3-[2-Oxo-3-[(2-oxo-1,3-dihydroindol-4-yl)methyl]benzimidazol-1-yl]hexanoic acid | 1440806-76-7

• 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-[2-Oxo-3-[(2-oxo-1,3-dihydroindol-4-yl)methyl]benzimidazol-1-yl]hexanoic acid
• 英文别名: 3-[2-oxo-3-[(2-oxo-1,3-dihydroindol-4-yl)methyl]benzimidazol-1-yl]hexanoic acid
• CAS: 1440806-76-7
• 化学式: C₂₂H₂₃N₃O₄
• 分子量: 393.442
• InChiKey: IISHZWLYDWPZIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  90
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  吲哚-4-羧酸甲酯 在 4-二甲氨基吡啶 、 pyridinium hydrobromide perbromide 、 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 、 lithium hydroxide 、 锌 、 叔丁醇 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正庚烷 、 二氯甲烷 、 水 为溶剂， 反应 12.25h， 生成 3-[2-Oxo-3-[(2-oxo-1,3-dihydroindol-4-yl)methyl]benzimidazol-1-yl]hexanoic 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

文献信息

• Discovery of Potent, Selective Chymase Inhibitors via Fragment Linking Strategies
  作者：Steven J. Taylor、Anil K. Padyana、Asitha Abeywardane、Shuang Liang、Ming-Hong Hao、Stéphane De Lombaert、John Proudfoot、Bennett S. Farmer、Xiang Li、Brandon Collins、Leslie Martin、Daniel R. Albaugh、Melissa Hill-Drzewi、Steven S. Pullen、Hidenori Takahashi

  DOI：10.1021/jm400138z

  日期：2013.6.13

  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.