5-[4-(4-Cyanophenyl)phenoxy]pentanoyl chloride | 178959-36-9

• 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: 5-[4-(4-Cyanophenyl)phenoxy]pentanoyl chloride
• 英文别名: 5-[4-(4-cyanophenyl)phenoxy]pentanoyl chloride
• CAS: 178959-36-9
• 化学式: C₁₈H₁₆ClNO₂
• 分子量: 313.784
• InChiKey: FYYHDAVPNLKFOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-[4-(4-Cyanophenyl)phenoxy]pentanoyl chloride 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 5-(4'-cyanobiphenyl-4-yloxy)pentanoic acid hydroxyamide
  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-溴戊酸乙酯 在 氢氧化钾 、 氯化亚砜 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 5-[4-(4-Cyanophenyl)phenoxy]pentanoyl chloride
  参考文献：
  名称：

  Synthesis and Phase Behavior of Side-Group Liquid Crystalline Polymers in Nematic Solvents

  摘要：

  A model system of side-group liquid crystalline polymers (SGLCPs) with systematically varied molecular weight (from 78 to 420 kg/mol; PDI less than or equal to 1.16) and spacer length (8-12 atoms long) was prepared by polymer analogous synthesis. Matching the structure of the mesogenic units to that of the nematic solvent produced excellent solubility, even at molecular weights an order of magnitude greater than in prior literature on SGLCP solutions. Addition of up to 10 wt % polymer did not affect the ordinary and extraordinary refractive indices of the nematic host (4-pentyl-4'-cyanobiphenyl, 5CB), indicating that the order parameter was not significantly affected by the polymer.

  DOI：

  10.1021/ma0348268

文献信息

• 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.
• An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1
  作者：Erin M. Wilfong、Yu Du、Eric J. Toone

  DOI：10.1016/j.bmcl.2012.05.032

  日期：2012.10

  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.
• Synthesis and Phase Behavior of Side-Group Liquid Crystalline Polymers in Nematic Solvents
  作者：Michael D. Kempe、Julia A. Kornfield、Christopher K. Ober、Steven D. Smith

  DOI：10.1021/ma0348268

  日期：2004.5.1

  A model system of side-group liquid crystalline polymers (SGLCPs) with systematically varied molecular weight (from 78 to 420 kg/mol; PDI less than or equal to 1.16) and spacer length (8-12 atoms long) was prepared by polymer analogous synthesis. Matching the structure of the mesogenic units to that of the nematic solvent produced excellent solubility, even at molecular weights an order of magnitude greater than in prior literature on SGLCP solutions. Addition of up to 10 wt % polymer did not affect the ordinary and extraordinary refractive indices of the nematic host (4-pentyl-4'-cyanobiphenyl, 5CB), indicating that the order parameter was not significantly affected by the polymer.