4-Phenyl-2-(phenylmethoxycarbamoyl)butanoic acid | 202652-70-8

• 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: 4-Phenyl-2-(phenylmethoxycarbamoyl)butanoic acid
• CAS: 202652-70-8
• 化学式: C₁₈H₁₉NO₄
• 分子量: 313.353
• InChiKey: HRCJRHBZGPAFKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Phenyl-2-(phenylmethoxycarbamoyl)butanoic acid 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 13.0h， 生成 N-Hydroxy-2-phenethyl-N'-[(S)-3-phenyl-1-(2-p-tolyl-ethylcarbamoyl)-propyl]-malonamide
  参考文献：
  名称：

  Design and Synthesis of Malonic Acid-Based Inhibitors of Human Neutrophil Collagenase (MMP8)

  摘要：

  For most of the known synthetic inhibitors of matrix metalloproteinases (MMPs), a substrate-like binding mode was postulated on the basis of X-ray crystallographic structures of MMP/inhibitor complexes. Conversely, the malonic acid-based inhibitor (2R,S)-HONH-CO-CH(i-Bu)-CO-Ala-Gly-NH2 was found to bind in a surprisingly different manner. Using this compound as a new lead structure, the interaction sites with human neutrophil collagenase (MMP8) were optimized with a series of iteratively designed analogues and with the help of X-ray structural analysis of selected inhibitors to finally produce low molecular weight nonpeptidic compounds of 500-1000-fold improved inhibitory potency.

  DOI：

  10.1021/jm9706426
• 作为产物：
  描述：

  2-Benzyloxycarbamoyl-4-phenyl-butyric acid ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以96%的产率得到4-Phenyl-2-(phenylmethoxycarbamoyl)butanoic acid
  参考文献：
  名称：

  Design and Synthesis of Malonic Acid-Based Inhibitors of Human Neutrophil Collagenase (MMP8)

  摘要：

  For most of the known synthetic inhibitors of matrix metalloproteinases (MMPs), a substrate-like binding mode was postulated on the basis of X-ray crystallographic structures of MMP/inhibitor complexes. Conversely, the malonic acid-based inhibitor (2R,S)-HONH-CO-CH(i-Bu)-CO-Ala-Gly-NH2 was found to bind in a surprisingly different manner. Using this compound as a new lead structure, the interaction sites with human neutrophil collagenase (MMP8) were optimized with a series of iteratively designed analogues and with the help of X-ray structural analysis of selected inhibitors to finally produce low molecular weight nonpeptidic compounds of 500-1000-fold improved inhibitory potency.

  DOI：

  10.1021/jm9706426

文献信息

• Design and Synthesis of Malonic Acid-Based Inhibitors of Human Neutrophil Collagenase (MMP8)
  作者：Erich Graf von Roedern、Frank Grams、Hans Brandstetter、Luis Moroder

  DOI：10.1021/jm9706426

  日期：1998.1.1

  For most of the known synthetic inhibitors of matrix metalloproteinases (MMPs), a substrate-like binding mode was postulated on the basis of X-ray crystallographic structures of MMP/inhibitor complexes. Conversely, the malonic acid-based inhibitor (2R,S)-HONH-CO-CH(i-Bu)-CO-Ala-Gly-NH2 was found to bind in a surprisingly different manner. Using this compound as a new lead structure, the interaction sites with human neutrophil collagenase (MMP8) were optimized with a series of iteratively designed analogues and with the help of X-ray structural analysis of selected inhibitors to finally produce low molecular weight nonpeptidic compounds of 500-1000-fold improved inhibitory potency.