5-{[5-((S)-2-Carboxy-1-formyl-ethylcarbamoyl)-thiophen-3-ylmethyl]-sulfamoyl}-2-hydroxy-benzoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-{[5-((S)-2-Carboxy-1-formyl-ethylcarbamoyl)-thiophen-3-ylmethyl]-sulfamoyl}-2-hydroxy-benzoic acid
• 英文别名: Inhibitor 68a；5-[[5-[[(2S)-1-carboxy-3-oxopropan-2-yl]carbamoyl]thiophen-3-yl]methylsulfamoyl]-2-hydroxybenzoic acid
• 化学式: C₁₇H₁₆N₂O₉S₂
• 分子量: 456.454
• InChiKey: XTYAXJSXJWVVFZ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  224
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-氯磺酰基-2-羟基苯甲酸 、 4-[(9H-Fluoren-9-ylmethoxycarbonylamino)-methyl]-thiophene-2-carboxylic acid 、 alkaline earth salt of/the/ methylsulfuric acid 以17.6 mg的产率得到5-{[5-((S)-2-Carboxy-1-formyl-ethylcarbamoyl)-thiophen-3-ylmethyl]-sulfamoyl}-2-hydroxy-benzoic 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