(E)-3-[1-methyl-4-[(E)-3-(2-methylphenyl)-3-oxoprop-1-enyl]pyrrol-2-yl]prop-2-enoic acid | 615252-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-3-[1-methyl-4-[(E)-3-(2-methylphenyl)-3-oxoprop-1-enyl]pyrrol-2-yl]prop-2-enoic acid
• CAS: 615252-69-2
• 化学式: C₁₈H₁₇NO₃
• 分子量: 295.338
• InChiKey: JMDTYEABOOYEDV-FIFLTTCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-[1-methyl-4-[(E)-3-(2-methylphenyl)-3-oxoprop-1-enyl]pyrrol-2-yl]prop-2-enoic acid 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.42h， 生成
  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 氢氧化钾 、 草酰氯 、 potassium carbonate 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 25.25h， 生成 (E)-3-[1-methyl-4-[(E)-3-(2-methylphenyl)-3-oxoprop-1-enyl]pyrrol-2-yl]prop-2-enoic acid
  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 (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.