3-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-yl]propionic acid methyl ester | 1440807-63-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 3-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-yl]propionic acid methyl ester
• CAS: 1440807-63-5
• 化学式: C₂₀H₁₈BrN₃O₄
• 分子量: 444.285
• InChiKey: NMMCJZPYCMYYHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.67
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  82.33
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-yl]propionic acid methyl ester 在 lithium hydroxide monohydrate 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 以32%的产率得到3-{3-[(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-yl)methyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}propanoic acid
  参考文献：
  名称：

  Discovery of Potent, Selective Chymase Inhibitors via Fragment Linking Strategies

  摘要：

  Chymase plays an important and diverse role in the homeostasis of a number of cardiovascular processes. Herein, we describe the identification of potent, selective chymase inhibitors, developed using fragment-based, structure-guided linking and optimization techniques. High-concentration biophysical screening methods followed by high-throughput crystallography identified an oxindole fragment bound to the S1 pocket of the protein exhibiting a novel interaction pattern hitherto not observed in chymase inhibitors. X-ray crystallographic structures were used to guide the elaboration/linking of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over cathepsin G and that mitigated a number of liabilities associated with poor physicochemical properties of the series it was derived from.

  DOI：

  10.1021/jm400138z
• 作为产物：
  描述：

  6-bromo-1H-indole-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester 在 pyridinium hydrobromide perbromide 、 二氧化碳 、 偶氮二甲酸二异丙酯 、 二异丁基氢化铝 、 溶剂黄146 、 三苯基膦 、 三氟乙酸 、 锌 、 叔丁醇 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 、 异丙醇 为溶剂， 反应 10.0h， 生成 3-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-yl]propionic acid methyl ester
  参考文献：
  名称：

  Discovery of Potent, Selective Chymase Inhibitors via Fragment Linking Strategies

  摘要：

  Chymase plays an important and diverse role in the homeostasis of a number of cardiovascular processes. Herein, we describe the identification of potent, selective chymase inhibitors, developed using fragment-based, structure-guided linking and optimization techniques. High-concentration biophysical screening methods followed by high-throughput crystallography identified an oxindole fragment bound to the S1 pocket of the protein exhibiting a novel interaction pattern hitherto not observed in chymase inhibitors. X-ray crystallographic structures were used to guide the elaboration/linking of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over cathepsin G and that mitigated a number of liabilities associated with poor physicochemical properties of the series it was derived from.

  DOI：

  10.1021/jm400138z