5-(4-Chlorophenyl)-1-cyclopropyl-4-[3-[4-[4-[(4-fluoro-3-nitrophenyl)sulfonylamino]phenyl]piperazin-1-yl]phenyl]-2-methylpyrrole-3-carboxylic acid | 1384513-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-(4-Chlorophenyl)-1-cyclopropyl-4-[3-[4-[4-[(4-fluoro-3-nitrophenyl)sulfonylamino]phenyl]piperazin-1-yl]phenyl]-2-methylpyrrole-3-carboxylic acid
• CAS: 1384513-21-6
• 化学式: C₃₇H₃₃ClFN₅O₆S
• 分子量: 730.216
• InChiKey: MEEKBVKVDMDOMX-UHFFFAOYSA-N

物化性质

• 沸点：
  866.6±75.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  51
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (R)-N¹,N¹-dimethyl-4-(phenylthio)butane-1,3-diamine 、 5-(4-Chlorophenyl)-1-cyclopropyl-4-[3-[4-[4-[(4-fluoro-3-nitrophenyl)sulfonylamino]phenyl]piperazin-1-yl]phenyl]-2-methylpyrrole-3-carboxylic acid 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到(R)-5-(4-chlorophenyl)-1-cyclopropyl-4-(3-(4-(4-(4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

  摘要：

  Bcl-2 and Bcl-xL are key apoptosis regulators and attractive cancer therapeutic targets. We have designed and optimized a class of small-molecule inhibitors of Bcl-2 and Bcl-xL containing a 4,5-diphenyl-1H-pyrrole-3-carboxylic acid core structure. A 1.4 angstrom resolution crystal structure of a lead compound, 12, complexed with Bcl-xL has provided a basis for our optimization. The most potent compounds, 14 and 15, bind to Bcl-2 and Bcl-xL with subnanomolar K-i values and are potent antagonists of Bcl-2 and Bcl-xL in functional assays. Compounds 14 and 15 inhibit cell growth with low nanomolar IC50 values in multiple small-cell lung cancer cell lines and induce robust apoptosis in cancer cells at concentrations as low as 10 nM. Compound 14 also achieves strong antitumor activity in an animal model of human cancer.

  DOI：

  10.1021/jm300608w
• 作为产物：
  描述：

  5-(4-chlorophenyl)-1-cyclopropyl-4-(3-iodophenyl)-2-methyl-1H-pyrrole-3-carboxylic acid 在 吡啶 、 copper(l) iodide 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 L-脯氨酸 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 5-(4-Chlorophenyl)-1-cyclopropyl-4-[3-[4-[4-[(4-fluoro-3-nitrophenyl)sulfonylamino]phenyl]piperazin-1-yl]phenyl]-2-methylpyrrole-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

  摘要：

  Bcl-2 and Bcl-xL are key apoptosis regulators and attractive cancer therapeutic targets. We have designed and optimized a class of small-molecule inhibitors of Bcl-2 and Bcl-xL containing a 4,5-diphenyl-1H-pyrrole-3-carboxylic acid core structure. A 1.4 angstrom resolution crystal structure of a lead compound, 12, complexed with Bcl-xL has provided a basis for our optimization. The most potent compounds, 14 and 15, bind to Bcl-2 and Bcl-xL with subnanomolar K-i values and are potent antagonists of Bcl-2 and Bcl-xL in functional assays. Compounds 14 and 15 inhibit cell growth with low nanomolar IC50 values in multiple small-cell lung cancer cell lines and induce robust apoptosis in cancer cells at concentrations as low as 10 nM. Compound 14 also achieves strong antitumor activity in an animal model of human cancer.

  DOI：

  10.1021/jm300608w