ethyl 3-(4-formyl-1-methyl-1H-pyrrol-2-yl)-2-propenoate | 615252-64-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 3-(4-formyl-1-methyl-1H-pyrrol-2-yl)-2-propenoate
• 英文别名: ethyl (E)-3-(4-formyl-1-methylpyrrol-2-yl)prop-2-enoate
• CAS: 615252-64-7
• 化学式: C₁₁H₁₃NO₃
• 分子量: 207.229
• InChiKey: NMRLATUVLJJHNP-SNAWJCMRSA-N

物化性质

• 沸点：
  356.8±32.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-formyl-1-methyl-1H-pyrrol-2-yl)-2-propenoate 在 氢氧化钾 、 Amberlyst 15 ion-exchange resin 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 25.42h， 生成 N-hydroxy-3-(1-methyl-4-(3-oxo-3-m-tolylprop-1-enyl)-1H-pyrrol-2-yl)acrylamide
  参考文献：
  名称：

  Class II (IIa)-Selective Histone Deacetylase Inhibitors. 1. Synthesis and Biological Evaluation of Novel (Aryloxopropenyl)pyrrolyl Hydroxyamides

  摘要：

  Chemical manipulations performed on aroyl-pyrrolyl-hydroxyamides (APHAs) led to (aryloxopropenyl)pyrrolyl hydroxamates 2a-w, and their inhibition against maize HDACs and their class I or class II HDAC selectivity were determined. In particular, from these studies some benzene meta-substituted compounds emerged as highly class II (IIa)-selective HDAC inhibitors, the most selective being the 3-chloro- and 3-fluoro-substituted compounds 2c (SI = 71.4) and 2f (SI = 176.4). The replacement of benzene with a 1-naphthyl ring afforded 2s, highly active against the class II homologue HD1-A (IC50 = 10 nM) but less class II-selective than 2c,f When tested against human HDAC1 and HDAC4, 2f showed no inhibitory activity against HDAC1 but was able to inhibit HDAC4. Moreover, in human U937 acute myeloid leukaemia cells 2f did not produce any effect on apoptosis, granulocytic differentiation, and the cell cycle, whereas 2s (that retain class I HDAC inhibitory activity) was 2-fold less potent than SAHA used as reference.

  DOI：

  10.1021/jm049002a
• 作为产物：
  描述：

  N-甲基-2-吡咯甲醛 在 草酰氯 、 potassium carbonate 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 1.25h， 生成 ethyl 3-(4-formyl-1-methyl-1H-pyrrol-2-yl)-2-propenoate
  参考文献：
  名称：

  Discovery of (Aryloxopropenyl)pyrrolyl Hydroxyamides as Selective Inhibitors of Class IIa Histone Deacetylase Homologue HD1-A

  摘要：

  Chemical manipulations performed on aroyl pyrrolyl hydroxyamides, a new class of HDAC inhibitors previously reported by us, led to (aryloxopropenyl)pyrrolyl hydroxyamides 3a-g. Such compounds, showing better inhibitory activity against maize HD1-A than HD1-B (two homologues of mammalian class IIa and I HDACs, respectively), are the first class of Ha-selective inhibitors (fold selectivity: 7-78). They could be useful as tools for probing the biology of these enzymes and eventually as new anticancer agents with low toxicity.

  DOI：

  10.1021/jm034167p

文献信息

• Class II-selective histone deacetylase inhibitors. Part 2: Alignment-independent GRIND 3-D QSAR, homology and docking studies
  作者：Rino Ragno、Silvia Simeoni、Dante Rotili、Antonella Caroli、Giorgia Botta、Gerald Brosch、Silvio Massa、Antonello Mai

  DOI：10.1016/j.ejmech.2007.05.004

  日期：2008.3

  (Aryloxopropenyl)pyrrolyl hydroxamates were recently reported by us as first examples of class H-selective HDAC inhibitors and can be useful tools to probe the biology of such enzymes. Molecular modelling and 3-D QSAR studies have been performed on a series of 25 (aryloxopropenyl)pyrrolyl hydroxamates to gain insights about their activity and selectivity against both maize HD1-B and HD1-A, two enzymes homologous of mammalian class I and class II HDACs, respectively. The studies have been accomplished by calculating alignment-independent descriptors (GRIND descriptors) using the ALMOND software. Highly descriptive and predictive 3-D QSAR models were obtained using either class I or class II inhibitory activity displaying r(2)/q(2) values of 0.96/0.81 and 0.98/0.85 for HD1-B and HD1-A, respectively. A deeper inspection revealed that in general a bent molecular shape structure is a prerequisite for HD1-A-selective inhibitory activity, while straight shape molecular skeleton leads to selective HD1-B compounds. The same conclusions could be achieved by molecular docking studies of the most selective inhibitors. (c) 2007 Elsevier Masson SAS. All rights reserved.

  (Aryloxopropenyl)pyrrolyl羟肟酸类化合物 recently reported by us are the first examples of class H-selective HDAC inhibitors and can serve as useful tools to investigate the biology of such enzymes. A series of 25 (aryloxopropenyl)pyrrolyl羟肟酸类 compounds were subjected to molecular modeling and 3-D QSAR studies to gain insights into their activity and selectivity against maize HD1-B and HD1-A, enzymes homologous to mammalian class I and class II HDACs, respectively. These studies were conducted using alignment-independent descriptors (GRIND descriptors) calculated with the ALMOND software. Highly descriptive and predictive 3-D QSAR models were obtained for both class I and class II inhibitory activities, with r²/q² values of 0.96/0.81 for HD1-B and 0.98/0.85 for HD1-A. Further analysis revealed that a bent molecular structure is generally a prerequisite for HD1-A-selective inhibition, while straight molecular skeletons lead to HD1-B-selective compounds. These conclusions were corroborated by molecular docking studies of the most selective inhibitors. (c) 2007 Elsevier Masson SAS. All rights reserved.
• Class II (IIa)-Selective Histone Deacetylase Inhibitors. 1. Synthesis and Biological Evaluation of Novel (Aryloxopropenyl)pyrrolyl Hydroxyamides
  作者：Antonello Mai、Silvio Massa、Riccardo Pezzi、Silvia Simeoni、Dante Rotili、Angela Nebbioso、Annamaria Scognamiglio、Lucia Altucci、Peter Loidl、Gerald Brosch

  DOI：10.1021/jm049002a

  日期：2005.5.1

  Chemical manipulations performed on aroyl-pyrrolyl-hydroxyamides (APHAs) led to (aryloxopropenyl)pyrrolyl hydroxamates 2a-w, and their inhibition against maize HDACs and their class I or class II HDAC selectivity were determined. In particular, from these studies some benzene meta-substituted compounds emerged as highly class II (IIa)-selective HDAC inhibitors, the most selective being the 3-chloro- and 3-fluoro-substituted compounds 2c (SI = 71.4) and 2f (SI = 176.4). The replacement of benzene with a 1-naphthyl ring afforded 2s, highly active against the class II homologue HD1-A (IC50 = 10 nM) but less class II-selective than 2c,f When tested against human HDAC1 and HDAC4, 2f showed no inhibitory activity against HDAC1 but was able to inhibit HDAC4. Moreover, in human U937 acute myeloid leukaemia cells 2f did not produce any effect on apoptosis, granulocytic differentiation, and the cell cycle, whereas 2s (that retain class I HDAC inhibitory activity) was 2-fold less potent than SAHA used as reference.
• Discovery of (Aryloxopropenyl)pyrrolyl Hydroxyamides as Selective Inhibitors of Class IIa Histone Deacetylase Homologue HD1-A
  作者：Antonello Mai、Silvio Massa、Riccardo Pezzi、Dante Rotili、Peter Loidl、Gerald Brosch

  DOI：10.1021/jm034167p

  日期：2003.11.1

  Chemical manipulations performed on aroyl pyrrolyl hydroxyamides, a new class of HDAC inhibitors previously reported by us, led to (aryloxopropenyl)pyrrolyl hydroxyamides 3a-g. Such compounds, showing better inhibitory activity against maize HD1-A than HD1-B (two homologues of mammalian class IIa and I HDACs, respectively), are the first class of Ha-selective inhibitors (fold selectivity: 7-78). They could be useful as tools for probing the biology of these enzymes and eventually as new anticancer agents with low toxicity.