6-bromo-2-tert-butoxycarbonyloxy-4-[3-(1-ethoxycarbonylmethylbutyl)-2-oxo-2,3-dihydrobenzoimidazol-1ylmethyl]indole-1-carboxylic acid tert-butyl ester | 1440808-69-4

• 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-2-tert-butoxycarbonyloxy-4-[3-(1-ethoxycarbonylmethylbutyl)-2-oxo-2,3-dihydrobenzoimidazol-1ylmethyl]indole-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 6-bromo-4-[[3-(1-ethoxy-1-oxohexan-3-yl)-2-oxobenzimidazol-1-yl]methyl]-2-[(2-methylpropan-2-yl)oxycarbonyloxy]indole-1-carboxylate；tert-butyl 6-bromo-4-[[3-(1-ethoxy-1-oxohexan-3-yl)-2-oxobenzimidazol-1-yl]methyl]-2-[(2-methylpropan-2-yl)oxycarbonyloxy]indole-1-carboxylate
• CAS: 1440808-69-4
• 化学式: C₃₄H₄₂BrN₃O₈
• 分子量: 700.627
• InChiKey: JPVUOHOANFSTTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-bromo-2-tert-butoxycarbonyloxy-4-[3-(1-ethoxycarbonylmethylbutyl)-2-oxo-2,3-dihydrobenzoimidazol-1ylmethyl]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 0.25h， 以85%的产率得到3-[3-(6-bromo-2-oxo-2,3-dihydro-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-yl]hexanoic 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：

  3,3,6-tribromo-2-oxo-2,3-dihydro-1H-indole-4-carboxylic acid methyl ester 在 4-二甲氨基吡啶 、 偶氮二甲酸二异丙酯 、 二异丁基氢化铝 、 溶剂黄146 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 正庚烷 为溶剂， 反应 9.0h， 生成 6-bromo-2-tert-butoxycarbonyloxy-4-[3-(1-ethoxycarbonylmethylbutyl)-2-oxo-2,3-dihydrobenzoimidazol-1ylmethyl]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