3-(5-oxo-4,5-dihydro[1,2,4]oxadiazol-3-yl)benzenesulfonyl chloride | 476362-72-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5-oxo-4,5-dihydro[1,2,4]oxadiazol-3-yl)benzenesulfonyl chloride
• 英文别名: 3-(5-oxo-4H-1,2,4-oxadiazol-3-yl)benzenesulfonyl chloride
• CAS: 476362-72-8
• 化学式: C₈H₅ClN₂O₄S
• 分子量: 260.658
• InChiKey: PKRZTMSNNBFTST-UHFFFAOYSA-N

物化性质

• 密度：
  1.77±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  93.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(5-oxo-4,5-dihydro[1,2,4]oxadiazol-3-yl)benzenesulfonyl chloride 、 5-((((9H-fluoren-9-yl)methoxy)carbonylamino)methyl)thiophene-2-carboxylic acid 、 5-(2-chloro-benzylsulfanyl)-3(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-pentanoic acid tert-butyl ester 以3.4 mg的产率得到(S)-5-(2-chloro-benzylsulfanyl)-4-oxo-3-[(5-{[3-(5-oxo-2,5-dihydro[1,2,4]-oxadiazol-3-yl)benzenesulfonylamino]methyl}thiophene-2-carbonyl)amino]pentanoic acid
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j
• 作为产物：
  描述：

  tert-butyl (3-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl)carbamate 在 盐酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.25h， 生成 3-(5-oxo-4,5-dihydro[1,2,4]oxadiazol-3-yl)benzenesulfonyl chloride
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j