1-(2-Methyl-benzyl)-1H-pyrrole-2-carbaldehyde | 946774-66-9

• 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-(2-Methyl-benzyl)-1H-pyrrole-2-carbaldehyde
• 英文别名: 1-[(2-Methylphenyl)methyl]pyrrole-2-carbaldehyde
• CAS: 946774-66-9
• 化学式: C₁₃H₁₃NO
• 分子量: 199.252
• InChiKey: VEBAKUQGNJIJSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(2-Methyl-benzyl)-1H-pyrrole-2-carbaldehyde 在 sodium hydroxide 、 sodium ethanolate 作用下， 以 四氢呋喃 为溶剂， 反应 25.75h， 生成 (E)-6-[1-(2-Methyl-benzyl)-1H-pyrrol-2-yl]-2,4-dioxo-hex-5-enoic acid ethyl ester
  参考文献：
  名称：

  Design, synthesis and biological evaluation of heteroaryl diketohexenoic and diketobutanoic acids as HIV-1 integrase inhibitors endowed with antiretroviral activity

  摘要：

  Highly active anti-retroviral therapy (HAART) using reverse transcriptase (RT) and protease (PR) inhibitors and, more recently, inhibitors of the fusion is currently the best clinical approach in combating acquired immunodeficiency syndrome (AIDS), caused by infection from human immunodeficiency virus type 1 (HIV-1). However, this therapy does not completely eradicate the virus, so that resistant strains easily emerge. The above problem calls urgently for research on inhibitors of further viral targets such as integrase (IN), the third enzyme produced by HIV. Recently, our research group was engaged in studies on conformationally restrained cinnamoyl compounds related to curcumin as anti-IN agents. Compounds containing both a 3,4,5-trihydroxyphenyl group and a carboxylic acid function were potent IN inhibitors active against viral replication. More recently, a promising new class of inhibitors synthesized by Merck Company has emerged, which contain aryldiketoacid (ADK) functionality. The ADKs selectively inhibited the stand transfer (ST) step of integration and were proven to be effective IN inhibitors in vivo. Our interest in the field of IN inhibitors led us to design pyrrole and indole derivatives containing both a cinnamoyl moiety and a diketoacid group. A number of the cited derivatives were proven potent IN inhibitors, which selectively inhibited the ST step at submicromolar concentrations and were effective against virus replication in HIV-1 infected cells.

  DOI：

  10.1016/j.farmac.2005.03.008
• 作为产物：
  描述：

  2-吡咯甲醛 、 2-甲基苄溴 在 sodium hydride 作用下， 以 mineral oil 、 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(2-Methyl-benzyl)-1H-pyrrole-2-carbaldehyde
  参考文献：
  名称：

  NHC催化多环芳基醛的[12+2]反应获得吲哚衍生物

  摘要：

  公开了一种 N-杂环卡宾 (NHC) 催化的对映选择性和非对映选择性 [12+2] 环加成反应，可快速构建带有三环核心和吗啉部分的复杂分子。我们反应的成功依赖于 NHC 催化的远程 sp 3 (C–H) 键在氧化条件下激活 5 H -benzo[ a ]pyrrolizine-3-carbaldehyde。初步研究表明，我们的产品对两种植物病原体的体外生物活性优于商业双硫唑 (BT) 和硫代二唑铜 (TC)。

  DOI：

  10.1039/d3cc00999h

文献信息

• Enantioselective Construction of the Cycl[3.2.2]azine Core via Organocatalytic [12 + 2] Cycloadditions
  作者：Nicolaj Inunnguaq Jessen、Giulio Bertuzzi、Maksimilian Bura、Mette Louise Skipper、Karl Anker Jørgensen

  DOI：10.1021/jacs.1c00499

  日期：2021.4.28

  The developed reaction is robust toward diverse substituent patterns and has been extended to different classes of electron-deficient 2π-components by minor variations in reaction setup. The obtained [12 + 2] cycloadducts are electron-deficient in nature, and their reaction with nucleophiles have been demonstrated. The enantioselective [12 + 2] cycloaddition with α,β-unsaturated aldehydes as the electron-deficient

  第一个对映选择性 [12 + 2] 环加成反应是通过操作简单的一步有机催化过程构建手性环 [3.2.2] 吖嗪核，这是一个具有中心环结氮原子的三环部分。该反应概念建立在氨基催化生成的 12π-组分上，该组分衍生自 5 H-苯并[ a ]吡咯嗪-3-甲醛与不同的缺电子2π-组分反应并提供苯并[ a ]环[3.2.2]嗪的复杂支架(indolizino[3,4,5- ab]异吲哚）具有出色的对映选择性和非对映选择性，收率良好。所开发的反应对不同的取代基模式具有稳健性，并且通过反应设置的微小变化已扩展到不同类别的缺电子 2π 组分。获得的[12+2]环加合物本质上是缺电子的，并且已经证明了它们与亲核试剂的反应。与作为缺电子 2π 组分的 α,β-不饱和醛的对映选择性 [12 + 2] 环加成依赖于非常规的简单氨基催化剂。为了了解这种简单催化剂的 [12 + 2] 环加成的高立体选择性，进行了结合实验和计算研究。研究表明
• 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
• 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.