(Z)-N-[2-oxo-3-({4-oxo-3-[3-oxo-3-(pyrrolidin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl}methylene)indolin-5-yl]benzenesulfonamide | 1239440-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (Z)-N-[2-oxo-3-({4-oxo-3-[3-oxo-3-(pyrrolidin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl}methylene)indolin-5-yl]benzenesulfonamide
• 英文别名: N-[(3Z)-2-oxo-3-[[4-oxo-3-(3-oxo-3-pyrrolidin-1-ylpropyl)-1,5,6,7-tetrahydroindol-2-yl]methylidene]-1H-indol-5-yl]benzenesulfonamide
• CAS: 1239440-78-8
• 化学式: C₃₀H₃₀N₄O₅S
• 分子量: 558.658
• InChiKey: JVXJMEFHHQBIIG-NKFKGCMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  四氢吡咯 、 C₂₉H₂₅N₅O₅S 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 (Z)-N-[2-oxo-3-({4-oxo-3-[3-oxo-3-(pyrrolidin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl}methylene)indolin-5-yl]benzenesulfonamide
  参考文献：
  名称：

  Discovery of Pyrrole−Indoline-2-ones as Aurora Kinase Inhibitors with a Different Inhibition Profile

  摘要：

  A series of pyrrole-indolin-2-ones were synthesized, and their inhibition profile for Aurora kinases was studied. The potent compound 33 with phenylsulfonamido at the C-5 position and a carboxyethyl group at the C-3' position selectively inhibited Aurora A over Aurora B with IC(50) values of 12 and 156 nM, respectively. Replacement of the carboxyl group with an amino group led to compound 47, which retained the activity for Aurora B and lost activity for Aurora A (IC(50) = 2.19 mu M). Computation modeling was used to address the different inhibition profiles of 33 and 47. Compounds 47 and 36 (the ethyl ester analogue of 33) inhibited the proliferation of HCT-116 and HT-29 cells and suppressed levels of the phosphorylated substrates of Aurora A and Aurora B in the Western blots.

  DOI：

  10.1021/jm1001869