4'-[3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-hydroxyaminopropylsufanyl]biphenyl-4-carbonitrile | 396131-73-0

• 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'-[3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-hydroxyaminopropylsufanyl]biphenyl-4-carbonitrile
• 英文别名: 4-[4-[3-(4,4-Dimethyl-2,5-dioxoimidazolidin-1-yl)-2-(hydroxyamino)propyl]sulfanylphenyl]benzonitrile
• CAS: 396131-73-0
• 化学式: C₂₁H₂₂N₄O₃S
• 分子量: 410.497
• InChiKey: JFBMESOUTGXPJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4'-[3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-hydroxyaminopropylsufanyl]biphenyl-4-carbonitrile 在 Oxone 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.5h， 生成 N-(1-(((4'-cyano(1,1'-biphenyl)-4-yl)sulfonyl)methyl)-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)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
• 作为产物：
  描述：

  4-(4-巯基苯基)苯甲腈 在 吡啶 、 盐酸 、 吡啶硼烷 、 盐酸羟胺 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 4'-[3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-hydroxyaminopropylsufanyl]biphenyl-4-carbonitrile
  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