ethyl 3-(4-acetyl-2-formyl-5-methyl-1H-pyrrol-3-yl)propanoate | 1239440-76-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 3-(4-acetyl-2-formyl-5-methyl-1H-pyrrol-3-yl)propanoate
• CAS: 1239440-76-6
• 化学式: C₁₃H₁₇NO₄
• 分子量: 251.282
• InChiKey: QTGPAVWOGFHGJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氟吲哚-2-酮 、 ethyl 3-(4-acetyl-2-formyl-5-methyl-1H-pyrrol-3-yl)propanoate 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成
  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：

  ethyl 3-(4-acetyl-5-methyl-1H-pyrrol-3-yl)propanoate 、 原甲酸三甲酯 在 三氟乙酸 作用下， 以21%的产率得到ethyl 3-(4-acetyl-2-formyl-5-methyl-1H-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

• The inhibition profiles of 4'‐acylpyrrole–5‐fluoroindolin‐2‐ones with a C‐3' side chain for VEGFR2, PDGFR‐β, and FGFR‐1 protein kinases
  作者：Jiann‐Jyh Huang、Yu‐Hsiang Lin、Chun‐Liang Lai、Sheng‐Chuan Yang、Shu Fu Lin、Ju‐Ying Yang、Hung‐Jyun Huang、Chiawei Liu、Win‐Yin Wei、Shih‐Hsien Chuang、Chao‐Cheng Chiang、Ying‐Shuen E. Lee、Chu‐Bin Liao、Ching Yuh Chern

  DOI：10.1002/jccs.201900466

  日期：2020.3

  we reported the inhibition profiles of 4′‐acylpyrrole–5‐fluoroindolin‐2‐one 3 with a C‐3′ side chain for VEGFR2, PDGFR‐β, and FGFR‐1 protein kinases. The pyrrole‐fused cyclohexanone moiety provided 3 with the best potency to inhibit the three kinases, and the C‐3′ side chains contributed to the different inhibition profiles of 3. Compound 3b with a C‐3′ 2‐carboxylethyl side chain showed good potency

  在这项研究中，我们报道4'-酰基吡咯-5-氟二氢-2-酮的抑制谱3与C-3'侧链VEGFR2，PDGFR-β，和FGFR-1蛋白激酶。吡咯-稠合的环己酮部分设置3具有抑制三种激酶最好的效力，并促成的不同抑制谱的C-3'侧链3。具有C- 3'2-羧乙基侧链的化合物3b对这三种激酶显示出良好的效价（IC 50：25–260 nM），具有N，N-二烷基-2-氨基甲酰基乙基侧链的化合物3g具有更高的活性。 VEGFR2（IC 50：59纳米）和PDGFR-β（IC 50：16 nM）比FGFR-1（IC 50：1.7μM）。C- 3'3- （二烷基氨基）丙基侧链可作为选择性PDGFR-β抑制剂在3h – j内完成（IC 50：7.8–13 nM）。对化合物3b进行了进一步研究，发现它具有抑制VEGF和FGF依赖性细胞增殖的作用，并具有中等的体内抗癌活性。从对接模拟结果表明的相互作用3B与VEGFR
• 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.