4-乙酰氨基-3-硝基苯甲酸甲酯 | 6313-39-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-乙酰氨基-3-硝基苯甲酸甲酯
• 英文名称: methyl 4-acetamido-3-nitrobenzoate
• 英文别名: Methyl 4-(acetylamino)-3-nitrobenzoate
• CAS: 6313-39-9
• 化学式: C₁₀H₁₀N₂O₅
• 分子量: 238.2
• InChiKey: LOLJRBYFAVSFOA-UHFFFAOYSA-N

物化性质

• 沸点：
  457.1±35.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-乙酰氨基-3-硝基苯甲酸甲酯 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 氢气 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 2.5h， 生成 (3,4-二氨基苯基)甲醇
  参考文献：
  名称：

  Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors

  摘要：

  Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

  DOI：

  10.1021/jm00025a008
• 作为产物：
  描述：

  对乙酰氨基苯甲酸 在 sodium hydroxide 、 硝酸 作用下， 以 氯仿 、 水 为溶剂， 反应 22.0h， 生成 4-乙酰氨基-3-硝基苯甲酸甲酯
  参考文献：
  名称：

  Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors

  摘要：

  Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

  DOI：

  10.1021/jm00025a008

文献信息

• Structure-Based Inhibitors of Influenza Virus Sialidase. A Benzoic Acid Lead with Novel Interaction
  作者：Sangeeta Singh、Marek J. Jedrzejas、Gillian M. Air、Ming Luo、W. Graeme Laver、Wayne J. Brouillette

  DOI：10.1021/jm00017a005

  日期：1995.8

  for infection of the virus. The catalytic site is highly conserved among all known influenza variants, suggesting that this protein is a suitable target for drug intervention. The most potent known inhibitors are analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), particularly the 4-guanidino derivative (4-guanidino-Neu5Ac2en). We utilized the benzene ring of 4-(N-acetylamino)benzoic

  流感病毒唾液酸酶是一种表面酶，对于感染病毒至关重要。在所有已知的流感变体中，催化位点均高度保守，表明该蛋白是药物干预的合适靶标。最有效的已知抑制剂是2-脱氧-2，3-二氢-N-乙酰神经氨酸（Neu5Ac2en），特别是4-胍基衍生物（4-胍基-Neu5Ac2en）的类似物。我们利用4-（N-乙酰氨基）苯甲酸的苯环作为环状模板替代Neu5Ac2en的二氢吡喃环。在这项研究中，准备了几种3-（N-酰基氨基）衍生物作为Neu5Ac2en甘油侧链的潜在替代物，并且发现其中一些与唾液酸酶的相同结合亚位相互作用。更重要的意义是观察到，迄今为止确定的最有效的流感唾液酸酶苯甲酸抑制剂（IC50 = 10 microM）3-胍基苯甲酸衍生物（相当于4-胍基-Neu5Ac2en的4-胍基）。与胍基结合子位点相反，唾液酸酶上的甘油结合子位点。因此，该苯甲酸衍生物提供了一种新化合物，该化合物以新颖的方式与流感唾液酸酶的催化​​位点相互作用。
• Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors
  作者：Pattaporn Jaikhan、Benjaporn Buranrat、Yukihiro Itoh、Jiranan Chotitumnavee、Takashi Kurohara、Takayoshi Suzuki

  DOI：10.1016/j.bmcl.2019.03.028

  日期：2019.5

  attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone

  Fe（II）/α-酮戊二酸依赖性赖氨酸脱甲基酶（KDMs）是多种疾病（包括癌症）的引人注目的药物靶标。在这项研究中，我们设计和筛选了有望用作Fe（II）螯合剂的邻位取代的酸酐，并确定了邻羟基苯胺作为KDM5A抑制剂的新型支架。用4-羧基-2-羟基甲酰苯胺（9c）的前药形式治疗人肺癌A549细胞时，组蛋白H3水平上的三甲基赖氨酸4含量增加，提示该细胞中存在KDM5抑制作用。
• Regioselective nitration of anilines with Fe(NO₃)₃·9H₂O as a promoter and a nitro source
  作者：Yang Gao、Yuanyou Mao、Biwei Zhang、Yingying Zhan、Yanping Huo

  DOI：10.1039/c8ob00841h

  日期：——

  An efficient Fe(NO3)3·9H2O promoted ortho-nitration reaction of aniline derivatives has been developed. This reaction may go through a nitrogen dioxide radical (NO2˙) intermediate, which is generated by the thermal decomposition of iron(III) nitrate. The practicality of the present method using nontoxic and inexpensive iron reagents has been shown by the broad substrate scope and applications.

  已经开发出一种有效的Fe（NO 3）3 ·9H 2 O促进苯胺衍生物的邻位硝化反应。该反应可能通过二氧化氮自由基（NO 2）中间体，该中间体是由硝酸铁（III）的热分解产生的。广泛的底物范围和应用已经证明了使用无毒且廉价的铁试剂的本方法的实用性。
• 1-Aryl-3-(4-methoxybenzyl)ureas as potentially irreversible glycogen synthase kinase 3 inhibitors: Synthesis and biological evaluation
  作者：Jana Venter、Concepción Perez、Willem A.L. van Otterlo、Ana Martínez、Margaret A.L. Blackie

  DOI：10.1016/j.bmcl.2019.04.049

  日期：2019.7

  Glycogen synthase kinase 3 (GSK-3) has become known for its multifactorial involvement in the pathogenesis of Alzheimer's disease. In this study, a benzothiazole- and benzimidazole set of 1-aryl-3-(4-methoxybenzyl)ureas were synthesised as proposed Cys199-targeted covalent inhibitors of GSK-3β, through the incorporation of an electrophilic warhead onto their ring scaffolds. The nitrile-substituted

  糖原合酶激酶3（GSK-3）因其多因素参与阿尔茨海默氏病的发病机理而闻名。在这项研究中，通过将亲电子战斗部结合到环支架上，合成了拟议的Cys199靶向GSK-3β共价抑制剂，合成了1-芳基-3-（4-甲氧基苄基）脲的苯并噻唑和苯并咪唑组。与参考抑制剂AR-A014418（1，IC50 = 0.072）相比，腈取代的苯并咪唑基尿素2b（IC50 = 0.086±0.023 µM）和卤代甲基酮取代的苯并咪唑基尿素9b（IC50 = 0.13±0.060 µM）具有较高的GSK-3β抑制活性。 ±0.043）。结果表明，对2b和9b作为GSK-3β的潜在共价抑制剂的进一步研究，因为靶向相互作用可能提供改善的激酶选择性。
• Inhibitors of influenza virus neuraminidase and methods of making and
  申请人：The University of Alabama at Birmingham

  公开号：US05453533A1

  公开（公告）日：1995-09-26

  An influenza virus neuraminidase inhibitor, its analogs, its pharmaceutically acceptable salts, derivatives, and mixtures thereof having the following formula: ##STR1## where A is CO.sub.2 H, CO.sub.2 H.sub.3, NO.sub.2, SO.sub.3 H or PO.sub.3 H.sub.2, B is CH, N, O or S, R.sub.1 and R.sub.2 are H, NO.sub.2 or (CH.sub.m).sub.n X.sub.1 where m=1 or 2, n is an integer from 0 to 4 and X.sub.1 is guanidino, OH, NH.sub.2, SH, NO.sub.2, F, Cl, Br, I, CN, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2, R.sub.3 and R.sub.4 are H, (CH.sub.o).sub.p X.sub.2, (CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2, NH(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2, NHCO(CH.sub.o).sub.p CH.sub.2 X.sub.2 or NHCO(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2 where o=1 or 2, p is an integer from 0 to 4 and X.sub.2 is H, guanidino, OH, NH.sub.2, SH, NO.sub.2, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2 , R.sub.5 =H, OH, NH.sub.2, (CH.sub.k).sub.1 X.sub.3, CO(CH.sub.k).sub.1 X.sub.3, SO(CH.sub.k).sub.1 X.sub.3 or SO.sub.2 (CH.sub.k).sub.1 X.sub.3 where k=1 or 2, 1 is an integer from 0 to 4 and X.sub.3 is guanidino, OH, NH.sub.2, SH, NO.sub.2, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2, R.sub.6 is H, CH(OH)X.sub.4, CH(NH.sub.2)X.sub.4, COX.sub.4, SOX.sub.4, or SO.sub.2 X.sub.4, where X.sub.4 is H, CH.sub.3, CH.sub.3 CH.sub.2, CH.sub.3 CHCH.sub.3, CH.sub.3 CH.sub.2 CH.sub.2 or halogen substituted analogs of X.sub.4. The inhibitor in a composition with a pharmaceutically acceptable carrier. A method of inhibiting influenza virus neuraminidase where the inhibitor is administered to a subject in a pharmaceutically acceptable amount along with effective amounts of a pharmaceutically acceptable carrier. Methods of marking a pharmaceutical composition of an acceptable carrier and the inhibitor. Methods of treating and preventing a subject infected with influenza virus (type A or B) using the inhibitor.

  一种流感病毒神经氨酸酶抑制剂，其类似物，其药用可接受的盐，衍生物和混合物具有以下结构式：##STR1##其中A为CO.sub.2 H，CO.sub.2 H.sub.3，NO.sub.2，SO.sub.3 H或PO.sub.3 H.sub.2，B为CH，N，O或S，R.sub.1和R.sub.2为H，NO.sub.2或(CH.sub.m).sub.n X.sub.1，其中m=1或2，n是0到4的整数，X.sub.1为胍基，OH，NH.sub.2，SH，NO.sub.2，F，Cl，Br，I，CN，CF.sub.3，CO.sub.2 H，SO.sub.3 H或PO.sub.3 H.sub.2，R.sub.3和R.sub.4为H，(CH.sub.o).sub.p X.sub.2，(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2，NH(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2，NHCO(CH.sub.o).sub.p CH.sub.2 X.sub.2或NHCO(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2，其中o=1或2，p是0到4的整数，X.sub.2为H，胍基，OH，NH.sub.2，SH，NO.sub.2，CF.sub.3，CO.sub.2 H，SO.sub.3 H或PO.sub.3 H.sub.2，R.sub.5=H，OH，NH.sub.2，(CH.sub.k).sub.1 X.sub.3，CO(CH.sub.k).sub.1 X.sub.3，SO(CH.sub.k).sub.1 X.sub.3或SO.sub.2(CH.sub.k).sub.1 X.sub.3，其中k=1或2，l是0到4的整数，X.sub.3为胍基，OH，NH.sub.2，SH，NO.sub.2，CF.sub.3，CO.sub.2 H，SO.sub.3 H或PO.sub.3 H.sub.2，R.sub.6为H，CH(OH)X.sub.4，CH(NH.sub.2)X.sub.4，COX.sub.4，SOX.sub.4或SO.sub.2 X.sub.4，其中X.sub.4为H，CH.sub.3，CH.sub.3 CH.sub.2，CH.sub.3 CHCH.sub.3，CH.sub.3 CH.sub.2 CH.sub.2或X.sub.4的卤素取代物。抑制剂与药用可接受的载体组成的组合物。一种抑制流感病毒神经氨酸酶的方法，其中将抑制剂与药用可接受的载体一起以药用可接受的剂量给予受试者。标记含有可接受载体和抑制剂的药物组合物的方法。使用该抑制剂治疗和预防感染流感病毒（A型或B型）的受试者的方法。