4-苯甲酰基-1H-吡咯-2-甲醛 | 15373-02-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-苯甲酰基-1H-吡咯-2-甲醛
• 英文名称: 4-benzoyl-1H-pyrrole-2-carboxaldehyde
• 英文别名: 4-benzoyl-1H-pyrrole-2-carbaldehyde；4-benzoyl-pyrrole-2-carbaldehyde
• CAS: 15373-02-1
• 化学式: C₁₂H₉NO₂
• 分子量: 199.209
• InChiKey: DELNBXZVESYYAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-苯甲酰基-1H-吡咯-2-甲醛 在 palladium on activated charcoal 作用下， 以68%的产率得到3-苯甲酰吡咯
  参考文献：
  名称：

  Anderson, Hugh J.; Loader, Charles E.; Foster, Aidan, Canadian Journal of Chemistry, 1980, vol. 58, p. 2527 - 2530

  摘要：

  DOI：
• 作为产物：
  描述：

  2-吡咯甲醛 、 苯甲酰氯 在 aluminum (III) chloride 作用下， 反应 3.4h， 生成 4-苯甲酰基-1H-吡咯-2-甲醛
  参考文献：
  名称：

  终端脱氧核苷酸转移酶的新型核苷酸竞争性非核苷抑制剂：发现，表征和晶体结构与目标复杂。

  摘要：

  末端脱氧核糖核酸转移酶（TdT）在某些类型的癌症中过表达，在通过非同源末端连接（NHEJ）途径诱变修复双链断裂（DSB）的过程中，末端脱氧核糖核酸转移酶可能与polμ竞争。在这里我们报告发现和表征的吡咯基和吲哚基二酮酸，专门针对TdT和表现为核苷酸竞争性抑制剂。与HeLa细胞相比，这些化合物对MOLT-4具有选择性毒性，而HeLa细胞与TdT的体外选择性密切相关。通过与TdT共结晶确定了这两种抑制剂的结合位点，从而解释了为什么这些化合物是脱氧核苷酸三磷酸（dNTP）的竞争性抑制剂。此外，由于观察到的苯基取代基的双重定位，

  DOI：

  10.1021/jm4010187

文献信息

• Access to 6-hydroxy indolizines and related imidazo[1,5-<i>a</i>]pyridines through the S_N2 substitution/condensation/tautomerization cascade process
  作者：Guiyun Duan、Hao Liu、Liqing Zhang、Chunhao Yuan、Yongchao Li、Yanqing Ge

  DOI：10.1039/d1ra04425g

  日期：——

  A simple and efficient cascade reaction was developed for the construction of hydroxy substituted indolizines from pyrrole-2-carbaldehydes and commercially available 4-halogenated acetoacetic esters. Their optical properties were also evaluated.

  开发了一种简单有效的级联反应，用于从 pyrrole-2-carbaldehydes 和市售的 4-卤代乙酰乙酸酯构建羟基取代的中氮茚。还评估了它们的光学特性。
• Synthesis of 7-cyanoindolizine derivatives via a tandem reaction
  作者：Xian-Sheng Zhang、Bin Wang、Jiong Jia、Yan-Qing Ge、Jianwu Wang

  DOI：10.1515/hc-2016-0223

  日期：2017.4.1

  Abstract: A series of 2-substituted and 2,3-disubstituted 5-cyanoindolizine derivatives were conveniently synthesized by a one-pot tandem reaction under mild conditions in moderate yields. The reaction mechanism was proposed.

  摘要：通过一锅串联反应在温和条件下以中等产率方便地合成了一系列 2-取代和 2,3-二取代 5-氰基茚茚衍生物。提出了反应机理。
• The synthesis, characterization and optical properties of novel 2-acyl 6-arylindolizines
  作者：Yan Qing Ge、Xue Yong Gong、Guang Jie Song、Xiao Qun Cao、Jian Wu Wang

  DOI：10.1016/j.saa.2014.06.146

  日期：2015.1

  A series of novel 2-acyl-6-aryl substituted indolizine derivatives was synthesized by a novel tandem reaction between 4-acyl-pyrrole-2-carbaldehyde derivatives and ethyl 4-bromo-3-arylbut-2-enoate under mild conditions. The compounds were characterized using IR, H-1 NMR C-13 NMR and HRMS. The crystal structure of 7a was determined using single crystal X-ray crystallography. The absorption results showed that compounds 7a-e presented their absorption maxima at ca. 270 nm, while compounds 7f and 7g with a larger conjugation system exhibited red-shifted absorption character (ca. 280 nm). Fluorescence spectra revealed that these compounds exhibited blue fluorescence (434-456 nm) in dilute solutions and showed quantum yields of fluorescence between 0.02 and 0.39 in dichloromethane. (C) 2014 Elsevier B.V. All rights reserved.
• Lehr, Matthias, Journal of Medicinal Chemistry, 1997, vol. 40, # 21, p. 3381 - 3392
  作者：Lehr, Matthias

  DOI：——

  日期：——
• 3-(4-Aroyl-1-methyl-1<i>H</i>-2-pyrrolyl)-<i>N</i>-hydroxy-2-alkylamides as a New Class of Synthetic Histone Deacetylase Inhibitors. 1. Design, Synthesis, Biological Evaluation, and Binding Mode Studies Performed through Three Different Docking Procedures
  作者：Antonello Mai、Silvio Massa、Rino Ragno、Ilaria Cerbara、Florian Jesacher、Peter Loidl、Gerald Brosch

  DOI：10.1021/jm021070e

  日期：2003.2.1

  Recently we reported a novel series of hydroxamates, called 3-(4-aroyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides (APHAs), acting as HDAC inhibitors (Massa, S.; et al. J. Med. Chem. 2001, 44, 2069-2072). Among them, 3-(4-benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide 1 was chosen as lead compound, and its binding mode into the modeled HDAC1 catalytic core together with its histone hyperacetylation, antiproliferative, and cytodifferentiating properties in cell-based assays were investigated (Mai, A.; et al. J. Med. Chem. 2002, 45, 1778-1784). Here we report the results of some chemical manipulations performed on (i) the aroyl portion at the C-4-pyrrole position, (ii) the N-1-pyrrole substituent, and (iii) the hydroxamate moiety of 1 to determine structure-activity relationships and to improve enzyme inhibitory activity of APHAs. In the 1 structure, pyrrole N-1-substitution with groups larger than methyl gave a reduction in HDAC inhibiting activity, and replacement of hydroxamate function with various non-hydroxamate, metal ion-complexing groups yielded poorly active or totally inactive compounds. On the contrary, proper substitution at the C-4-position favorably affected enzyme inhibiting potency, leading to 8 (IC50 = 0.1 muM) and 9 (IC50 = 1.0 muM) which were 38- and 3.8-fold more potent than 1 in in vitro anti-HD2 assay. Against mouse HDAC1, 8 showed an IC50 = 0.5 muM (IC50 of 1 = 4.9 muM), and also in cell-based assay, 8 was endowed with higher histone hyperacetylating activity than 1, although it was less potent than TSA and SAHA. Such enhancement of inhibitory activity can be explained by the higher flexibility of the pyrrole C-4-substituent of 8 which accounts for a considerably better fitting into the HDAC1 pocket and a more favorable enthalpy ligand receptor energy compared to 1. The enhanced fit allows a closer positioning of 8 hydroxamate moiety to the zinc ion. These findings were supported by extensive docking studies (SAD, DOCK, and Autodock) performed on both APHAs and reference drugs (TSA and SAHA).