5-bromo-2-dimethylcarbamoylsulfanyl-3-nitrobenzoic acid ethyl ester | 1090904-00-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-bromo-2-dimethylcarbamoylsulfanyl-3-nitrobenzoic acid ethyl ester
• 英文别名: 5-Bromo-2-dimethylcarbamoylsulfanyl-3-nitro-benzoic acid ethyl ester；ethyl 5-bromo-2-(dimethylcarbamoylsulfanyl)-3-nitrobenzoate
• CAS: 1090904-00-9
• 化学式: C₁₂H₁₃BrN₂O₅S
• 分子量: 377.216
• InChiKey: XDOSCBYKDBNDKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-bromo-2-dimethylcarbamoylsulfanyl-3-nitrobenzoic acid ethyl ester 在 偶氮二甲酸二异丙酯 、 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 、 甲醇 、 乙醚 、 水 、 乙酸乙酯 为溶剂， 反应 7.0h， 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
• 作为产物：
  描述：

  5-溴水杨酸 在 硫酸 、 硝酸 、 sodium hydride 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 81.17h， 生成 5-bromo-2-dimethylcarbamoylsulfanyl-3-nitrobenzoic acid ethyl 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：Abeywardane Asitha

  公开号：US09150556B2

  公开（公告）日：2015-10-06

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

  本发明揭示了一种小分子抑制剂，可用于治疗涉及痰蛋白酶的各种疾病和病况。
• 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.