O-tert-butyl 5-(4-iodophenoxy)pentanohydroxamic acid | 191228-67-8

• 英文名称: O-tert-butyl 5-(4-iodophenoxy)pentanohydroxamic acid
• 英文别名: 5-(4-iodophenoxy)-N-[(2-methylpropan-2-yl)oxy]pentanamide
• CAS: 191228-67-8
• 化学式: C₁₅H₂₂INO₃
• 分子量: 391.249
• InChiKey: RWDJQMMYGUFMMZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  O-tert-butyl 5-(4-iodophenoxy)pentanohydroxamic acid 在 四(三苯基膦)钯 六甲基二锡 、 三氟乙酸 作用下， 以 甲苯 为溶剂， 反应 42.03h， 生成 5-[4-[3-(cyanomethyl)phenyl]phenoxy]pentanohydroxamic acid
  参考文献：
  名称：

  Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR

  摘要：

  With the use of an NMR-based method, potent (IC50 < 25 nM) nonpeptide inhibitors of the matrix metalloproteinase stromelysin (MMP-3) were discovered. The method, called SAR by NMR (for structure-activity relationships by nuclear magnetic resonance), involves the identification, optimization, and linking of compounds that bind to proximal sites on a protein. Using this technique, two ligands that bind weakly to stromelysin (acetohydroxamic acid, K-D = 17 mM; 3-(cyanomethyl)-4'-hydroxybiphenyl, K-D = 0.02 mM) were identified. On the basis of NMR-derived structural information, the two fragments were connected to produce a 15 nM inhibitor of this enzyme. This compound was rapidly discovered (less than 6 months) and required only a minimal amount of chemical synthesis. These studies indicate that the SAR by NMR method can be effectively applied to enzymes to yield potent lead inhibitors-an important part of the drug discovery process.

  DOI：

  10.1021/ja9702778
• 作为产物：
  描述：

  5-(4-iodophenoxy)pentanoic acid 在 sodium hydroxide 、 氯化亚砜 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.5h， 生成 O-tert-butyl 5-(4-iodophenoxy)pentanohydroxamic acid
  参考文献：
  名称：

  Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR

  摘要：

  With the use of an NMR-based method, potent (IC50 < 25 nM) nonpeptide inhibitors of the matrix metalloproteinase stromelysin (MMP-3) were discovered. The method, called SAR by NMR (for structure-activity relationships by nuclear magnetic resonance), involves the identification, optimization, and linking of compounds that bind to proximal sites on a protein. Using this technique, two ligands that bind weakly to stromelysin (acetohydroxamic acid, K-D = 17 mM; 3-(cyanomethyl)-4'-hydroxybiphenyl, K-D = 0.02 mM) were identified. On the basis of NMR-derived structural information, the two fragments were connected to produce a 15 nM inhibitor of this enzyme. This compound was rapidly discovered (less than 6 months) and required only a minimal amount of chemical synthesis. These studies indicate that the SAR by NMR method can be effectively applied to enzymes to yield potent lead inhibitors-an important part of the drug discovery process.

  DOI：

  10.1021/ja9702778

文献信息

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

  公开号：US05665777A1

  公开（公告）日：1997-09-09

  Compounds of formula ##STR1## or a pharmaceutically acceptable salt thereof inhibit matrix metalloproteinases and TNF.alpha. secretion and are useful in the treatment of inflammatory disease states. Also disclosed are matrix metalloproteinases and TNF.alpha. secretion inhibiting compositions and a method for inhibiting matrix metalloproteinases and TNF.alpha. secretion.

  式##STR1##的化合物或其药用可接受的盐抑制基质金属蛋白酶和TNF.alpha.分泌，并且在治疗炎症性疾病状态中是有用的。还公开了抑制基质金属蛋白酶和TNF.alpha.分泌的组合物和抑制基质金属蛋白酶和TNF.alpha.分泌的方法。
• BIPHENYL HYDROXAMATE INHIBITORS OF MATRIX METALLOPROTEINASES
  申请人：Abbott Laboratories

  公开号：EP0874808B1

  公开（公告）日：2003-04-09
• US5665777A
  申请人：——

  公开号：US5665777A

  公开（公告）日：1997-09-09