benzyl 2-(4-(2-tert-butoxy-2-oxoethoxy)phenoxy)acetate | 1221895-22-2

• 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: benzyl 2-(4-(2-tert-butoxy-2-oxoethoxy)phenoxy)acetate
• 英文别名: benzyl tert-butyl 2,20-[benzene-1,4-diylbis(oxy)]diacetate；Benzyl 2-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenoxy]acetate
• CAS: 1221895-22-2
• 化学式: C₂₁H₂₄O₆
• 分子量: 372.418
• InChiKey: WKWRAYOJBYWTTJ-UHFFFAOYSA-N

物化性质

• 沸点：
  480.3±30.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl 2-(4-(2-tert-butoxy-2-oxoethoxy)phenoxy)acetate 在 palladium 10% on activated carbon 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 反应 12.0h， 生成 tert-butyl 2-(4-(2-((S)-1-((S)-2-((S)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethoxy)phenoxy)acetate
  参考文献：
  名称：

  Human Neutrophil Elastase Phosphonic Inhibitors with Improved Potency of Action

  摘要：

  Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of alpha-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a k(inact)/K-1 of 2353000 M-1 s(-1), which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.

  DOI：

  10.1021/jm300599x
• 作为产物：
  描述：

  溴乙酸叔丁酯 在 sodium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 benzyl 2-(4-(2-tert-butoxy-2-oxoethoxy)phenoxy)acetate
  参考文献：
  名称：

  使用组合化学选择有效的HTRA3激活剂

  摘要：

  在此，我们报告了能够提高HtrA3（高温要求A）蛋白酶的蛋白水解活性的拟肽文库的选择，合成和酶促评估。合成修饰五肽溶液中的迭代解卷积产生了两个有效的HtrA3激活剂，它们在微摩尔范围内起作用（HCOO-CH 2 O-C 6 H 4 -OCH 2 -CO-Tyr-Asn-Phe-His-Asn-OH和HCOO-CH 2 O-C 6 H 4 -OCH 2 -CO-Tyr-Asn-Phe-His-Glu-OH）。两种化合物均以选择性方式使人工HtrA3底物的蛋白水解增加40倍以上。在分子建模的基础上，所选化合物与PDZ结构域牢固结合。

  DOI：

  10.1021/acscombsci.7b00051

文献信息

• Development of a highly water-soluble peptide-based human neutrophil elastase inhibitor; AE-3763 for treatment of acute organ injury
  作者：Yasunao Inoue、Tomoki Omodani、Ryotaro Shiratake、Hiroshi Okazaki、Akemi Kuromiya、Taeko Kubo、Fuminori Sato

  DOI：10.1016/j.bmc.2009.09.020

  日期：2009.11

  A series of peptide-based transition-state human neutrophil elastase (HNE) inhibitors with N-terminal acidic moieties were synthesized and their inhibitory activity against HNE was evaluated both in vitro and in vivo. Our results show that compounds containing cyclic amide bridged acidic moieties at the N-terminal have not only improved water solubility but also high in vivo potency. Among these compounds, AE-3763 showed remarkable efficacy in hamster models of elastase-induced lung hemorrhage and lipopolysaccharide (LPS)-induced lung injury as well as in a mouse model of LPS/galactosamine-induced acute multiple organ dysfunctions. The water solubility of AE-3763 (>1000 mg/ml in H(2)O) was also far superior to that of any of the other compounds synthesized. Thus, it is believed that AE-3763 would be useful for treatment of HNE-associated respiratory disorders, such as acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and acute exacerbation of chronic obstructive pulmonary disease (COPD). (C) 2009 Elsevier Ltd. All rights reserved.