4-苯氧基苯甲酸乙酯 | 31994-68-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-苯氧基苯甲酸乙酯
• 英文名称: 4-phenoxybenzoic acid ethyl ester
• 英文别名: ethyl 4-phenoxybenzoate；4-Phenoxy-benzoesaeure-aethylester；p-Phenoxybenzoic acid ethyl ester
• CAS: 31994-68-0
• 化学式: C₁₅H₁₄O₃
• mdl: MFCD00496636
• 分子量: 242.274
• InChiKey: GJDBBHASMUCGME-UHFFFAOYSA-N

物化性质

• 沸点：
  152-154 °C(Press: 0.4 Torr)
• 密度：
  1.1171 g/cm3(Temp: 40 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-苯氧基苯甲酸乙酯 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以89%的产率得到4-苯氧基苯甲酸
  参考文献：
  名称：

  对 SIRT 的芳氧基苯甲酰胺衍生物虚拟筛选命中的 Hit-to-lead 优化

  摘要：

  Sirtuins (SIRTs) 是一类烟酰胺腺嘌呤二核苷酸 (NAD + ) 依赖性蛋白组蛋白脱乙酰酶 (HDAC)，从细菌到哺乳动物都进化保守。这组酶使用 NAD +作为共底物催化组蛋白或非组蛋白底物中赖氨酸残基的可逆脱乙酰化。大量研究表明，SIRT 的异常酶活性与糖尿病、癌症和神经退行性疾病等多种疾病有关。之前，我们进行了基于药效团的虚拟筛选活动和芳氧基苯甲酰胺衍生物 ( 1) 显示 SIRT1/2 抑制作用被确定为命中化合物。在当前的研究中，探索了对命中化合物的hit-to-lead优化以改善SIRT结合和抑制。已经合成了 14 种化合物，其中 10 种是新化合物，并对其对 SIRT1-3 的抑制活性进行了体外生物学评估。通过进行结构修饰，与命中化合物相比，观察到ST01、ST02和ST11 的选择性 SIRT1 抑制显着改善。对于ST14观察到最高的 SIRT2 抑制活性，这是根据与为

  DOI：

  10.1016/j.bmc.2020.115961
• 作为产物：
  描述：

  4-苯氧基苯甲酸 在 乙醇 、 硫酸 作用下， 反应 8.0h， 生成 4-苯氧基苯甲酸乙酯
  参考文献：
  名称：

  Discovering Potent Inhibitors Against the β-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) of Helicobacter pylori: Structure-Based Design, Synthesis, Bioassay, and Crystal Structure Determination

  摘要：

  The discovery of HpFabZ inhibitors is now of special interest in the treatment of various gastric diseases. In this work, three series of derivatives (compounds 3, 4, and 5) were designed, synthesized, and their biological activities were investigated as potential HpFabZ inhibitors in a two phased manner. First, we designed and synthesized two series of derivatives (3a-r and 4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k, 3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2 muM. Second, a focused combinatorial library containing 280 molecules was designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was 46 times higher than that of the hit 1. The high hit rate and the potency of the new HpFabZ inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening.

  DOI：

  10.1021/jm8015602

文献信息

• Fe3O4@mesoporouspolyaniline: A Highly Efficient and Magnetically Separable Catalyst for Cross-Coupling of Aryl Chlorides and Phenols
  作者：R. Arundhathi、D. Damodara、Pravin R. Likhar、M. Lakshmi Kantam、P. Saravanan、Travis Magdaleno、Sun Hee Kwon

  DOI：10.1002/adsc.201000977

  日期：2011.6

  A high surface, magnetic Fe3O4@mesoporouspolyaniline core‐shell nanocomposite was synthesized from magnetic iron oxide (Fe3O4) nanoparticles and mesoporouspolyaniline (mPANI). The novel porous magnetic Fe3O4 was obtained by solvothermal method under sealed pressure reactor at high temperature to achieve high surface area. The mesoporouspolyaniline shell was synthesized by in situ surface polymerization

  由磁性氧化铁（Fe 3 O 4）纳米颗粒和介孔聚苯胺（mPANI）合成了高表面磁性Fe 3 O 4 @介孔聚苯胺核壳纳米复合材料。在密闭压力反应器中，在高温下通过溶剂热法获得了新型的多孔磁性Fe 3 O 4，从而获得了较大的表面积。通过在多孔磁性Fe 3 O 4上原位表面聚合合成介孔聚苯胺壳在聚乙烯吡咯烷酮（PVP）和十二烷基苯磺酸钠（SDBS）作为连接剂和结构导向剂的情况下，通过“黑莓纳米结构”组装。如各种表征技术所证实的，材料组成，化学计量比和反应条件在这些纳米结构的合成中起着至关重要的作用。中孔聚苯胺壳的作用是稳定多孔磁性Fe 3 O 4纳米颗粒，并提供直接进入核心Fe 3 O 4纳米颗粒的通道。在芳基氯和苯酚的交叉偶联中评估了磁性Fe 3 O 4 @mesoporousPANI纳米复合材料的催化活性。
• Modular Synthesis of Arylacetic Acid Esters, Thioesters, and Amides from Aryl Ethers via Rh(II)-Catalyzed Diazo Arylation
  作者：Daniel Best、Mickaël Jean、Pierre van de Weghe

  DOI：10.1021/acs.joc.6b01426

  日期：2016.9.2

  One-pot formation of arylacetic acid esters, thioesters, and amides via Rh(II)-catalyzed arylation of a Meldrum’s acid-derived diazo reagent with electron-rich arenes is described. The methodology was used to efficiently synthesize an anticancer compound.

  描述了通过Rh（II）催化的Meldrum酸衍生的重氮试剂与富电子芳烃的一锅法形成的芳基酸酯，硫酯和酰胺。该方法用于有效合成抗癌化合物。
• Design, synthesis and evaluation of novel molecules with a diphenyl ether nucleus as potential antitubercular agents
  作者：Yinghong Yang、Zhenling Wang、Jianzhong Yang、Tao Yang、Weiyi Pi、Wei Ang、Yanni Lin、Yuanyuan Liu、Zicheng Li、Youfu Luo、Yuquan Wei

  DOI：10.1016/j.bmcl.2011.12.022

  日期：2012.1

  A series of compounds with a diphenyl ether nucleus were synthesized by incorporating various amines into the diphenyl ether scaffold with an amide bond. Their antitubercular activities were evaluated against Mycobacterium tuberculosis H37Rv by a microdilution method, with MIC values ranging from 4 to 64 μg/mL. Through structure–activity relationship studies, the two chlorine atoms at 3 and 4 positions

  通过将各种胺掺入具有酰胺键的二苯醚支架中，合成了一系列具有二苯醚核的化合物。通过微稀释法评估了它们的抗结核分枝 杆菌H 37 Rv的抗结核活性，MIC值为4至64μg/ mL。通过结构-活性关系研究，发现R 2基团的苯环的3和4位上的两个氯原子在抗结核活性中起重要作用。最有效的化合物6c通过MTT分析在HepG2细胞系中的MIC值为4μg/ mL，并具有良好的安全性。化合物6c 进一步发现其在卡介苗感染的小鼠模型中有效，为后续优化提供了良好的线索。
• First palladium-catalyzed denitrated coupling reaction of nitroarenes with phenols
  作者：Hailei Wang、Ajuan Yu、Aijuan Cao、Junbiao Chang、Yangjie Wu

  DOI：10.1002/aoc.3043

  日期：2013.10

  The first palladium‐catalyzed protocol for the denitrated coupling reaction of nitroarenes with phenols has been developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. The cyclopalladated ferrocenylimine (catalyst Ic) exhibited highly catalytic activity for this transformation with low catalyst loading (0.75 mol%) and short reaction time (2 h). The efficiency of this reaction

  已经开发出了第一个钯催化的硝基芳烃与苯酚的脱硝偶联反应方案，以中等到极好的收率获得了不对称的二芳基醚。环钯的二茂铁基亚胺（催化剂Ic）对这种转化反应显示出很高的催化活性，催化剂负载量低（0.75摩尔％），反应时间短（2小时）。该反应与一系列基团的相容性证明了该反应的效率。此外，在这些转换中不需要严格排除空气或湿气。版权所有©2013 John Wiley＆Sons，Ltd.
• Structure-based design, structure–activity relationship analysis, and antitumor activity of diaryl ether derivatives
  作者：Shao-Mei Yang、Zhi-Ning Huang、Zhong-Shi Zhou、Jin Hou、Man-Yi Zheng、Li-Juan Wang、Yu Jiang、Xin-Yi Zhou、Qiu-Yue Chen、Shan-Hua Li、Fu-Nan Li

  DOI：10.1007/s12272-015-0578-7

  日期：2015.10

  To identify novel therapeutic agents to treat cancer, we synthesized a series of diaryl ether derivatives. Structure–activity relationship studies revealed that the presence of a chlorine or hydroxyl at the para-position on the phenyl ring (5h or 5k) significantly enhanced antitumor activity. Compound 5h had stronger growth inhibitory activity in HepG2, A549, and HT-29 cells than compound 5k, with IC50 values of 2.57, 5.48, and 30.04 μM, respectively. Compound 5h also inhibited the growth of other cells lines, including Hep3B, PLC/PRF5, SMMC-7721, HeLa, and A375, with IC50 values of 2.76, 4.26, 29.66, 18.86, and 10.21 μM, respectively. The antitumor activity of compound 5h was confirmed by a colony forming assay. Further, our results indicated that the antitumor activity of compound 5h may be mediated by enhancing expression of p21 and cl-caspase3, and leading to apoptosis of cancer cells.

  为了发现新的抗癌药物，我们合成了一系列二苯醚衍生物。结构-活性关系研究表明，在苯环的对位引入氯或羟基（如5h或5k）显著增强了抗肿瘤活性。化合物5h在HepG2、A549和HT-29细胞中的生长抑制活性强于化合物5k，其IC50值分别为2.57、5.48和30.04 μM。化合物5h还能抑制其他细胞系的生长，包括Hep3B、PLC/PRF5、SMMC-7721、HeLa和A375，其IC50值分别为2.76、4.26、29.66、18.86和10.21 μM。化合物5h的抗肿瘤活性通过集落形成实验得到了验证。进一步的结果表明，化合物5h的抗肿瘤活性可能是通过上调p21和cl-caspase3的表达，并诱导癌细胞凋亡来介导的。