1-(4-fluorobenzyl)-1H-pyrrole-2-carboxaldehyde | 883541-16-0

• 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: 1-(4-fluorobenzyl)-1H-pyrrole-2-carboxaldehyde
• 英文别名: N-4-fluorobenzylpyrrole-2-carbonylaldehyde；(4-flurobenzyl)pyrrole-2-carboxaldehyde；1-(4-Fluoro-benzyl)-1H-pyrrole-2-carbaldehyde；1-[(4-fluorophenyl)methyl]pyrrole-2-carbaldehyde
• CAS: 883541-16-0
• 化学式: C₁₂H₁₀FNO
• 分子量: 203.216
• InChiKey: NZOPVHUCSSOQEW-UHFFFAOYSA-N

物化性质

• 沸点：
  322.4±22.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  1-(4-fluorobenzyl)-1H-pyrrole-2-carboxaldehyde 在 sodium hydroxide 、 sodium ethanolate 作用下， 反应 27.25h， 生成 (E)-6-[1-(4-Fluoro-benzyl)-1H-pyrrol-2-yl]-2,4-dioxo-hex-5-enoic acid
  参考文献：
  名称：

  6-Aryl-2,4-dioxo-5-hexenoic acids, novel integrase inhibitors active against HIV-1 multiplication in cell-based assays

  摘要：

  A series of 6-aryl-2,4-dioxo-5-hexenoic acids, were synthesized and tested against HIV-1 in cell-based assays and against recombinant HIV-1 integrase (rIN) in enzyme assays. Compound 8a showed potent antiretroviral activity (EC50 = 1.5 muM) and significant inhibition against rIN (strand transfer: IC50 = 7.9 muM; 3'-processing: IC50 = 7.0 muM). A preliminary molecular modeling study was carried out to compare the spatial conformation of 8a with those of L-731,988 (4) and 5CITEP (7) in the IN core. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.037
• 作为产物：
  描述：

  2-吡咯甲醛 、 4-氟溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以98 %的产率得到1-(4-fluorobenzyl)-1H-pyrrole-2-carboxaldehyde
  参考文献：
  名称：

  通过涉及吡咯酰基自由基的氧化酰胺化，从吡咯甲醛和甲酰胺/胺发散合成吡咯甲酰胺

  摘要：

  本文报道了一种由吡咯甲醛和甲酰胺或胺以催化量的n Bu 4 NI和TBHP作为氧化剂合成吡咯甲酰胺的非传统方法。该方法操作简单，可在温和条件下利用廉价试剂以良好至优异的产率直接获得伯、仲和叔吡咯甲酰胺。与涉及离子反应的传统酰胺化不同，我们当前方法的机理研究揭示了 2- 或 3-吡咯酰基自由基的参与，否则很少假设。本方法的适用性在类药物化合物，即光学纯的碳依托咪酯酰胺的合成中得到进一步证明。

  DOI：

  10.1039/d3cc02766j

文献信息

• Design, synthesis and biological evaluation of matrine derivatives as potential anticancer agents
  作者：Zheng Li、Mengyang Luo、Bin Cai、Lichuan Wu、Mengtian Huang、Haroon-Ur-Rashid、Jun Jiang、Lisheng Wang

  DOI：10.1016/j.bmcl.2018.01.017

  日期：2018.2

  Using matrine (1) as the lead compound, a series of new 14-(N-substituted-2-pyrrolemethylene) matrine and 14-(N-substituted-indolemethylene) matrine derivatives was designed and synthesized for their potential application as anticancer agents. The structure of these compounds was characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity

  以苦参碱（1）为先导化合物，设计合成了一系列新的14-（N-取代-2-吡咯亚甲基）苦参碱和14-（N-取代-吲哚亚甲基）苦参碱衍生物，作为其潜在的抗癌剂。这些化合物的结构通过1 H NMR，13 C NMR和ESI-MS光谱分析进行表征。评价目标化合物对三种人类癌细胞系（SMMC-7721，A549和CNE2）的体外细胞毒性。结果显示，化合物A6和B21对具有IC 50的三种癌细胞系表现出最显着的抗癌活性值在3.42-8.05μM范围内，显示出比母体化合物（苦参碱）和阳性对照顺铂更好的活性。此外，膜联蛋白V-FITC / PI双重染色试验表明，化合物A6和B21可以剂量依赖性显着诱导SMMC-7721和CNE2细胞的凋亡。细胞周期分析还表明，化合物A6可导致SMMC-7721和CNE2细胞在G2 / M期的细胞周期停滞。
• Diketo Acids Derivatives as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and the Reverse Transcriptase RNase H Domain
  作者：R. Di Santo

  DOI：10.2174/092986711796504619

  日期：2011.8.1

  The HIV-1 integrase (IN) and reverse transcriptase (RT) are essential enzymes in the virus cycle. RT is crucial for the retrotranscription of the RNA viral genome, while IN is involved in the insertion in host chromosome of the proviral double strand DNA produced by RT. This enzyme has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H (RNase H). The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. Since the discovery that catalytic cores of both HIV-1 RNase H and IN are folded in a very similar way, have very similar active site geometries, and show the same DDE triad absolutely required for catalytic activity, some researches were devoted to study IN and RNase H dual inhibitor. Our decennial interest in design and synthesis of IN inhibitors led us to study the activity of our compounds also on RNase H activity. The results of the activities showed by pyrrolyl and quinolonyl diketo acids are reported and discussed.

  HIV-1 整合酶（IN）和逆转录酶（RT）是病毒循环中的重要酶。RT 对 RNA 病毒基因组的逆转录至关重要，而 IN 则参与将 RT 产生的前病毒双链 DNA 插入宿主染色体。这种酶有两种相关功能：RNA 和 DNA 依赖性 DNA 聚合酶（RDDP 和 DDDP）以及核糖核酸酶 H（RNase H）。RNase H 的功能是催化选择性水解 RNA:DNA 异源双工复制中间体的 RNA 链。自从发现 HIV-1 RNase H 和 IN 的催化核心以非常相似的方式折叠，具有非常相似的活性位点几何结构，并显示出催化活性绝对需要的相同 DDE 三元组之后，一些研究人员致力于 IN 和 RNase H 双抑制剂的研究。我们对 IN 抑制剂的设计和合成有着长达十年的兴趣，这促使我们研究我们的化合物对 RNase H 的活性。报告和讨论了吡咯基和醌基二酮酸的活性结果。
• Design, synthesis, biological evaluation and structure-activity relationship of sophoridine derivatives bearing pyrrole or indole scaffold as potential antitumor agents
  作者：Zheng Li、Mengyang Luo、Bin Cai、Haroon-Ur-Rashid、Mengtian Huang、Jun Jiang、Lisheng Wang、Lichuan Wu

  DOI：10.1016/j.ejmech.2018.08.021

  日期：2018.9

  Taking sophoridine as a lead compound, 58 sophoridine derivatives were designed, synthesized and evaluated for their antiproliferative activity in the HepG2 cancer cell line. Among the 58 compounds, 33 compounds showed potent antiproliferative activity with IC50 less than 10 μM. Compound 5w showed the most potent anti-proliferative activity in the HepG2 cancer cell line. Thus, we further extended our

  以槐定碱为先导化合物，设计，合成并评价了58种槐定碱衍生物在HepG2癌细胞系中的抗增殖活性。在58种化合物中，有33种化合物显示出有效的抗增殖活性，IC 50小于10μM。化合物5w在HepG2癌细胞系中显示出最有效的抗增殖活性。因此，我们进一步扩展了在6种癌细胞系（HepG2，SMMC-7721，Hela，CNE1，CNE2和MCF7）中5w的抗增殖活性的表征。代表性化合物5w在所有测试的具有IC 50的细胞系中均显示出强大的抗增殖活性值在0.93-1.89μM之间，远低于槐定啶。在这里，我们报道了槐定碱系列化合物的构效关系（SAR），这表明在槐定啶的14个碳原子上引入N-苄基吲哚基团可以显着增强抗增殖活性。通过分子对接和酶促测定，发现化合物5w能够抑制DNA Topo I的活性。此外，凋亡测定表明，化合物5w通过激活caspase-3可以剂量依赖性显着诱导HepG2细胞凋亡。 ，增加
• Direct access to pyrrole anhydrides <i>via</i> oxidative self-coupling of pyrrole carboxaldehydes
  作者：Surabhi Panday、Tapas Maity、Pratibha Bhatti、Joydev K. Laha

  DOI：10.1039/d4ob00052h

  日期：2024.4.17

  addition, a one-pot synthesis of novel pyrrole-2-carboxamides from pyrrole-2-carboxaldehydes is also reported. The mechanistic investigation supports a previously unexplored oxidative self-coupling of a pyrrole acyl radical, leading to the synthesis of a carboxylic anhydride.

  本文描述了使用TBAI作为催化剂和叔丁基过氧化氢(TBHP)作为氧化剂从吡咯-2-甲醛合成吡咯-2-羧酸酐。与之前报道中总是使用吡咯-2-羧酸不同，我们在这里首次报道了N-苄基吡咯-2-甲醛的氧化自偶联用于合成1-benzyl- 1H -pyrrole-2-羧酸酐。此外，还报道了从吡咯-2-甲醛一锅法合成新型吡咯-2-甲酰胺。机理研究支持了先前未探索的吡咯酰基自由基的氧化自偶联，从而导致了羧酸酐的合成。
• 6-(1-Benzyl-1<i>H</i>-pyrrol-2-yl)-2,4-dioxo-5-hexenoic Acids as Dual Inhibitors of Recombinant HIV-1 Integrase and Ribonuclease H, Synthesized by a Parallel Synthesis Approach
  作者：Roberta Costi、Mathieu Métifiot、Francesca Esposito、Giuliana Cuzzucoli Crucitti、Luca Pescatori、Antonella Messore、Luigi Scipione、Silvano Tortorella、Luca Zinzula、Ettore Novellino、Yves Pommier、Enzo Tramontano、Christophe Marchand、Roberto Di Santo

  DOI：10.1021/jm401040b

  日期：2013.11.14

  The increasing efficiency of HAART has helped to transform HIV/AIDS into a chronic disease. Still, resistance and drug drug interactions warrant the development of new anti-HIV agents. We previously discovered hit 6, active against HIV-1 replication and targeting RNase H in vitro. Because of its diketo-acid moiety, we speculated that this chemotype could serve to develop dual inhibitors of both RNase H and integrase. Here, we describe a new series of 1-benzyl-pyrrolyl diketohexenoic derivatives, 7a-y and 8a-y, synthesized following a parallel solution-phase approach. Those 50 analogues have been tested on recombinant enzymes (RNase H and integrase) and in cell-based assays. Approximately half (22) exibited inhibition of HIV replication. Compounds 7b, 7u, and 8g were the most active against the RNase H activity of reverse-transcriptase, with IC50 values of 3, 3, and 2.5 mu M, respectively. Compound 8g was also the most potent integrase inhibitor with an IC50 value of 26 nM.