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpropan-2-yl]-N-hydroxyformamide
• CAS: 396131-88-7
• 化学式: C₂₃H₃₀F₃NO₇SSi
• 分子量: 549.64
• InChiKey: XQTXHQNYPIHLPE-UHFFFAOYSA-N

物化性质

• 沸点：
  591.2±60.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.39
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-[2-(tert-butyldimethylsilanyloxy)-1-(4-(4-trifluoromethoxyphenoxy)phenylsulfonylmethyl)ethyl]-N-hydroxyformamide 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以35%的产率得到(+/-)-N-hydroxy-N-[1-(hydroxymethyl)-2-[[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl]ethyl]formamide
  参考文献：
  名称：

  Phenoxyphenyl Sulfone N-Formylhydroxylamines (Retrohydroxamates) as Potent, Selective, Orally Bioavailable Matrix Metalloproteinase Inhibitors

  摘要：

  A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1' substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.

  DOI：

  10.1021/jm0103920
• 作为产物：
  描述：

  对氟苯甲砜 在 正丁基锂 、 羟胺 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 吡啶 、 正己烷 、 二氯甲烷 为溶剂， 反应 49.75h， 生成 N-[2-(tert-butyldimethylsilanyloxy)-1-(4-(4-trifluoromethoxyphenoxy)phenylsulfonylmethyl)ethyl]-N-hydroxyformamide
  参考文献：
  名称：

  Phenoxyphenyl Sulfone N-Formylhydroxylamines (Retrohydroxamates) as Potent, Selective, Orally Bioavailable Matrix Metalloproteinase Inhibitors

  摘要：

  A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1' substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.

  DOI：

  10.1021/jm0103920