9-(Phenylmethoxycarbamoyl)tricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaene-9-carboxylic acid | 211301-22-3

• 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: 9-(Phenylmethoxycarbamoyl)tricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaene-9-carboxylic acid
• CAS: 211301-22-3
• 化学式: C₂₄H₂₁NO₄
• 分子量: 387.435
• InChiKey: GQVWEWATGSJHJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  9-(Phenylmethoxycarbamoyl)tricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaene-9-carboxylic 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 5,7-Dihydro-dibenzo[a,c]cycloheptene-6,6-dicarboxylic acid hydroxyamide (3-phenyl-propyl)-amide
  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：

  5,7-dihydro-dibenzo[a,c]cycloheptene-6,6-dicarboxylic 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 50.0h， 生成 9-(Phenylmethoxycarbamoyl)tricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaene-9-carboxylic acid
  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