2-hydroxy-5-nitrophenylacetic acid methyl ester | 155388-58-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-hydroxy-5-nitrophenylacetic acid methyl ester
• 英文别名: Methyl 2-(2-hydroxy-5-nitrophenyl)acetate
• CAS: 155388-58-2
• 化学式: C₉H₉NO₅
• 分子量: 211.174
• InChiKey: XJASWUDUGKTJKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-hydroxy-5-nitrophenylacetic acid methyl ester 在 氢氧化钾 、 水 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 邻二氯苯 为溶剂， 反应 22.0h， 生成 methyl 2-(methylthio)-5-nitrophenylacetate
  参考文献：
  名称：

  Leaving group effects in reductively triggered fragmentation of 4-nitrobenzyl carbamates †

  摘要：

  报告了通过放射性、酶和化学方法将硝基还原后，一系列取代苯胺从 4-硝基苄基氨基甲酸酯中释放出来的速率和程度。释放出的苯胺的产率在 pH 值为 4-7 的范围内下降，但与离开苯胺的碱性无关。对一个例子的碎裂过程进行的详细研究发现，4-羟胺是关键的中间体。当 pH 值大于 5 时，释放出的苯胺 3b 与反应性 4- 亚氨基喹啉甲烷中间体 4a 缩合，生成胺 26，从而消耗了可测量的苯胺 3b 释放量。当 pH 值小于 5 时，胺的释放会进行到底。还原触发释放苯胺 7 的效率随离去基团的微小变化而变化，但这与苯胺的碱性并不一致。释放出的苯胺 3b 发生竞争反应生成胺 26，从而降低了 3b 的释放效率。这种反应发生在研究中使用的相对较高的浓度（50 μM）下，表明释放的效应胺在浓度大大低于 50 μM 时就会产生毒性。这凸显了在肿瘤定向硝基还原酶酶促药物疗法中使用强效细胞毒性效应物质原药的必要性。

  DOI：

  10.1039/b000135j
• 作为产物：
  描述：

  邻羟基苯乙酸 在 硫酸 、 硝酸 作用下， 反应 16.0h， 生成 2-hydroxy-5-nitrophenylacetic acid methyl ester
  参考文献：
  名称：

  Leaving group effects in reductively triggered fragmentation of 4-nitrobenzyl carbamates †

  摘要：

  报告了通过放射性、酶和化学方法将硝基还原后，一系列取代苯胺从 4-硝基苄基氨基甲酸酯中释放出来的速率和程度。释放出的苯胺的产率在 pH 值为 4-7 的范围内下降，但与离开苯胺的碱性无关。对一个例子的碎裂过程进行的详细研究发现，4-羟胺是关键的中间体。当 pH 值大于 5 时，释放出的苯胺 3b 与反应性 4- 亚氨基喹啉甲烷中间体 4a 缩合，生成胺 26，从而消耗了可测量的苯胺 3b 释放量。当 pH 值小于 5 时，胺的释放会进行到底。还原触发释放苯胺 7 的效率随离去基团的微小变化而变化，但这与苯胺的碱性并不一致。释放出的苯胺 3b 发生竞争反应生成胺 26，从而降低了 3b 的释放效率。这种反应发生在研究中使用的相对较高的浓度（50 μM）下，表明释放的效应胺在浓度大大低于 50 μM 时就会产生毒性。这凸显了在肿瘤定向硝基还原酶酶促药物疗法中使用强效细胞毒性效应物质原药的必要性。

  DOI：

  10.1039/b000135j

文献信息

• Npy antagonists, preparation and uses
  申请人：Botez Iuliana

  公开号：US20090233910A1

  公开（公告）日：2009-09-17

  The present invention concerns novel compounds, their preparation and their uses, therapeutic uses in particular. More specifically it concerns derivative compounds having at least two aromatic cycles, their preparation and their uses, in particular in the area of human or animal health. These compounds have an affinity for the biological receptors of neuropeptide Y, NPY, present in the central and peripheral nervous systems. The compounds of the invention are preferably NPY antagonists, and more particularly antagonists of sub-type NPY Y1, and can therefore be used for the therapeutic or prophylactic treatment of any disorder involving NPY. The present invention also concerns pharmaceutical compositions containing said compounds, their preparation and their uses, as well as treatment methods using said compounds.

  本发明涉及新颖化合物，它们的制备和用途，特别是在治疗方面的用途。更具体地说，它涉及至少具有两个芳香环的衍生化合物，它们的制备和用途，特别是在人类或动物健康领域。这些化合物对存在于中枢和外周神经系统中的神经肽Y（NPY）的生物受体具有亲和力。本发明的化合物优选为NPY拮抗剂，更具体地说是NPY Y1亚型的拮抗剂，因此可用于治疗或预防涉及NPY的任何疾病。本发明还涉及含有所述化合物的药物组合物，其制备和用途，以及使用所述化合物的治疗方法。
• Esterification-nitration of<i>Ortho</i>-hydroxyphenyl Carboxylic Acids and Benzoic Acids with Cerium(IV) Ammonium Nitrate (CAN)
  作者：Wen-Bin Pan、Li-Mei Wei、Li-Lan Wei、Chin-Chung Wu、Yang-Chang Wu

  DOI：10.1002/jccs.200500027

  日期：2005.2

  without a dehydrating reagent or water removal equipment. A series of ortho-hydroxyphenyl carboxylic acids and benzoic acids were transformed to their corresponding methyl esters under CAN/CH 3 OH reaction conditions. Whereas in an aprotic solvent, acetonitrile, sp 3 -C tethered ortho-hydroxyphenyl carboxylic acids undergo simultaneous o,p-dinitration and intramolecular esterification reactions in good

  实现了方便且有用的酯化反应，并且该反应在没有脱水剂或除水设备的情况下进行。在CAN/CH 3 OH 反应条件下，一系列邻羟基苯基羧酸和苯甲酸被转化为相应的甲酯。而在非质子溶剂中，乙腈、sp 3 -C 连接的邻羟基苯基羧酸以良好的收率同时进行邻、对二硝化和分子内酯化反应。此外，2-((lE)-2-nitrovinyl)-4-nitrophenol (3e) 对 MCF-7、HEP G2 和 HEP 3B 细胞系显示出选择性细胞毒性，IC 5 0 值为 23.50、7.33 和 7.59 ug/毫升，分别。
• Structure-Activity Relationships in a Series of 5-[(2,5-Dihydroxybenzyl)amino]salicylate Inhibitors of EGF-Receptor-Associated Tyrosine Kinase: Importance of Additional Hydrophobic Aromatic Interactions
  作者：Huixiong Chen、Janine Boiziau、Fabienne Parker、Patrick Mailliet、Alain Commercon、Bruno Tocque、Jean-Bernard Le Pecq、Bernard-Pierre Roques、Christiane Garbay

  DOI：10.1021/jm00032a020

  日期：1994.3

  Potent inhibitors of EGF-dependent protein tyrosine kinase (PTK) activity were synthesized in a series of 5-[(2,5-dihydroxybenzyl)amino]salicylates. Several of these compounds inhibited EGF-dependent DNA synthesis in ER 22 cells with IC50 < 1 muM. In this series of PTK inhibitors, the role of the salicylate moiety as a potential divalent ion chelator was tested and found to be nonessential in all cases. The length and ramification of the substituting carboxyl group were investigated to improve cellular bioavailability, and this analysis provided compounds with increased inhibitory effect on EGF-induced DNA synthesis. Salicylates esterified with long hydrophobic chains were shown to be noncompetitive inhibitors of ATP, in contrast to the free acid and methyl salicylate. Moreover, all the tested inhibitors were shown to be noncompetitive inhibitors of the peptide substrate. Structure-activity relationships allowed us to suspect a hydrophobic pocket in the tyrosine kinase domain, preferentially interacting with aromatic rings. Finally, the selectivity of the best inhibitors was tested against other kinases, and they were found to be selective for tyrosine kinase. They were also shown to be good inhibitors of EGF-receptor autophosphorylation.
• Leaving group effects in reductively triggered fragmentation of 4-nitrobenzyl carbamates †
  作者：Bridget M. Sykes、Michael P. Hay、Dubravka Bohinc-Herceg、Nuala A. Helsby、Charmian J. O’Connor、William A. Denny

  DOI：10.1039/b000135j

  日期：——

  The rates and extent of release of a series of substituted anilines from 4-nitrobenzyl carbamates, following nitro group reduction by radiolytic, enzymic and chemical methods, are reported. The yield of released anilines decreased over the pH range 4–7, but was independent of the basicity of the leaving aniline. Detailed studies of the fragmentation of one example identified the 4-hydroxylamine as the key intermediate. At pH greater than 5 the released aniline 3b condenses with a reactive 4-iminoquinomethane intermediate 4a to give amine 26, thus depleting the measurable amount of aniline 3b released. At pH less than 5 the release of amine proceeds to completion. The efficiency of reductively triggered release of anilines 7 varied with small changes in the leaving group, but this was not uniformly related to aniline basicity. The competing reaction of the released aniline 3b to form amine 26 lowers the efficiency of release of 3b. This reaction occurs at the relatively high concentrations (50 μM) used in the study and indicates the released effector amine should be toxic at concentrations considerably lower than 50 μM. This highlights the need for prodrugs of very potent cytotoxic effectors to be used in tumour-directed nitroreductase enzyme-prodrug therapy.

  报告了通过放射性、酶和化学方法将硝基还原后，一系列取代苯胺从 4-硝基苄基氨基甲酸酯中释放出来的速率和程度。释放出的苯胺的产率在 pH 值为 4-7 的范围内下降，但与离开苯胺的碱性无关。对一个例子的碎裂过程进行的详细研究发现，4-羟胺是关键的中间体。当 pH 值大于 5 时，释放出的苯胺 3b 与反应性 4- 亚氨基喹啉甲烷中间体 4a 缩合，生成胺 26，从而消耗了可测量的苯胺 3b 释放量。当 pH 值小于 5 时，胺的释放会进行到底。还原触发释放苯胺 7 的效率随离去基团的微小变化而变化，但这与苯胺的碱性并不一致。释放出的苯胺 3b 发生竞争反应生成胺 26，从而降低了 3b 的释放效率。这种反应发生在研究中使用的相对较高的浓度（50 μM）下，表明释放的效应胺在浓度大大低于 50 μM 时就会产生毒性。这凸显了在肿瘤定向硝基还原酶酶促药物疗法中使用强效细胞毒性效应物质原药的必要性。