2-Benzyl-2-benzyloxy-malonic acid diethyl ester | 211301-14-3

• 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: 2-Benzyl-2-benzyloxy-malonic acid diethyl ester
• 英文别名: Diethyl 2-benzyl-2-phenylmethoxypropanedioate
• CAS: 211301-14-3
• 化学式: C₂₁H₂₄O₅
• 分子量: 356.419
• InChiKey: SSYAUHMGZIEKSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Benzyl-2-benzyloxy-malonic acid diethyl ester 在 N-甲基吗啉 、 氢氧化钾 、 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 、 乙醇 、 水 为溶剂， 反应 62.0h， 生成 2,N-Dibenzyl-2,N'-bis-benzyloxy-malonamide
  参考文献：
  名称：

  Bis-Substituted Malonic Acid Hydroxamate Derivatives as Inhibitors of Human Neutrophil Collagenase (MMP8)

  摘要：

  Malonic acid hydroxamate derivatives bis-substituted at the methylene group were synthesized as potential nonpeptidic inhibitors of human neutrophil collagenase (MMP8). The presence of an aromatic residue both at the C2 malonic acid position and in the C-terminal tail for hydrophobic interactions with the surface-exposed S1 binding site and the S1' pocket of the enzyme, respectively, was found to be sufficient for submicromolar inhibition potencies. For optimal insertion of the aryl amide group into the hydrophobic S1' pocket, spacing of the C-terminal phenyl group by at least a SC-chain was required. In view of these results the achiral indan-2,2-dicarboxylic acid was used to mimic the 2-benzyl-2-methylmalonic acid residue, and its derivatization to the 3-phenylpropyl amide hydroxamate produced a potent, achiral, low-mass inhibitor of MMP8 (K-i = 0.3 mu M), the binding mode of which was unambiguously determined by X-ray crystallographic analysis.

  DOI：

  10.1021/jm980112p
• 作为产物：
  描述：

  2-(苄氧基)丙二酸二乙酯 、 溴甲苯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以59%的产率得到2-Benzyl-2-benzyloxy-malonic acid diethyl ester
  参考文献：
  名称：

  Bis-Substituted Malonic Acid Hydroxamate Derivatives as Inhibitors of Human Neutrophil Collagenase (MMP8)

  摘要：

  Malonic acid hydroxamate derivatives bis-substituted at the methylene group were synthesized as potential nonpeptidic inhibitors of human neutrophil collagenase (MMP8). The presence of an aromatic residue both at the C2 malonic acid position and in the C-terminal tail for hydrophobic interactions with the surface-exposed S1 binding site and the S1' pocket of the enzyme, respectively, was found to be sufficient for submicromolar inhibition potencies. For optimal insertion of the aryl amide group into the hydrophobic S1' pocket, spacing of the C-terminal phenyl group by at least a SC-chain was required. In view of these results the achiral indan-2,2-dicarboxylic acid was used to mimic the 2-benzyl-2-methylmalonic acid residue, and its derivatization to the 3-phenylpropyl amide hydroxamate produced a potent, achiral, low-mass inhibitor of MMP8 (K-i = 0.3 mu M), the binding mode of which was unambiguously determined by X-ray crystallographic analysis.

  DOI：

  10.1021/jm980112p

文献信息

• Bis-Substituted Malonic Acid Hydroxamate Derivatives as Inhibitors of Human Neutrophil Collagenase (MMP8)
  作者：Erich Graf von Roedern、Hans Brandstetter、Richard A. Engh、Wolfram Bode、Frank Grams、Luis Moroder

  DOI：10.1021/jm980112p

  日期：1998.7.1

  Malonic acid hydroxamate derivatives bis-substituted at the methylene group were synthesized as potential nonpeptidic inhibitors of human neutrophil collagenase (MMP8). The presence of an aromatic residue both at the C2 malonic acid position and in the C-terminal tail for hydrophobic interactions with the surface-exposed S1 binding site and the S1' pocket of the enzyme, respectively, was found to be sufficient for submicromolar inhibition potencies. For optimal insertion of the aryl amide group into the hydrophobic S1' pocket, spacing of the C-terminal phenyl group by at least a SC-chain was required. In view of these results the achiral indan-2,2-dicarboxylic acid was used to mimic the 2-benzyl-2-methylmalonic acid residue, and its derivatization to the 3-phenylpropyl amide hydroxamate produced a potent, achiral, low-mass inhibitor of MMP8 (K-i = 0.3 mu M), the binding mode of which was unambiguously determined by X-ray crystallographic analysis.