2-(2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl)pentanoic acid ethyl ester | 1440807-74-8

• 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-(2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl)pentanoic acid ethyl ester
• CAS: 1440807-74-8
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: VPBYRYJFXCQJFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.31
• 重原子数：
  20.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  64.09
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  6-bromo-4-hydroxymethylindole-1-carboxylic acid tert-butyl ester 、 2-(2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl)pentanoic acid ethyl ester 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以57%的产率得到6-bromo-4-[3-(2-ethoxycarbonylpentyl)-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