methyl (4-(4-trifluoromethoxyphenoxy)phenylsulfanyl)acetate | 361547-22-0

• 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: methyl (4-(4-trifluoromethoxyphenoxy)phenylsulfanyl)acetate
• 英文别名: Methyl 2-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfanylacetate
• CAS: 361547-22-0
• 化学式: C₁₆H₁₃F₃O₄S
• 分子量: 358.338
• InChiKey: LFUPXNYMMCLYNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  70.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (4-(4-trifluoromethoxyphenoxy)phenylsulfanyl)acetate 在 Oxone 、 sodium tetrahydroborate 、 正丁基锂 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 1-dimethylsulfamoylmethyl-2-(4-(4-trifluoromethoxyphenoxy)phenylsulfonyl)ethyl methanesulfonate
  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：

  对三氟甲氧基苯酚 在 10percent Pd/C 盐酸 、 氢氧化钾 、 氯化亚砜 、 potassium tert-butylate 、 氢气 、 sodium nitrite 作用下， 以 吡啶 、 甲醇 、 乙醇 为溶剂， 100.0 ℃ 、405.33 kPa 条件下， 反应 42.5h， 生成 methyl (4-(4-trifluoromethoxyphenoxy)phenylsulfanyl)acetate
  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。
• 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.