(+/-)-N-[1-[(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl]-2-[[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl]ethyl]-N-hydroxyformamide

• 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-[1-[(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl]-2-[[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl]ethyl]-N-hydroxyformamide
• 英文别名: N-[1-[(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl]-2-[[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl]ethyl]-N-hydroxyformamide；N-Hydroxy-N-{1-(3-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl)-2-[4-(4-trifluoromethoxy-phenoxy)-benzenesulfonyl]-ethyl}-formamide；N-hydroxy-N-[1-(3-methyl-2,6-dioxopyrimidin-1-yl)-3-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylpropan-2-yl]formamide
• 化学式: C₂₂H₂₀F₃N₃O₈S
• 分子量: 543.477
• InChiKey: IBBWGNRWVQJYIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  142
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1-甲基尿嘧啶 在 吡啶 、 盐酸 、 Oxone 、 吡啶硼烷 、 盐酸羟胺 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.5h， 生成 (+/-)-N-[1-[(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl]-2-[[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonyl]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

文献信息

• Reverse hydroxamate inhibitors of matrix metalloproteinases
  申请人：Abbott Laboratories

  公开号：US06294573B1

  公开（公告）日：2001-09-25

  Compounds having the formula are matrix metalloproteinase inhibitors. Also disclosed are matrix metalloproteinase-inhibiting compositions and methods of inhibiting matrix metalloproteinase in a mammal.

  具有以下化学式的化合物是基质金属蛋白酶抑制剂。还公开了抑制基质金属蛋白酶的组合物和方法，用于在哺乳动物中抑制基质金属蛋白酶。
• US6294573B1
  申请人：——

  公开号：US6294573B1

  公开（公告）日：2001-09-25