5-benzoyl-1-methyl-1H-pyrrole-2-carbaldehyde | 676599-93-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-benzoyl-1-methyl-1H-pyrrole-2-carbaldehyde
• 英文别名: 5-Benzoyl-1-methylpyrrole-2-carbaldehyde
• CAS: 676599-93-2
• 化学式: C₁₃H₁₁NO₂
• 分子量: 213.236
• InChiKey: WZLJSVNVTCXGPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-benzoyl-1-methyl-1H-pyrrole-2-carbaldehyde 在 氢氧化钾 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 3-(2-benzoyl-1-methyl-1H-pyrrol-5-yl)propenoic acid
  参考文献：
  名称：

  3-(4-Aroyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides as a New Class of Synthetic Histone Deacetylase Inhibitors. 3. Discovery of Novel Lead Compounds through Structure-Based Drug Design and Docking Studies^,

  摘要：

  Aroyl-pyrrole-hydroxy-amides (APHAs) are a new class of synthetic HDAC inhibitors recently described by us. Through three different docking procedures we designed, synthesized, and tested two new isomers of APHA lead compound 3-(4-benzoyl-l-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (1), compounds 3 and 4, characterized by different insertions of benzoyl and propenoylhydroxamate groups onto the pyrrole ring. Biological activities of 3 and 4 were predicted by computational tools up to 617-fold more potent than that of I against HDAC1; thus, 3 and 4 were synthesized and tested against both mouse HDAC1 and maize HD2 enzymes. Predictions of biological affinities (K-i values) of 3 and 4, performed by a VALIDATE model (applied on either SAD or automatic DOCK or Autodock results) and by the Autodock internal scoring function, were in good agreement with experimental activities. Ligand/receptor positive interactions made by 3 and 4 into the catalytic pocket, in addition to those showed by 1, could at least in part account for their higher HDAC1 inhibitory activities. In particular, in mouse HDAC1 inhibitory assay 3 and 4 were 19- and 6-times more potent than 1, respectively, and 3 and 4 antimaize HD2 activities were 16- and 76-times higher than that of 1, 4 being as potent as SAHA in this assay. Compound 4, tested as antiproliferative and cytodifferentiating agent.

  DOI：

  10.1021/jm031036f
• 作为产物：
  描述：

  (1-甲基-1H-吡咯-2-基)苯基甲酮 、 乙醛酸 在 dipotassium peroxodisulfate 作用下， 以 乙腈 为溶剂， 以70 %的产率得到5-benzoyl-1-methyl-1H-pyrrole-2-carbaldehyde
  参考文献：
  名称：

  含氮杂环化合物（氮杂吲哚、吲哚、吡咯）和苯胺利用乙醛酸的位点选择性脱羧直接甲酰化

  摘要：

  一种新的氮杂环甲酰化方法克服了使用廉价原料甲酰化剂的经典方法的局限性，特别是在温和和中性条件下，这是当前研究的主题。这项工作描述了使用乙醛酸作为甲酰源和 K 2 S 2 O 8对氮杂环化合物（氮杂吲哚、吲哚、吡咯）和苯胺的直接甲酰化作为独家试剂。关键特征包括在中性和温和反应条件下进行 C- 和 N- 甲酰化的通用方法。该方法在含氮杂环化合物、药物和天然产物的串联合成中的应用进一步得到证实。与用芳基乙醛酸进行的芳酰化不同，现在公开了一种以前未知的在 K 2 S 2 O 8存在下用乙醛酸进行直接甲酰化的途径。

  DOI：

  10.1002/adsc.202201384