2-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic acid ethyl ester | 1440808-24-1

• 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: 2-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic acid ethyl ester
• CAS: 1440808-24-1
• 化学式: C₂₄H₂₆BrN₃O₄
• 分子量: 500.392
• InChiKey: DLTQDMRPZSVWRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  2-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic acid ethyl ester 在 lithium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 以26%的产率得到2-[[3-[(6-Bromo-2-oxo-1,3-dihydroindol-4-yl)methyl]-2-oxobenzimidazol-1-yl]methyl]pentanoic 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-4-[3-(2-ethoxycarbonylpentyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]indole-1-carboxylic acid tert-butyl ester 在 pyridinium hydrobromide perbromide 、 溶剂黄146 、 三氟乙酸 、 锌 、 叔丁醇 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 2-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic acid ethyl 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