2-[3-(5-bromo-2-oxo-2,3-dihydrobenzothiazol-7-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic acid ethyl ester | 1440809-25-5

• 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-2,3-dihydrobenzothiazol-7-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic acid ethyl ester
• 英文别名: ethyl 2-[[3-[(5-bromo-2-oxo-3H-1,3-benzothiazol-7-yl)methyl]-2-oxobenzimidazol-1-yl]methyl]pentanoate
• CAS: 1440809-25-5
• 化学式: C₂₃H₂₄BrN₃O₄S
• 分子量: 518.431
• InChiKey: KLRIYYKSRQHRBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[3-(5-bromo-2-oxo-2,3-dihydrobenzothiazol-7-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic acid ethyl ester 在 lithium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 以47%的产率得到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 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 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 乙醚 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 87.17h， 生成 2-[3-(5-bromo-2-oxo-2,3-dihydrobenzothiazol-7-ylmethyl)-2-oxo-2,3-dihydrobenzoimidazol-1-ylmethyl]pentanoic 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