ethyl 2-acetyl-4-(4-biphenylyl)-4-oxobutanoate | 63472-36-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-acetyl-4-(4-biphenylyl)-4-oxobutanoate
• 英文别名: 2-(4-Phenyl-phenacyl)-acetessigsaeure-aethylester；ethyl 2-acetyl-4-oxo-4-(4-phenylphenyl)butanoate
• CAS: 63472-36-6
• 化学式: C₂₀H₂₀O₄
• 分子量: 324.376
• InChiKey: DPHOVIOTYOBQBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  24.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  60.44
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-acetyl-4-(4-biphenylyl)-4-oxobutanoate 在 氢氧化钾 、 乙醇 作用下， 以 溶剂黄146 为溶剂， 反应 1.0h， 生成 3-methyl-isoxazole-5-carboxylic acid 2-biphenyl-4-yl-5-methyl-pyrrol-1-ylamide
  参考文献：
  名称：

  Fatutta,S., Gazzetta Chimica Italiana, 1960, vol. 90, p. 1645 - 1657

  摘要：

  DOI：
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 2-溴-4-苯基乙酰苯 在 sodium 作用下， 以 乙醚 为溶剂， 生成 ethyl 2-acetyl-4-(4-biphenylyl)-4-oxobutanoate
  参考文献：
  名称：

  Fatutta,S., Gazzetta Chimica Italiana, 1960, vol. 90, p. 1645 - 1657

  摘要：

  DOI：

文献信息

• Fenbufen, a New Anti-Inflammatory Analgesic: Synthesis and Structure-Activity Relationships of Analogs
  作者：Ralph G. Child、Arnold C. Osterberg、Adolph E. Sloboda、Andrew S. Tomcufcik

  DOI：10.1002/jps.2600660403

  日期：1977.4

  hundred analogs of fenbufen were prepared and tested using the carrageenan, polyarthritis, and UV erythema anti-inflammatory tests and the 2-phenyl-1,4-benzoquinone writhing and inflamed paw pressure analgesic tests. Only three retained the same full spectrum of activity as fenbufen: dl-4-(4-biphenylyl)-4-hydroxybutyric acid, dl-4-(4-biphenylyl)-1,4-butanediol, and 4-biphenylacetic acid. Fenbufen had the

  制备了一百个芬布芬类似物，并使用角叉菜胶，多关节炎和紫外线红斑抗炎试验以及2-苯基-1,4-苯醌扭转和发炎的爪压镇痛试验进行了测试。只有三个保留了与芬布芬相同的全范围活性：dl-4-（4-联苯基）-4-羟基丁酸，dl-4-（4-联苯基）-1,4-丁二醇和4-联苯乙酸。在这五项测试中，芬布芬的活性谱与阿司匹林，苯基丁a和消炎痛相同。此外，剂量反应衍生的药效在所有五个试验中均显示出芬布芬比阿司匹林更有效，并且至少与苯基丁a同样有效。两种相关化合物通常相似。
• Bijev, Atanas; Nankov, Atanas; Keuleyan, Emma, Arzneimittel-Forschung/Drug Research, 2004, vol. 54, # 2, p. 119 - 124
  作者：Bijev, Atanas、Nankov, Atanas、Keuleyan, Emma、Markovska, Rumiana、Daneva, Elitsa

  DOI：——

  日期：——
• Design, solid-phase synthesis, and biological evaluation of novel 1,5-diarylpyrrole-3-carboxamides as carbonic anhydrase IX inhibitors
  作者：Sébastien Gluszok、Raphaël Frédérick、Catherine Foulon、Frédérique Klupsch、Claudiu T. Supuran、Daniela Vullo、Andrea Scozzafava、Jean-François Goossens、Bernard Masereel、Patrick Depreux、Laurence Goossens

  DOI：10.1016/j.bmc.2010.09.007

  日期：2010.11

  Following previous studies we herein report the synthesis and the pharmacological evaluation of a new class of human carbonic anhydrase (hCA) inhibitors, 1,5-diarylpyrrole-3-carboxamides prepared by a solid-phase strategy involving a PS(HOBt) resin. A molecular modeling study was conducted in order to simulate the binding mode of this new family of enzyme inhibitors within the active site of hCA IX. This study revealed that the 3-position of the pyrrole was opened to the solvent, so we introduced an amino side-chain, protonated at physiological pH both to enhance the aqueous solubility and to decrease the cell membrane penetration. This strategy consisted of preparing membrane-impermeant inhibitors that may selectively target the tumor-associated hCA IX. Physico-chemical characterizations including aqueous solubility and lipophilic parameters are described. Pharmacological studies revealed high hCA IX inhibitory potency in the nanomolar range. Some compounds are selective for hCA IX displaying hCA I/hCA IX and hCA II/hCA IX ratios higher than 20 and 5, respectively. (C) 2010 Elsevier Ltd. All rights reserved.