1-(4-羟基-3-甲氧基-5-硝基苯基)乙酮 | 20716-41-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(4-羟基-3-甲氧基-5-硝基苯基)乙酮
• 英文名称: 1-(4-hydroxy-3-methoxy-5-nitrophenyl)ethanone
• 英文别名: 4'-hydroxy-3'-methoxy-5'-nitroacetophenone
• CAS: 20716-41-0
• 化学式: C₉H₉NO₅
• mdl: MFCD20486609
• 分子量: 211.174
• InChiKey: PGKVPHVPNDBJTO-UHFFFAOYSA-N

物化性质

• 熔点：
  148.1–149.5°C
• 沸点：
  316.4±37.0 °C(Predicted)
• 密度：
  1.360±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  存储条件：2-8°C，并在氮气环境下保存。

反应信息

• 作为反应物：
  描述：

  1-(4-羟基-3-甲氧基-5-硝基苯基)乙酮 在 sodium dithionite 、 一水合肼 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Pharmacophore combination as a useful strategy to discover new antitubercular agents

  摘要：

  The present study is aimed at combining two well-known pharmacophores (pyrazoline and benzoxazole nucleus) to design and synthesize a series of substituted pyrazoline-based benzoxazole derivatives. In vitro antitubercular evaluation against Mycobacterium tuberculosis H37Rv, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains showed that most of the target compounds displayed potent activity (MIC similar to 1.25-25 mu g/mL) where few compounds were found to be better than isoniazid against MDR-TB (MIC = 3.25 mu g/mL) and XDR-TB (MIC = 12.5 mu g/mL). Cytotoxicity assay of these active compounds in VERO cell lines displayed good selectivity index. In order to gain insights into the plausible binding motifs, the target compounds were docked into enoyl-acyl carrier protein reductase, a molecular target of isoniazid. All the docked compounds occupied the same hydrophobic binding pocket and interacted mostly by dispersion interactions. Contribution of the three pharmacophoric fragments (pyrazoline, benzoxazole and aryl ring) toward protein-ligand binding was evaluated at semi empirical quantum mechanics level. The interaction energies suggested that most of the binding was governed by the benzoxaxole moiety followed by pyrazoline and aryl rings.

  DOI：

  10.1007/s00044-013-0645-x
• 作为产物：
  描述：

  香草乙酮 在 硝酸 、 溶剂黄146 作用下， 以55%的产率得到1-(4-羟基-3-甲氧基-5-硝基苯基)乙酮
  参考文献：
  名称：

  评价作为邻苯二酚-O-甲基转移酶和单胺氧化酶抑制剂的硝基儿茶酚查尔酮和吡唑啉衍生物。

  摘要：

  文献报道，查耳酮可抑制单胺氧化酶（MAO）酶，大多对MAO-B同工型具有特异性，而硝基儿茶酚化合物已被确立为儿茶酚-O-甲基转移酶（COMT）的抑制剂。基于此，提出了查尔酮的硝基邻苯二酚衍生物代表可同时抑制MAO-B和COMT的双靶标定向化合物。这两种酶均在多巴胺和左旋多巴的代谢中起关键作用，因此抑制剂与帕金森氏病的治疗有关。本研究扩展了双重MAO-B / COMT抑制剂的发现，方法是合成包括杂环衍生物在内的查耳酮的其他硝基邻苯二酚衍生物，并将其转化为相应的吡唑啉衍生物。评价新合成的查耳酮和吡唑啉化合物作为人MAO和大鼠COMT的抑制剂，并将抑制能力表示为IC 50值。吡唑啉衍生物化合物8b是最有效的COMT抑制剂，IC50值为0.048μM。这比参考COMT抑制剂entacapone更有效，后者的IC50值为0.23μM。结果表明，吡唑啉衍生物（IC50 = 0.048-0.21 µM）是比查耳酮（IC50

  DOI：

  10.1016/j.bmcl.2020.127188

文献信息

• 7-(3,4-二甲氧基-5-硒甲基苯基)-吡咯并[2,3-d]嘧啶及其应用
  申请人：广东省科学院动物研究所

  公开号：CN112939989A

  公开（公告）日：2021-06-11

  本发明公开了7‑(3,4‑二甲氧基‑5‑硒甲基苯基)‑吡咯并[2,3‑d]嘧啶及其应用。7‑(3,4‑二甲氧基‑5‑硒甲基苯基)‑吡咯并[2,3‑d]嘧啶化学结构如下式(a)所示，式(a)中，R1是3‑吲哚基、4‑甲基苯基、苯基、5‑(1‑甲基吲唑基)、5‑(1‑甲基吲哚基)、3‑(1‑羟甲基吲哚基)、3‑硝基‑4‑甲氧基苯基或4‑甲磺酰基苯基。本发明所述的7‑(3,4‑二甲氧基‑5‑硒甲基苯基)‑吡咯并[2,3‑d]嘧啶可以有效抑制肿瘤细胞的增殖，并且有很强的抑制微管蛋白的聚集能力，这为抑制肿瘤细胞增值提供一种新型微管蛋白抑制剂。
• Pharmacologically active compounds, methods for the preparation thereof
  申请人：Orion-yhtyma Oy

  公开号：US04963590A1

  公开（公告）日：1990-10-16

  Pharmacologically active catechol derivatives of formula I ##STR1## wherein R.sub.1 and R.sub.2 independently comprise hydrogen, alkyl, acyl, optionally substituted aroyl, lower alkylsulfonyl or alkylcabamoyl or taken together form a lower alkylidene or cycloalkylidene, X comprises an electronegative substituent such as halogen, nitro, cyano, lower alkylsulfonyl, sulfonamido, aldehyde, caboxyl or trifluoromethyl and R.sub.3 comprises hydrogen, halogen, hydroxy alkyl, amino, nitro, cyano, trifluoromethyl, lower alkylsulfonyl, sulfonamide, aldehyde, alkyl carbonyl, aralkylidene carbonyl or carboxyl or a group selected from ##STR2## wherein R.sub.4 comprises hydrogen, alkyl, cyano, carboxyl or acyl and R.sub.5 comprises hydrogen, cyano, carboxyl, alkoxycarbonyl, carboxyalkenyl, nitro, acyl, optionally substituted aroyl or heteroaroyl, hydroxyalkyl or carboxyalkyl or R.sub.4 and R.sub.5 together form a five to seven membered substituted cycloalkanone ring; --(CO).sub.n (CH.sub.2).sub.m --COR wherein n is 0-1 and m is 0-7 and R comprises hydroxy, alkyl, carboxyalkyl, optionally substituted alkene, alkoxy or optionally substituted amino; ##STR3## wherein R.sub.8 and R.sub.9 independently comprise hydrogen or one of the following optionally substituted groups; alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, or together form an optionally substituted piperidyl group; --NH--CO--R.sub.10 wherein R.sub.10 comprises a substituted alkyl group.

  公式I的药理活性儿茶酚衍生物，其中R.sub.1和R.sub.2独立地包括氢、烷基、酰基、可选择地取代的芳酰基、较低的烷基磺酰基或烷基氨基甲酰基，或者一起形成较低的烷基亚甲基或环烷基亚甲基，X包括电负取代基，如卤素、硝基、氰基、较低的烷基磺酰基、磺胺基、醛基、羧基或三氟甲基，R.sub.3包括氢、卤素、羟基烷基、氨基、硝基、氰基、三
• Synthesis and evaluation of selenium-containing indole chalcone and diarylketone derivatives as tubulin polymerization inhibition agents
  作者：Shun Zhang、Baijiao An、Jiayan Li、Jinhui Hu、Ling Huang、Xingshu Li、Albert S. C. Chan

  DOI：10.1039/c7ob01655g

  日期：——

  chalcone and diarylketone derivatives were synthesized and evaluated as tubulin polymerization inhibitors. Among them, compound 25b exhibited the most potent antiproliferative activities against six human cancer cell lines with IC50 values of 0.004–0.022 μM. A microtubule dynamics assay and an immunofluorescence assay confirmed that 25b could effectively inhibit tubulin polymerization (IC50 = 2.1 ± 0.27 μM)

  合成了十六种新的含硒的吲哚查尔酮和二芳基酮衍生物，并将其评估为微管蛋白聚合抑制剂。其中，化合物25b对六种人类癌细胞系表现出最有效的抗增殖活性，IC 50值为0.004-0.022μM。微管动力学分析和免疫荧光分析证实25b可有效抑制微管蛋白聚合（IC 50 = 2.1±0.27μM）。进一步的细胞机制研究表明25b诱导了G2 / M期阻滞，线粒体膜电位（MMP）的降低进一步证明了这一点。
• Discovery of Novel Benzimidazole and Indazole Analogues as Tubulin Polymerization Inhibitors with Potent Anticancer Activities
  作者：Yichang Ren、Yuxi Wang、Gang Li、Zherong Zhang、Lingling Ma、Binbin Cheng、Jianjun Chen

  DOI：10.1021/acs.jmedchem.0c01837

  日期：2021.4.22

  Novel indazole and benzimidazole analogues were designed and synthesized as tubulin inhibitors with potent antiproliferative activities. Among them, compound 12b exhibited the strongest inhibitory effects on the growth of cancer cells with an average IC50 value of 50 nM, slightly better than colchicine. 12b exhibited nearly equal potency against both, a paclitaxel-resistant cancer cell line (A2780/T

  设计并合成了新型吲唑和苯并咪唑类似物，作为具有有效抗增殖活性的微管蛋白抑制剂。其中，化合物12b对癌细胞的生长表现出最强的抑制作用，平均IC 50值为50 nM，略高于秋水仙碱。12b对紫杉醇抗性癌细胞系（A2780 / T，IC 50 = 9.7 nM）和相应的亲代细胞系（A2780S，IC 50 = 6.2 nM）表现出几乎相等的效力，因此在体外有效克服了对紫杉醇的抗性。12b的晶体结构通过X射线晶体学分析，将与微管蛋白复合的化合物拆分至2.45Å分辨率，并确认其直接结合至秋水仙碱位点。此外，12b在黑素瘤肿瘤模型中显示出显着的体内抗肿瘤功效，肿瘤生长抑制率分别为78.70％（15 mg / kg）和84.32％（30 mg / kg）。总的来说，这项工作表明12b是一种有前途的铅化合物，作为潜在的抗癌剂值得进一步研究。
• Synthesis and biological evaluations of novel apocynin analogues
  作者：Xiaoyu Lu、Sainan Wan、Jie Jiang、Xiaojian Jiang、Wenjing Yang、Pei Yu、Lipeng Xu、Zaijun Zhang、Gaoxiao Zhang、Luchen Shan、Yuqiang Wang

  DOI：10.1016/j.ejmech.2011.03.056

  日期：2011.7

  We have designed and synthesized a series of novel apocynin analogues, and evaluated their biological activity. Compound 10, an apocynin dimer analogue, compound 12, the lipoic acid (LA) and apocynin conjugate, were the most potent in protecting cells from lipopolysaccharide (LPS)-induced cytotoxicity, had significant activity scavenging ROS induced by LPS, and greatly decreased LPS-induced P67phox

  我们已经设计和合成了一系列新颖的载脂蛋白类似物，并评估了它们的生物学活性。化合物10，一个夹竹桃麻素二聚体类似物，化合物12，硫辛酸（LA）和夹竹桃麻素缀合物，是最有效的在保护细胞免于脂多糖（LPS）诱导的细胞毒性，已经显著活性清除ROS诱导LPS，并显着降低LPS诱导的P67 phox蛋白表达。SAR分析表明，载脂蛋白的修饰可以增加其活性。我们的结果表明，用强大的抗氧化剂（如硫辛酸）武装载脂蛋白是设计新的具有增强生物活性的载脂蛋白类似物的有效策略。