6-bromo-2-tert-butoxycarbonyloxyindole-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester | 1090903-70-0

• 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-butoxycarbonyloxyindole-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester
• 英文别名: 1-O-tert-butyl 4-O-methyl 6-bromo-2-[(2-methylpropan-2-yl)oxycarbonyloxy]indole-1,4-dicarboxylate
• CAS: 1090903-70-0
• 化学式: C₂₀H₂₄BrNO₇
• 分子量: 470.317
• InChiKey: GLQPNBSVGMYIRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  93.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-bromo-2-tert-butoxycarbonyloxyindole-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正庚烷 为溶剂， 反应 2.0h， 以48%的产率得到6-bromo-2-tert-butoxycarbonyloxy-4-hydroxymethylindole-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
• 作为产物：
  描述：

  6-溴-4-吲哚甲酸甲酯 在 4-二甲氨基吡啶 、 pyridinium hydrobromide perbromide 、 溶剂黄146 、 锌 、 叔丁醇 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 生成 6-bromo-2-tert-butoxycarbonyloxyindole-1,4-dicarboxylic acid 1-tert-butyl ester 4-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

文献信息

• Benzimidazolone Chymase Inhibitors
  申请人：Abeywardane Asitha

  公开号：US20100240702A1

  公开（公告）日：2010-09-23

  Disclosed are small molecule inhibitors which are useful in treating various diseases and conditions involving chymase.

  公开了一种小分子抑制剂，其在治疗涉及chymase的各种疾病和病况方面是有用的。
• BENZIMIDAZOLONE CHYMASE INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2152674B1

  公开（公告）日：2011-08-03
• US9150556B2
  申请人：——

  公开号：US9150556B2

  公开（公告）日：2015-10-06