1-fluoro-5-methoxy-2,4-dinitrobenzene | 394-18-3

• 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-fluoro-5-methoxy-2,4-dinitrobenzene
• 英文别名: 2,4-Dinitro-5-fluoroanisole
• CAS: 394-18-3
• 化学式: C₇H₅FN₂O₅
• 分子量: 216.126
• InChiKey: BKYHMDNLFGUECN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-fluoro-5-methoxy-2,4-dinitrobenzene 在 sodium dithionite 、 氨 作用下， 以 水 为溶剂， 反应 3.0h， 以85%的产率得到4-氟-2-甲氧基-5-硝基苯胺
  参考文献：
  名称：

  一种奥希替尼中间体的合成方法

  摘要：

  本发明涉及一种奥希替尼中间体的合成方法，包括以下步骤：1、取3‑氟苯甲醚作为起始原料，添加到浓硫酸中，在低温环境下滴加浓硝酸，滴加完毕后，进行第一次升温搅拌，后将体系注入冰水中淬灭，然后进行第二次升温搅拌，过滤得产品3‑氟‑4，6‑二硝基苯甲醚；2、将第一步所得化合物3‑氟‑4，6‑二硝基苯甲醚加入到水中，再加入碱，升温，分批加入弱还原剂，保温搅拌至反应终点，过滤后得到粗品，再依次进行洗涤、用甲醇重结晶、低温析晶过滤、烘干，最终得到4‑氟‑2‑甲氧基‑5‑硝基苯胺。本发明解决了现有技术中奥希替尼中间体的合成方法存在原材料价格昂贵且市场不易得、工艺复杂和收率低的问题。

  公开号：

  CN112341346A
• 作为产物：
  描述：

  间氟苯甲醚 在 indium(III) triflate 、 5-methyl-1,3 dinitropyrazole 作用下， 反应 16.0h， 以65%的产率得到1-fluoro-5-methoxy-2,4-dinitrobenzene
  参考文献：
  名称：

  从N-H硝化到可控芳烃单硝化和二硝化——多功能高效N-硝基吡唑硝化试剂的发现

  摘要：

  硝基芳烃是非常有价值的有机化合物，长期以来被用作药物、农用化学品和炸药以及多种化学品的重要中间体。因此，芳香硝化的探索已成为学术界和工业界的一项重要工作。在此，我们报告了从N使用实用的 N-H 硝化方法构建的硝基型试剂库。这种硝化试剂可作为硝鎓离子的可控来源，能够对具有良好官能团耐受性的多种（杂）芳烃进行温和且可扩展的硝化。值得注意的是，我们的硝化方法可以通过操纵反应条件来控制，以选择性地提供单硝化或二硝化产物。这种方法在药物化学中的价值已经通过其对复杂生物相关分子的高效后期 C-H 硝化而得到了很好的证实。密度泛函理论 (DFT) 计算和初步机理研究表明，这种硝化试剂的强大功能和多功能性是由于协同的“硝基效应”和“甲基效应”。

  DOI：

  10.1021/jacsau.2c00413

文献信息

• Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors
  作者：Lianbao Ye、Tao Zhao、Wenjun Du、Anhu Li、Wei Gao、Jingrong Li、Ling Wang、Weiqiang Chen

  DOI：10.1080/14756366.2019.1634704

  日期：2019.1.1

  and was proven to be effective against multiple EGFR mutations. In previous study, we reported spiro [indoline-3, 4′-piperidine]-2-ones as anticancer agents. In this study, we designed aminopyridine-containing spiro [indoline-3,4′-piperidine] derivatives A1-A4 using Neratinib and spiro [indoline-3, 4′-piperidine]-2-one compound patented as lead structure, then replaced piperidine with cyclopropane to

  抽象的 Neratinib是口服pan HER抑制剂，不可逆地抑制EGFR和HER2，并被证明对多种EGFR突变有效。在以前的研究中，我们报道了螺[吲哚啉-3，4'-哌啶] -2-酮作为抗癌药。在这项研究中，我们使用Neratinib和螺环[indoline-3,4'-哌啶] -2-one专利作为前导结构的化合物，设计了含氨基吡啶的螺[indoline-3,4'-哌啶] -2衍生物A1-A4，然后将其取代用环丙烷用哌啶制得B1-B7，用苯并吗啉代替二氢吲哚制得C1-C4和D1-D2。我们合成了这些化合物，并评估了在0.5 M药物浓度下对EGFR和ERBB2的残留活性。大多数化合物对EGFR-wt和ERBB2表现出较强的抑制作用，其中A1-A4表现出优异的抑制活性，对EGFR-wt激酶的抑制率分别为7％，6％，19％，27％和9％，5％ ，分别为ERBB2激酶的12％，34％，而那拉替尼的2％和6％。
• Enantioselective Nucleophilic Aromatic Substitution Reaction of Azlactones to Synthesize Quaternary α-Amino Acid Derivatives
  作者：Xiaohua Liu、Yi Li、Hao Pan、Wang-Yuren Li、Xiaoming Feng

  DOI：10.1055/a-1323-2389

  日期：2021.4

  An asymmetric organocatalytic nucleophilic aromatic substitution reaction of azlactones with electron-deficient aryls was established. A variety of α-aryl α-alkyl α-amino acid esters and peptides were obtained in decent yields and stereoselectivities. A new bifunctional catalytic mode involving charge-transfer interaction and hydrogen bonding is proposed to explain the enantioselectivity.

  建立了a内酯与缺电子芳基的不对称有机催化亲核芳香取代反应。以适当的产率和立体选择性获得了多种α-芳基α-烷基α-氨基酸酯和肽。提出了一种新的涉及电荷转移相互作用和氢键的双功能催化模式来解释对映选择性。
• Diazeniumdiolated compounds, pharmaceutical compositions, and method of treating cancer
  申请人：Maciag Anna E.

  公开号：US09205091B2

  公开（公告）日：2015-12-08

  Disclosed is a method of treating cancer in a patient comprising administering to the patient an effective amount of a diazeniumdiolated (N2O2-containing) compound or a pharmaceutically acceptable salt thereof, wherein the cancer cell has an elevated level of reactive oxygen species (ROS) and/or a decreased level of one or more of PRX1, PRX6, and OGG1, compared to a normal cell of the same tissue or tissue type. An example of a diazeniumdiolated compound is Formula (I), wherein X and Q are defined herein. Also disclosed are diazeniumdiolated compounds, pharmaceutical compositions, and methods of use including enhancing the chemotherapeutic treatment of chemotherapeutic agents and high energy radiation.

  本发明公开了一种治疗癌症的方法，包括向患者施用有效量的重氮二氧化物化合物或其药用盐，其中癌细胞的反应性氧化物种（ROS）水平升高和/或与同一组织或组织类型的正常细胞相比，PRX1、PRX6和OGG1中的一个或多个水平降低。重氮二氧化物化合物的一个例子是式（I），其中X和Q在此定义。本发明还公开了重氮二氧化物化合物、药物组成物和使用方法，包括增强化疗药物和高能辐射的化疗治疗。
• Benzimidazole-based compounds kill Mycobacterium tuberculosis
  作者：Yaling Gong、Selin Somersan Karakaya、Xiaoyong Guo、Purong Zheng、Ben Gold、Yao Ma、David Little、Julia Roberts、Thulasi Warrier、Xiuju Jiang、Maneesh Pingle、Carl F. Nathan、Gang Liu

  DOI：10.1016/j.ejmech.2014.01.039

  日期：2014.3

  Tuberculosis remains one of the deadliest infectious diseases, killing 1.4 million people annually and showing a rapid increase in cases resistant to multiple drugs. New antibiotics against tuberculosis are urgently needed. Here we describe the design, synthesis and structure activity relationships of a series of benzimidazole-based compounds with activity against Mycobacterium tuberculosis (Mtb) in a replicating state, a physiologically-induced non-replicating state, or both. Compounds 49, 67, 68, 69, 70, and 72, which shared a 5-nitrofuranyl moiety, exhibited high potency and acceptable selectivity indices (SI). As illustrated by compound 70 (MIC90 < 0.049 mu g/mL, SI > 512), the 5-nitrofuranyl group was compatible with minimal cytotoxicity and good intra-macrophage killing, although it lacked non-replicating activity when assessed by CFU assays. Compound 70 had low mutagenic potential by SOS Chromotest assay, making this class of compounds good candidates for further evaluation and target identification. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Activation of the c-Jun N-terminal Kinase/Activating Transcription Factor 3 (ATF3) Pathway Characterizes Effective Arylated Diazeniumdiolate-Based Nitric Oxide-Releasing Anticancer Prodrugs
  作者：Anna E. Maciag、Rahul S. Nandurdikar、Sam Y. Hong、Harinath Chakrapani、Bhalchandra Diwan、Nicole L. Morris、Paul J. Shami、Yih-Horng Shiao、Lucy M. Anderson、Larry K. Keefer、Joseph E. Saavedra

  DOI：10.1021/jm2004128

  日期：2011.11.24

  Improved therapies are needed for nonsmall cell lung cancer. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Recently, we have shown that O-2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, 1) is effective against nonsmall cell lung cancer (NSCLC) cells in culture and in vivo. Here we report mechanistic studies with compound 1 and its homopiperazine analogue and structural modification of these into more stable prodrugs. Compound 1 and its., homopiperazine analogue were potent cytotoxic agents against NSCLC cells in vitro and in vivo, concomitant with activation of the SAPK/JNK stress pathway and upregulation of its downstream effector ATF3. Apoptosis followed these events. An aryl-substituted analogue, despite extended half-life in the presence of glutathione, did not activate JNK or have antitumor activity. The data suggest that rate of reactivity with glutathione and activation of JNK/ATF3 are determinants of cancer cell killing by these prodrugs.