ethyl 3-(4-oxo-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-3-yl)propanoate | 1239440-92-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 3-(4-oxo-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-3-yl)propanoate
• 英文别名: ethyl 3-(4-oxo-5,6,7,8-tetrahydro-1H-cyclohepta[b]pyrrol-3-yl)propanoate
• CAS: 1239440-92-6
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: PZFGKVPRHUVBFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-oxo-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-3-yl)propanoate 、 原甲酸三甲酯 在 三氟乙酸 作用下， 以19%的产率得到ethyl 3-(2-formyl-4-oxo-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-3-yl)propanoate
  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
• 作为产物：
  描述：

  3-(4-oxo-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-3-yl)propanoic acid 、 乙醇 在 硫酸 作用下， 反应 12.0h， 以99%的产率得到ethyl 3-(4-oxo-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-3-yl)propanoate
  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

文献信息

• Discovery of Pyrrole−Indoline-2-ones as Aurora Kinase Inhibitors with a Different Inhibition Profile
  作者：Chao-Cheng Chiang、Yu-Hsiang Lin、Shu Fu Lin、Chun-Liang Lai、Chiawei Liu、Win-Yin Wei、Sheng-chuan Yang、Ru-Wen Wang、Li-Wei Teng、Shih-Hsien Chuang、Jia-Ming Chang、Ta-Tung Yuan、Ying-Shuen Lee、Paonien Chen、Wei-Kuang Chi、Ju-Ying Yang、Hung-Jyun Huang、Chu-Bin Liao、Jiann-Jyh Huang

  DOI：10.1021/jm1001869

  日期：2010.8.26

  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.