O-tert-butyl-3-(4-iodophenoxy)propanohydroxamic acid | 191228-69-0

• 英文名称: O-tert-butyl-3-(4-iodophenoxy)propanohydroxamic acid
• 英文别名: N-tert-butoxy-3-(4-iodophenoxy)propionamide；O-tert-butyl 3-(4-iodophenoxy)propanohydroxamic acid；3-(4-iodophenoxy)-N-[(2-methylpropan-2-yl)oxy]propanamide
• CAS: 191228-69-0
• 化学式: C₁₃H₁₈INO₃
• 分子量: 363.195
• InChiKey: WSVAXQNLPBZFKN-UHFFFAOYSA-N

物化性质

• 密度：
  1.471±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 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-3-(4-iodophenoxy)propanohydroxamic acid 在 四(三苯基膦)钯 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 45.84h， 生成 3-[4-[3-(cyanomethyl)phenyl]phenoxy]propanohydroxamic acid
  参考文献：
  名称：

  An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1

  摘要：

  Fragment based drug discovery remains a successful tool for pharmaceutical lead discovery. Although based upon the principle of thermodynamic additivity, the underlying thermodynamic basis is poorly understood. A thermodynamic additivity analysis was performed using stromelysin-1 and a series of biphenyl hydroxamate ligands identified through fragment additivity. Our studies suggest that, in this instance, additivity arises from enthalpic effects, while interaction entropies are unfavorable; this thermodynamic behavior is masked by proton transfer. Evaluation of the changes in constant pressure heat capacities during binding suggest that solvent exclusion from the binding site does not account for the dramatic affinity enhancements observed. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.032
• 作为产物：
  描述：

  4-碘苯酚 在 氯化亚砜 、 potassium tert-butylate 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 29.0h， 生成 O-tert-butyl-3-(4-iodophenoxy)propanohydroxamic acid
  参考文献：
  名称：

  An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1

  摘要：

  Fragment based drug discovery remains a successful tool for pharmaceutical lead discovery. Although based upon the principle of thermodynamic additivity, the underlying thermodynamic basis is poorly understood. A thermodynamic additivity analysis was performed using stromelysin-1 and a series of biphenyl hydroxamate ligands identified through fragment additivity. Our studies suggest that, in this instance, additivity arises from enthalpic effects, while interaction entropies are unfavorable; this thermodynamic behavior is masked by proton transfer. Evaluation of the changes in constant pressure heat capacities during binding suggest that solvent exclusion from the binding site does not account for the dramatic affinity enhancements observed. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.032

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。
• Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR
  作者：P. J. Hajduk、G. Sheppard、D. G. Nettesheim、E. T. Olejniczak、S. B. Shuker、R. P. Meadows、D. H. Steinman、G. M. Carrera、P. A. Marcotte、J. Severin、K. Walter、H. Smith、E. Gubbins、R. Simmer、T. F. Holzman、D. W. Morgan、S. K. Davidsen、J. B. Summers、S. W. Fesik

  DOI：10.1021/ja9702778

  日期：1997.6.1

  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.
• BIPHENYL HYDROXAMATE INHIBITORS OF MATRIX METALLOPROTEINASES
  申请人：Abbott Laboratories

  公开号：EP0874808A1

  公开（公告）日：1998-11-04
• US5665777A
  申请人：——

  公开号：US5665777A

  公开（公告）日：1997-09-09
• [EN] BIPHENYL HYDROXAMATE INHIBITORS OF MATRIX METALLOPROTEINASES<br/>[FR] INHIBITEURS DE METALLOPROTEINASES MATRICIELLES, A L'HYDROXAMATE BIPHENYLIQUE
  申请人：ABBOTT LABORATORIES

  公开号：WO1997018188A1

  公开（公告）日：1997-05-22

  (EN) Compounds of formula (I), or a pharmaceutically acceptable salt thereof inhibit matrix metalloproteinases and TNF$g(a) secretion and are useful in the treatment of inflammatory disease states. Also disclosed are matrix metalloproteinases and TNF$g(a) secretion inhibiting compositions and a method for inhibiting matrix metalloproteinases and TNF$g(a) secretion.(FR) L'invention concerne des composés de formule (I) ou un sel pharmaceutiquement acceptable de ceux-ci, qui inhibent la sécrétion des métalloprotéinases matricielles et de TNF$g(a) et sont utiles dans le traitement de pathologies inflammatoires. Elle porte aussi sur des compositions inhibant la sécrétion de métalloprotéinases matricielles et de TNF$g(a) et sur une méthode d'inhibition de la sécrétion de métalloprotéinases matricielles et de TNF$g(a).