1-(3-methoxybenzyl)-1H-pyrrole-2-carbaldehyde

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(3-methoxybenzyl)-1H-pyrrole-2-carbaldehyde
• 英文别名: 1-(3-methoxybenzyl) pyrrole-2-carboxaldehyde；1-[(3-Methoxyphenyl)methyl]pyrrole-2-carbaldehyde
• 化学式: C₁₃H₁₃NO₂
• 分子量: 215.252
• InChiKey: MQRDEHJWMMOIOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3-methoxybenzyl)-1H-pyrrole-2-carbaldehyde 在 sodium ethanolate 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Diketo Acids Derivatives as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and the Reverse Transcriptase RNase H Domain

  摘要：

  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。

  DOI：

  10.2174/092986711796504619
• 作为产物：
  描述：

  2-吡咯甲醛 、 3-甲氧基溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.25h， 以90%的产率得到1-(3-methoxybenzyl)-1H-pyrrole-2-carbaldehyde
  参考文献：
  名称：

  从 2-甲酰吡咯异吲哚并和吡咯并稠合的多环吲哚的不同合成中的高选择性 Diels-Alder 和 Heck 芳基化反应。

  摘要：

  本文描述了异吲哚并和吡咯并稠合的多环吲哚的高度区域选择性、化学选择性和立体选择性发散合成，从2-甲酰吡咯开始并采用Diels-Alder和Heck芳基化反应。3-( N-苄基-2-吡咯基)丙烯酸酯和4-(吡咯-2-基)丁烯酮与马来酰亚胺进行高度内切狄尔斯-阿尔德环加成反应，得到八氢吡咯并[3,4- e ]吲哚，作为前体通过分子内 Heck 芳基化反应进行氮杂多环骨架的区域选择性合成。通过后一个反应，3-( N-苄基-2-吡咯基)丙烯酸酯产生3-(吡咯并[2,1- a ]异吲哚-3-基)丙烯酸酯。多环中间体的进一步氧化芳构化提供相应的多环吡咯并-异吲哚和异吲哚并-吡咯并-吲哚。通过计算内切/外切过渡态进行的立体选择性狄尔斯-阿尔德反应的理论研究揭示了非共价相互作用在控制内切立体控制中的帮助。

  DOI：

  10.3762/bjoc.16.113

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。
• 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
• Design, synthesis and biological evaluation of heteroaryl diketohexenoic and diketobutanoic acids as HIV-1 integrase inhibitors endowed with antiretroviral activity
  作者：R. Di Santo、R. Costi、M. Artico、R. Ragno、G. Greco、E. Novellino、C. Marchand、Y. Pommier

  DOI：10.1016/j.farmac.2005.03.008

  日期：2005.5

  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.
• Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole
  作者：Carlos H Escalante、Eder I Martínez-Mora、Carlos Espinoza-Hicks、Alejandro A Camacho-Dávila、Fernando R Ramos-Morales、Francisco Delgado、Joaquín Tamariz

  DOI：10.3762/bjoc.16.113

  日期：——

  chemo- and stereoselective divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels–Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels–Alder cycloaddition with maleimides to furnish octahydropyrrolo[3,4-e]indoles, which served as precursors in the

  本文描述了异吲哚并和吡咯并稠合的多环吲哚的高度区域选择性、化学选择性和立体选择性发散合成，从2-甲酰吡咯开始并采用Diels-Alder和Heck芳基化反应。3-( N-苄基-2-吡咯基)丙烯酸酯和4-(吡咯-2-基)丁烯酮与马来酰亚胺进行高度内切狄尔斯-阿尔德环加成反应，得到八氢吡咯并[3,4- e ]吲哚，作为前体通过分子内 Heck 芳基化反应进行氮杂多环骨架的区域选择性合成。通过后一个反应，3-( N-苄基-2-吡咯基)丙烯酸酯产生3-(吡咯并[2,1- a ]异吲哚-3-基)丙烯酸酯。多环中间体的进一步氧化芳构化提供相应的多环吡咯并-异吲哚和异吲哚并-吡咯并-吲哚。通过计算内切/外切过渡态进行的立体选择性狄尔斯-阿尔德反应的理论研究揭示了非共价相互作用在控制内切立体控制中的帮助。
• 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。