Ethyl 3-(2-ethoxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate | 1513847-96-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Ethyl 3-(2-ethoxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate
• 英文别名: ethyl 3-(2-ethoxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate
• CAS: 1513847-96-5
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: ZFVXZRXWLZAHST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  57.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 3-(2-ethoxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate 在 盐酸羟胺 作用下， 反应 24.0h， 生成 3-(2-ethoxyphenyl)-N-hydroxy-4,5-dihydroisoxazole-5-carboxamide
  参考文献：
  名称：

  Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease

  摘要：

  This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases

  DOI：

  10.3109/14756366.2015.1077330
• 作为产物：
  描述：

  2-乙氧基苯甲醛 在 三氯异氰尿酸 、 盐酸羟胺 、 三乙胺 作用下， 反应 26.5h， 生成 Ethyl 3-(2-ethoxyphenyl)-4,5-dihydro-1,2-oxazole-5-carboxylate
  参考文献：
  名称：

  Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease

  摘要：

  This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases

  DOI：

  10.3109/14756366.2015.1077330

文献信息

• [2 + 2 + 1] Cycloaddition of <i>N</i>-tosylhydrazones, <i>tert</i>-butyl nitrite and alkenes: a general and practical access to isoxazolines
  作者：Liang Ma、Feng Jin、Xionglve Cheng、Suyan Tao、Gangzhong Jiang、Xingxing Li、Jinwei Yang、Xiaoguang Bao、Xiaobing Wan

  DOI：10.1039/d1sc02352g

  日期：——

  N-tosylhydrazones has not been examined. Herein, we report the first demonstrations of [2 + 2 + 1] cycloaddition reactions that allow the facile synthesis of isoxazolines, employing N-tosylhydrazones, tert-butyl nitrite (TBN) and alkenes as reactants. This process represents a new type of cycloaddition reaction with a distinct mechanism that does not involve the participation of nitrile oxides. This

  在过去的几十年里， N-甲苯磺酰腙已被证明是多功能的合成子。然而，据我们所知，基于N-甲苯磺酰腙的异恶唑啉的构建尚未得到研究。在此，我们报告了[2 + 2 + 1]环加成反应的首次演示，该反应可以使用N-甲苯磺酰腙、亚硝酸叔丁酯（TBN）和烯烃作为反应物轻松合成异恶唑啉。该过程代表了一种新型的环加成反应，具有独特的机制，不涉及氧化腈的参与。这种方法既通用又实用，具有广泛的底物范围、几乎通用的官能团兼容性、对水分和空气的耐受性、复杂生物活性分子功能化的潜力，并且易于扩大规模。对照实验和理论计算都表明，这种转化是通过N-甲苯磺酰腙和 TBN 的偶联原位生成硝基化合物，然后与烯烃进行环加成，然后消除叔丁氧基，得到所需的异恶唑啉。
• Design, Synthesis, and Evaluation of Hydroxamic Acid Derivatives as Promising Agents for the Management of Chagas Disease
  作者：Giseli Capaci Rodrigues、Daniel Ferreira Feijó、Marcelo Torres Bozza、Peiwen Pan、Daniela Vullo、Seppo Parkkila、Claudiu T. Supuran、Clemente Capasso、Alcino Palermo Aguiar、Alane Beatriz Vermelho

  DOI：10.1021/jm400902y

  日期：2014.1.23

  Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5 ''. -dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g)was evaluated in detail and shows promising features as an antitrypanosomal agent. Excellent values for the inhibition of growth for all three developmental forms of the parasite were observed at low concentrations of 5g (IC50 values from 7.0 to <1 mu M). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream parasites and that all treated mice survived; it was also more effective than the standard drug benznidazole.
• Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease
  作者：Dayanne da Rocha de Menezes、Claudia Magalhães Calvet、Giseli Capaci Rodrigues、Mirian Claudia de Souza Pereira、Igor Rodrigues Almeida、Alcino Palermo de Aguiar、Claudiu T. Supuran、Alane Beatriz Vermelho

  DOI：10.3109/14756366.2015.1077330

  日期：2016.11.1

  This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases