methyl 4-[3-[formyl(hydroxy)amino]-4-({4-[4-(trifluoromethoxy)phenoxy]phenyl}sulfonyl)butyl]benzoate | 361546-32-9

• 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: methyl 4-[3-[formyl(hydroxy)amino]-4-({4-[4-(trifluoromethoxy)phenoxy]phenyl}sulfonyl)butyl]benzoate
• 英文别名: 4-{3-(Formyl-hydroxy-amino)-4-[4-(4-trifluoromethoxy-phenoxy)-benzenesulfonyl]-butyl}-benzoic acid methyl ester；methyl 4-[3-[formyl(hydroxy)amino]-4-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylbutyl]benzoate
• CAS: 361546-32-9
• 化学式: C₂₆H₂₄F₃NO₈S
• 分子量: 567.54
• InChiKey: CATBJIHGLQLCIT-UHFFFAOYSA-N

物化性质

• 熔点：
  153-154 °C
• 沸点：
  702.2±70.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl 4-[3-[formyl(hydroxy)amino]-4-({4-[4-(trifluoromethoxy)phenoxy]phenyl}sulfonyl)butyl]benzoate 在 氢氧化钾 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 16.0h， 以71%的产率得到4-[3-[formyl(hydroxy)amino]-4-({4-[4-(trifluoromethoxy)phenoxy]phenyl}sulfonyl)butyl]benzoic acid
  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 sodium tetrahydroborate 、 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 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 48.75h， 生成 methyl 4-[3-[formyl(hydroxy)amino]-4-({4-[4-(trifluoromethoxy)phenoxy]phenyl}sulfonyl)butyl]benzoate
  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

• US6294573B1
  申请人：——

  公开号：US6294573B1

  公开（公告）日：2001-09-25
• Phenoxyphenyl Sulfone <i>N</i>-Formylhydroxylamines (Retrohydroxamates) as Potent, Selective, Orally Bioavailable Matrix Metalloproteinase Inhibitors
  作者：Carol K. Wada、James H. Holms、Michael L. Curtin、Yujia Dai、Alan S. Florjancic、Robert B. Garland、Yan Guo、H. Robin Heyman、Jamie R. Stacey、Douglas H. Steinman、Daniel H. Albert、Jennifer J. Bouska、Ildiko N. Elmore、Carole L. Goodfellow、Patrick A. Marcotte、Paul Tapang、Douglas W. Morgan、Michael R. Michaelides、Steven K. Davidsen

  DOI：10.1021/jm0103920

  日期：2002.1.1

  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.