2-methoxy-3-(2-methylpropenyl)-[1,4]naphthoquinone | 870695-92-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-methoxy-3-(2-methylpropenyl)-[1,4]naphthoquinone
• 英文别名: metoxy-norlapachol；2-methoxy-3-(2-methylprop-1-enyl)naphthalene-1,4-dione
• CAS: 870695-92-4
• 化学式: C₁₅H₁₄O₃
• 分子量: 242.274
• InChiKey: ZATSALQNYKNCGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-methoxy-3-(2-methylpropenyl)-[1,4]naphthoquinone 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以63%的产率得到2-amino-3-(2-methyl-propenyl)-[1,4]naphthoquinone
  参考文献：
  名称：

  New 1,2,3,4-tetrahydro-1-aza-anthraquinones and 2-aminoalkyl compounds from norlapachol with molluscicidal activity

  摘要：

  New nitrogen derivatives from norlapachol, including four new diastereomeric 1,2,3,4-tetrahydro-1-aza-anthraquinones obtained from the Prins cyclization on suitable aminoacetaldehyde dimethylacetal derivatives with formic acid, were found to exhibit molluscicidal activity against Biomphalaria glabrata. These derivatives showed low to medium LC50 values, similar to those reported previously for the homologous series of nitrogen derivatives of lapachol. The toxicity profile against Artemia salina was also determined for all compounds. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.068
• 作为产物：
  描述：

  2-羟基-1,4-萘醌 在 potassium carbonate 、 溶剂黄146 、 β-丙氨酸 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 3.0h， 生成 2-methoxy-3-(2-methylpropenyl)-[1,4]naphthoquinone
  参考文献：
  名称：

  使用点击化学方法对2- [氨基烷基-（1H-1,2,3-三唑-1-基）]-1,4-萘醌进行分子多样化的新策略

  摘要：

  基于点击化学的2-氨基-烷基-1,2,3-三唑-1,4-萘醌衍生物合成策略可从1,4-萘醌（1,4-NQ）获得所需的产物，以及生物基的法拉索，去甲拉帕胆和拉帕胆 从1,4-NQ和氨基醇开始的第一条路线（策略A），然后是2-氨基-烷基-1,4-NQ醇，被甲苯磺酸化。叠氮化物离子取代了甲苯磺酸酯基团，得到2-叠氮化物-烷基-1,4-NQ，将其置于铜催化的叠氮化物炔烃环加成（CuAAC）条件下。以大约47％的总产率获得了三唑-萘醌。另一种途径（策略B）使用NaN3作为亲核试剂，依次进行CuAAC取代邻苯二甲酰亚胺，并用肼生成氨基三唑对邻苯二甲酰亚胺基团进行脱保护。随后的反应是，1 4-NQ分四步生产了2-氨基-烷基-1,2,3-三唑-1,4-NQ衍生物，总产率为45-76％。在我们开发了这两种策略之后，选择了线性合成方法（策略A）来制备2-[（（2-（1H-1,2,3-三唑-1-基）乙基氨基）]

  DOI：

  10.21577/0103-5053.20160207

文献信息

• Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity
  作者：Annelise Casellato、Amanda P. Neves、J. Walkimar de M. Carneiro、Maria D. Vargas、Lorenzo do C. Visentin、Alviclér Magalhães、Celso A. Câmara、Claudia Pessoa、Letícia V. Costa-Lotufo、José D. B. Marinho Filho、Manoel O. de Moraes

  DOI：10.1590/s0103-50532010000100024

  日期：——

  Novel 2-(R-phenyl)amino-3-(2-methyl-propenyl)-[1,4]-naphthoquinones (R = H, 4-OMe, 4-Ferrocenyl, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 and 3-NO2) derived from nor-lapachol [2-hydroxy-3-(2-methylpropenyl)-1,4-naphthoquinone] were obtained in good yields. Their structures were proposed on the basis of a single crystal X-ray diffraction study (R = OMe, 2b), ¹H and 13C NMR studies and calculations using the B3LYP functional and the 6-311+G(2d,p) basis set. The half-wave potentials of the aminonaphthoquinones and ¹H NMR chemical shifts of the 3-propenyl hydrogen in 2a-k show good correlation with the substituent Hammett constants on the phenylamino ring. The antitumor assays showed promising activity for substrate methoxy-nor-lapachol 1 and the 4-ferrocenyl derivative 2c.

  从 nor-lapachol [2-羟基-3-(2-甲基丙烯基)-1,4-萘醌] 中获得了新的 2-(R-苯基)氨基-3-(2-甲基丙烯基)-[1,4]-萘醌（R = H、4-OMe、4-二茂铁基、4-Me、3-Me、4-I、3-I、4-CN、3-CN、4-NO2 和 3- ），产量良好。根据单晶 X 射线衍射研究（R = OMe，2b）、¹H 和 13C NMR 研究以及使用 B3LYP 函数和 6-311+G(2d,p) 基集进行的计算，提出了它们的结构。氨基萘醌的半波电位和 2a-k 中 3-丙烯基氢的 ¹H NMR 化学位移显示出与苯胺环上取代基 Hammett 常量的良好相关性。抗肿瘤试验表明，底物甲氧基-去甲-拉帕醌 1 和 4-二茂铁基衍生物 2c 具有良好的活性。
• Conjugation with polyamines enhances the antitumor activity of naphthoquinones against human glioblastoma cells
  作者：Luciana Romão、Vanessa P. do Canto、Paulo A. Netz、Vivaldo Moura-Neto、Ângelo C. Pinto、Cristian Follmer

  DOI：10.1097/cad.0000000000000619

  日期：2018.7

  context, extensive efforts have been undertaken to develop new drugs that exhibit both antiproliferation and antimetastasis effects on GBM. 1,4-Naphthoquinone (1,4-NQ) scaffold has been found in compounds able to inhibit important biological targets associated with cancer, which includes DNA topoisomerase, Hsp90 and monoamine oxidase. Among potential antineoplastic 1,4-NQs is the plant-derived lapachol

  胶质母细胞瘤（GBM）是最常见和最具破坏性的原发性脑肿瘤，被认为是最致命的人类癌症。在这种情况下，已经进行了广泛的努力来开发对GBM表现出抗增殖和抗转移作用的新药。在能够抑制与癌症相关的重要生物学靶标的化合物中发现了1,4-萘醌（1,4-NQ）支架，包括DNA拓扑异构酶，Hsp90和单胺氧化酶。潜在的抗肿瘤药1,4-NQs是植物来源的拉帕胆酚（2-羟基-3-异戊烯基-1,4-萘醌），被发现具有抗Walker-256癌和吉田肉瘤的活性。在本研究中，我们研究了多巴胺，去甲拉帕考和Lawone的多胺（PA）偶联衍生物对人GBM细胞生长和侵袭的影响。与PA（亚精胺类似物）的结合导致1,4-NQs细胞毒性的剂量依赖性和时间依赖性增加。另外，PA结合后增加了拉帕胆酚对GBM细胞入侵的体外抑制作用。先前的生化实验表明，这些PA-1,4-NQs能够抑制DNA人拓扑异构酶II-α（topo2α），这是一种参
• In silico evaluation of the antibacterial and modulatory activity of lapachol and nor-lapachol derivates
  作者：Fernando Gomes Figueredo、Ingrid T.L. Ramos、Josinete A. Paz、Tania M.S. Silva、Celso A. Camara、Cícera Datiane de Morais Oliveira-Tintino、Saulo Relison Tintino、Pablo Antônio Maia de Farias、Henrique Douglas Melo Coutinho、Marta Maria de F. Fonteles

  DOI：10.1016/j.micpath.2020.104181

  日期：2020.7

  the Minimum Inhibitory Concentration (MIC). The molecular structures were analyzed using the ChEMBL database to predict possible pharmacological targets, which pointed to the molecule 2- (2-hydroxy-ethylamine)-3-(2-methyl-propenyl)-[1,4]naphthoquinone as a probable antibacterial agent for the proteins Replicative DNA helicase and RecA. The compounds had a low molecular weight and a small number of rotatable

  这项研究的目的是调查2-（2-羟乙胺）-3-（3-甲基-2-丁烯基）-1,4-二氢-1,4-萘二酮，2-（2-羟基-乙胺）-3-（2-甲基丙烯基）-[1,4]萘醌和2-（3-羟基丙胺）-3-（3-甲基-2-丁烯基）-[1,4]萘醌计算预测模型，以及评估这些化合物对细菌ATCC菌株和临床分离株的体外抗菌和调节活性。由2-羟基醌，拉帕胆和正拉帕胆合成这些物质，在碱性介质中通过硫酸二甲酯烷基化得到相应的2-甲氧基化衍生物，然后使它们与2-乙醇胺和3-丙醇胺化学选择性反应，形成相应的氨基醇。 。通过肉汤微稀释法测定物质的抗菌活性和调节活性，以确定最低抑菌浓度（MIC）。使用ChEMBL数据库分析了分子结构，以预测可能的药理目标，该目标指出分子2-（2-羟基-乙胺）-3-（2-甲基丙烯基）-[1,4]萘醌为可能的抗菌剂蛋白质复制剂解旋酶和RecA。该化合物具有低分子量和少量可旋转键。该物质的MICs
• Inhibition of Staphylococcus aureus TetK and MsrA efflux pumps by hydroxyamines derived from lapachol and norlachol
  作者：Fernando Gomes Figueredo、Rodrigo Emmanuel L. T. Parente、Maynara Rodrigues Cavalcante-Figueredo、Jakson Gomes Figueiredo、Raimundo Luiz Pereira da Silva、Edinardo Fagner Ferreira Matias、Tania Maria Sarmento Silva、Celso Amorim Camara、Cícera Datiane de Morais Oliveira-Tintino、Saulo Relison Tintino、Henrique Douglas Melo Coutinho、Marta Maria de Franca Fonteles

  DOI：10.1007/s10863-021-09885-5

  日期：2021.4

  The present study aimed to evaluate the in vitro efflux pump inhibitory capacity of hydroxyamines derived from lapachol and norlachol, where compounds 3, 4, and 5 were tested against the S. aureus strains: RN4220 carrying the pUL5054 plasmid; and IS-58, endowed with the PT181 plasmid. The substances were synthesized from 2-hydroxy-quinones, lapachol and nor-lapachol obtaining the corresponding 2-methoxylated derivatives via dimethyl sulfate alkylation in a basic medium, which then reacted chemoselectively with 2-ethanolamine and 3-propanolamine to form the corresponding amino alcohols. The antibacterial action of the substances was quantified by determining the Minimum Inhibitory Concentration (MIC), while a microdilution assay was carried out to ascertain efflux pump inhibition of Staphylococcus aureus strains carrying the MsrA macrolide and the TetK tetracycline efflux pumps with the substances at a sub-inhibitory concentration. The results were subjected to statistical analysis by an ANOVA test and Bonferroni post hoc test. The MIC from the substances exhibited a value ≥ 1024 µg/mL. However, a significant reduction (p < 0.0001) of the erythromycin, tetracycline and ethidium bromide MIC was demonstrated when these were in combination with the substances, with this effect being due to a supposed efflux pump inhibition. The tested substances demonstrated effectiveness at decreasing the MIC of erythromycin, tetracycline and ethidium bromide, potentially by inhibiting the MsrA macrolide and the TetK tetracycline efflux pumps present in the tested S. aureus strains.

  本研究旨在评估拉帕酚和去甲拉酚衍生的羟胺的体外外排泵抑制能力，其中化合物 3、4 和 5 针对金黄色葡萄球菌菌株进行了测试：携带 pUL5054 质粒的 RN4220；携带 pUL5054 质粒的 RN4220；和IS-58，赋予PT181质粒。该物质由2-羟基醌、拉帕酚和正拉帕酚在碱性介质中通过硫酸二甲酯烷基化得到相应的2-甲氧基化衍生物，然后与2-乙醇胺和3-丙醇胺发生化学选择性反应生成相应的氨基醇。通过测定最低抑菌浓度 (MIC) 来量化这些物质的抗菌作用，同时进行微量稀释测定，以确定这些物质在亚浓度下对携带 MsrA 大环内酯和 TetK 四环素外排泵的金黄色葡萄球菌菌株的外排泵抑制作用。 -抑制浓度。结果通过 ANOVA 检验和 Bonferroni 事后检验进行统计分析。这些物质的 MIC 值≥≥1024 µg/mL。然而，当红霉素、四环素和溴化乙锭与这些物质合用时，其 MIC 显着降低 (p<0.0001)，这种效应是由于假定的外排泵抑制所致。测试物质显示出可有效降低红霉素、四环素和溴化乙锭的 MIC，这可能是通过抑制测试金黄色葡萄球菌菌株中存在的 MsrA 大环内酯和 TetK 四环素外排泵来实现的。
• Beyond Topoisomerase Inhibition: Antitumor 1,4-Naphthoquinones as Potential Inhibitors of Human Monoamine Oxidase
  作者：Eduardo Coelho-Cerqueira、Paulo A. Netz、Vanessa P. do Canto、Angelo C. Pinto、Cristian Follmer

  DOI：10.1111/cbdd.12255

  日期：2014.4

  Monoamine oxidase (MAO) action has been involved in the regulation of neurotransmitters levels, cell signaling, cellular growth, and differentiation as well as in the balance of the intracellular polyamine levels. Although so far obscure, MAO inhibitors are believed to have some effect on tumors progression. 1,4‐naphthoquinone (1,4‐NQ) has been pointed out as a potential pharmacophore for inhibition of both MAO and DNA topoisomerase activities, this latter associated with antitumor activity. Herein, we demonstrated that certain antitumor 1,4‐NQs, including spermidine‐1,4‐NQ, lapachol, and nor‐lapachol display inhibitory activity on human MAO‐A and MAO‐B. Kinetic studies indicated that these compounds are reversible and competitive MAO inhibitors, being the enzyme selectivity greatly affected by substitutions on 1,4‐NQ ring. Molecular docking studies suggested that the most potent MAO inhibitors are capable to bind to the MAO active site in close proximity of flavin moiety. Furthermore, ability to inhibit both MAO‐A and MAO‐B can be potentialized by the formation of hydrogen bonds between these compounds and FAD and/or the residues in the active site. Although spermidine‐1,4‐NQs exhibit antitumor action primarily by inhibiting topoisomerase via DNA intercalation, our findings suggest that their effect on MAO activity should be taken into account when their application in cancer therapy is considered.