6-bromo-4-[3-(2-methoxycarbonylethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]indole-1-carboxylic acid tert-butyl ester | 1440807-27-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-bromo-4-[3-(2-methoxycarbonylethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]indole-1-carboxylic acid tert-butyl ester
• CAS: 1440807-27-1
• 化学式: C₂₅H₂₆BrN₃O₅
• 分子量: 528.403
• InChiKey: PHOLUVYWMMOZFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.91
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  84.46
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  6-bromo-4-[3-(2-methoxycarbonylethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]indole-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以49%的产率得到3-[3-(6-bromo-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
• 作为产物：
  描述：

  6-bromo-1H-indole-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester 在 二氧化碳 、 偶氮二甲酸二异丙酯 、 二异丁基氢化铝 、 三苯基膦 作用下， 以 四氢呋喃 、 正庚烷 、 异丙醇 为溶剂， 反应 3.0h， 生成 6-bromo-4-[3-(2-methoxycarbonylethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]indole-1-carboxylic acid tert-butyl 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