2-hydroxy-4-oxo-4-(2-methoxyphenyl)but-2-enoic acid ethyl ester | 1427216-72-5

• 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: 2-hydroxy-4-oxo-4-(2-methoxyphenyl)but-2-enoic acid ethyl ester
• 英文别名: ethyl 2-hydroxy-4-(2-methoxyphenyl)-4-oxo-2-butenoate
• CAS: 1427216-72-5
• 化学式: C₁₃H₁₄O₅
• 分子量: 250.251
• InChiKey: RNZQJBGGHJRVEB-UHFFFAOYSA-N

物化性质

• 沸点：
  401.7±45.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 重原子数：
  18.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  72.83
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-4-oxo-4-(2-methoxyphenyl)but-2-enoic acid ethyl ester 在 盐酸羟胺 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 50.75h， 生成 N-(1-adamantyl)-5-(2-methoxyphenyl)isoxazole-3-carboxamide
  参考文献：
  名称：

  3-Carboxamido-5-aryl-isoxazoles as new CB2 agonists for the treatment of colitis

  摘要：

  Recent investigations showed that anandamide, the main endogenous ligand of CB1 and CB2 cannabinoid receptors, possesses analgesic, antidepressant and anti-inflammatory effects. In the perspective to treat inflammatory bowel disease (IBD), our approach was to develop new selective CB2 receptor agonists without psychotropic side effects associated to CB1 receptors. In this purpose, a new series of 3-carboxamido-5-aryl-isoxazoles, never described previously as CB2 receptor agonists, was designed, synthesized and evaluated for their biological activity. The pharmacological results have identified great selective CB2 agonists with in vivo anti-inflammatory activity in a DSS-induced acute colitis mouse model. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.010
• 作为产物：
  描述：

  2'-羟基苯乙酮 在 sodium ethanolate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 2-hydroxy-4-oxo-4-(2-methoxyphenyl)but-2-enoic acid ethyl ester
  参考文献：
  名称：

  3-Carboxamido-5-aryl-isoxazoles as new CB2 agonists for the treatment of colitis

  摘要：

  Recent investigations showed that anandamide, the main endogenous ligand of CB1 and CB2 cannabinoid receptors, possesses analgesic, antidepressant and anti-inflammatory effects. In the perspective to treat inflammatory bowel disease (IBD), our approach was to develop new selective CB2 receptor agonists without psychotropic side effects associated to CB1 receptors. In this purpose, a new series of 3-carboxamido-5-aryl-isoxazoles, never described previously as CB2 receptor agonists, was designed, synthesized and evaluated for their biological activity. The pharmacological results have identified great selective CB2 agonists with in vivo anti-inflammatory activity in a DSS-induced acute colitis mouse model. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.010

文献信息

• New selective carbonic anhydrase IX inhibitors: Synthesis and pharmacological evaluation of diarylpyrazole-benzenesulfonamides
  作者：Tiphaine Rogez-Florent、Samuel Meignan、Catherine Foulon、Perrine Six、Abigaëlle Gros、Christine Bal-Mahieu、Claudiu T. Supuran、Andrea Scozzafava、Raphaël Frédérick、Bernard Masereel、Patrick Depreux、Amélie Lansiaux、Jean-François Goossens、Sébastien Gluszok、Laurence Goossens

  DOI：10.1016/j.bmc.2012.10.029

  日期：2013.3

  Carbonic anhydrase (CA) IX expression is increased upon hypoxia and has been proposed as a therapeutic target since it has been associated with poor prognosis, tumor progression and pH regulation. We report the synthesis and the pharmacological evaluation of a new class of human carbonic anhydrase (hCA) inhibitors, 4-(5-aryl-2-hydroxymethyl-pyrazol-1-yl)-benzenesulfonamides. A molecular modeling study

  碳酸酐酶（CA）IX的表达在缺氧时增加，并且由于与不良预后，肿瘤进展和pH调节相关，因此被提议作为治疗靶标。我们报告了新型的人类碳酸酐酶（hCA）抑制剂4-（5-芳基-2-羟甲基-吡唑-1-基）-苯磺酰胺类的合成和药理学评估。为了模拟这种新的酶抑制剂家族在hCA IX活性位点内的结合模式，进行了分子建模研究。药理研究表明，在参数纳摩尔范围内，hCA IX的抑制力很高。这项研究表明磺酰胺基在间位上的位置1-苯基吡唑的相对于我们的化合物的hCA II的选择性增加了hCA IX。使用阿霉素作为细胞毒剂并在选定的CA IX抑制剂存在下，对乳腺癌MDA-MB-231细胞进行了体外抗增殖筛选。结果表明，用1μMCA IX抑制剂将阿霉素在低氧环境中的细胞毒性效率（以IC 50值表示）恢复到20％的水平。
• “On water” synthesis of N-unsubstituted pyrazoles: semicarbazide hydrochloride as an alternative to hydrazine for preparation of pyrazole-3-carboxylate derivatives and 3,5-disubstituted pyrazoles
  作者：Violeta Marković、Milan D. Joksović

  DOI：10.1039/c4gc02028f

  日期：——

  A green, simple and highly efficient method for the synthesis of pyrazole-3-carboxylates and 3,5-disubstituted pyrazoles by cyclization of 4-aryl(hetaryl, alkyl)-2,4-diketoesters and 1,3-diketones with semicarbazide hydrochloride under “on water” conditions has been developed. This method also does not require toxic hydrazine and product purification, eliminating the use of toxic liquid chemicals.

  一种绿色，简单且高效的方法，通过用氨基脲盐酸盐将4-芳基（杂芳基，烷基）-2,4-二酮酸酯和1,3-二酮环化，合成吡唑-3-羧酸酯和3,5-二取代的吡唑在“水上”条件下已经开发出来。该方法也不需要毒性肼和产物纯化，从而消除了对有毒液体化学物质的使用。
• An enolate ion as a synthon in biocatalytic synthesis of 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: lemon juice as an alternative to hazardous solvents and catalysts
  作者：Jelena Petronijević、Zorica Bugarčić、Goran A. Bogdanović、Srđan Stefanović、Nenad Janković

  DOI：10.1039/c6gc02893d

  日期：——

  Innovative, efficient, clean, experimentally simple and environmentally friendly one-pot biocatalytic synthesis of two small libraries of novel 3,4-dihydro-2(1H)-quinoxalinones (4a-m) and 3,4-dihydro-1,4-benzoxazin-2-ones (5a, 5b, 5f and 5k-o) by heterocyclization of ethyl...

  创新，高效，清洁，实验简单且环境友好的一锅式生物催化合成两个新颖的3,4-dihydro-2（1H）-quinoxalinones（4a-m）和3,4-dihydro-1,4-小文库苯并恶嗪-2-酮（5a，5b，5f和5k-o）是通过乙基...
• Discovery of Membrane-Bound Pyrophosphatase Inhibitors Derived from an Isoxazole Fragment
  作者：Niklas G. Johansson、Ainoleena Turku、Keni Vidilaseris、Loïc Dreano、Ayman Khattab、Daniel Ayuso Pérez、Aaron Wilkinson、Yuezhou Zhang、Matti Tamminen、Evgeni Grazhdankin、Alexandros Kiriazis、Colin W. G. Fishwick、Seppo Meri、Jari Yli-Kauhaluoma、Adrian Goldman、Gustav Boije af Gennäs、Henri Xhaard

  DOI：10.1021/acsmedchemlett.9b00537

  日期：2020.4.9

  Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of small mPPase inhibitors with 6-10 mu M IC50 values in the Thermotoga maritima test system. Promisingly, the compounds retained activity against Plasmodium falciparum mPPase in membranes and inhibited parasite growth.
• 3-Aroylmethylene-2,3,6,7-tetrahydro-1<i>H</i>-pyrazino[2,1-<i>a</i>]isoquinolin-4(11b<i>H</i>)-ones as Potent Nrf2/ARE Inducers in Human Cancer Cells and AOM-DSS Treated Mice
  作者：Mei-yang Xi、Jian-min Jia、Hao-peng Sun、Zhong-ying Sun、Jie-wei Jiang、Ya-jing Wang、Min-ye Zhang、Jun-feng Zhu、Li-li Xu、Zheng-yu Jiang、Xin Xue、Ming Ye、Xi Yang、Yuan Gao、Lei Tao、Xiao-ke Guo、Xiao-li Xu、Qing-long Guo、Xiao-jin Zhang、Rong Hu、Qi-dong You

  DOI：10.1021/jm400944k

  日期：2013.10.24

  Nrf2-mediated activation of ARE regulates expression of cytoprotective enzymes against oxidative stress, inflammation, and carcinogenesis. We have discovered a novel structure (1) as an ARE inducer via luciferase reporter assay to screen the in-house database of our laboratory. The potency of 1 was evaluated by the expression of NQO-1, HO-1, and nuclear translocation of Nrf2 in HCT116 cells. In vivo potency of 1 was studied using AOM-DSS models, showing that the development of colorectal adenomas was significantly inhibited. Administration with 1 lowered the expression of IL-6, IL-1 beta, and promoted Nrf2 nuclear translocation. These results indicated that 1 is a potent Nrf2/ARE activator, both in vitro and in vivo. Forty-one derivatives were synthesized for SAR study, and a more potent compound 17 was identified. To our knowledge, this is a potent ARE activator. Besides, its novel structure makes it promising for further optimization.