2-[[3-[(5-bromo-2-oxo-3H-1,3-benzothiazol-7-yl)methyl]-2-oxobenzimidazol-1-yl]methyl]pentanoic acid | 1440806-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-[[3-[(5-bromo-2-oxo-3H-1,3-benzothiazol-7-yl)methyl]-2-oxobenzimidazol-1-yl]methyl]pentanoic acid
• CAS: 1440806-83-6
• 化学式: C₂₁H₂₀BrN₃O₄S
• 分子量: 490.377
• InChiKey: MOWWJKLDGJIOQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴水杨酸 在 偶氮二甲酸二异丙酯 、 硫酸 、 硝酸 、 sodium hydride 、 二异丁基氢化铝 、 三苯基膦 、 tin(ll) chloride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 甲醇 、 乙醚 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 88.17h， 生成 2-[[3-[(5-bromo-2-oxo-3H-1,3-benzothiazol-7-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

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
• [EN] BENZIMIDAZOLONE CHYMASE INHIBITORS<br/>[FR] INHIBITEURS DE BENZIMIDAZOLONE CHYMASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2008147697A1

  公开（公告）日：2008-12-04

  [EN] Disclosed are small molecule inhibitors which are useful in treating various diseases and conditions involving chymase.
  [FR] L'invention concerne des inhibiteurs à petites molécules qui sont utiles dans le traitement de diverses maladies et affections impliquant la chymase.
• 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.