methyl 2-(2-fluoro-4'-hydroxybiphenyl-4-yl)propanoate | 482294-50-8

• 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: methyl 2-(2-fluoro-4'-hydroxybiphenyl-4-yl)propanoate
• 英文别名: Methyl 2-(2-fluoro-4'-hydroxy-[1,1'-biphenyl]-4-yl)propanoate；methyl 2-[3-fluoro-4-(4-hydroxyphenyl)phenyl]propanoate
• CAS: 482294-50-8
• 化学式: C₁₆H₁₅FO₃
• 分子量: 274.292
• InChiKey: IHFRHCUSQCZWJI-UHFFFAOYSA-N

物化性质

• 熔点：
  104-105 °C
• 沸点：
  374.5±37.0 °C(predicted)
• 密度：
  1.206±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(2-fluoro-4'-hydroxybiphenyl-4-yl)propanoate 在 lithium hydroxide monohydrate 、 水 、 potassium carbonate 、 silver nitrate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 54.5h， 生成 6-{2'-fluoro-4'-[1-oxo-1-(4-(1,2,3,4-tetrahydroacridin-9-ylamino)butylamino)propan-2-yl]biphenyl-4-yloxy}hexyl nitrate
  参考文献：
  名称：

  NO-donating tacrine derivatives as potential butyrylcholinesterase inhibitors with vasorelaxation activity

  摘要：

  To search for potent anti-Alzheimer's disease (AD) agents with multifunctional effects, 12 NO-donating tacrine-flurbiprofen hybrid compounds (2a-l) were synthesized and biologically evaluated. It was found that all the new target compounds showed selective butyrylcholinesterase (BuChE) inhibitory activity in vitro comparable or higher than tacrine and the tacrine-flurbiprofen hybrid compounds 1a-c, and released moderate amount of NO in vitro. The kinetic study suggests that one of the most active and highest BuChE selective compounds 2d may not only compete with the substrate for the same catalytic active site (CAS) but also interact with a second binding site. Furthermore, 2d and 2l exhibited significant vascular relaxation effect, which is beneficial for the treatment of AD. All the results suggest that 2d and 2l might be promising lead compounds for further research. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.008
• 作为产物：
  描述：

  氟比洛芬 在 aluminum (III) chloride 、 硫酸 、 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 39.0h， 生成 methyl 2-(2-fluoro-4'-hydroxybiphenyl-4-yl)propanoate
  参考文献：
  名称：

  发现4'-OH-氟比洛芬曼尼希碱衍生物是具有多种抑制活性的潜在阿尔茨海默氏病治疗药物。

  摘要：

  设计，合成和评估了一系列4'-OH氟比洛芬曼尼希碱衍生物，作为治疗阿尔茨海默氏病的潜在多功能剂。生物学筛选结果表明，这些衍生物大多数表现出良好的多功能活性。其中，化合物8n对自诱导的Aβ1-42聚集表现出最佳的抑制作用（在25.0μM时为65.03％）。此外，该代表性化合物在体外还表现出良好的抗氧化活性，生物金属螯合能力和抗神经炎活性。此外，化合物8n显示出适当的血脑屏障渗透性。这些多功能特性突出了化合物8n作为抗AD多功能药物进一步开发的有希望的候选物。

  DOI：

  10.1016/j.bmc.2019.01.040

文献信息

• Site‐Selective C−H Oxygenation via Aryl Sulfonium Salts
  作者：Ruocheng Sang、Stamatis E. Korkis、Wanqi Su、Fei Ye、Pascal S. Engl、Florian Berger、Tobias Ritter

  DOI：10.1002/anie.201908718

  日期：2019.11.4

  Herein, we report a two-step process forming arene C-O bonds in excellent site-selectivity at a late-stage. The C-O bond formation is achieved by selective introduction of a thianthrenium group, which is then converted into C-O bonds using photoredox chemistry. Electron-rich, -poor and -neutral arenes as well as complex drug-like small molecules are successfully transformed into both phenols and various

  在此，我们报告了一种在后期以优异的位点选择性形成芳烃CO键的两步过程。CO 键的形成是通过选择性引入铊基团来实现的，然后使用光氧化还原化学将其转化为 CO 键。富电子、贫电子和中性芳烃以及复杂的类药物小分子被成功转化为酚类和各种醚类。该序列在概念上不同于所有先前的芳烃氧化反应，因为氧官能团可以在后期选择性地结合到复杂的小分子中，这尚未通过芳基卤化物显示出来。
• TEMPO-mediated late stage photochemical hydroxylation of biaryl sulfonium salts
  作者：Yue Zhao、Congjun Yu、Wenjing Liang、Iuliana L. Atodiresei、Frederic W. Patureau

  DOI：10.1039/d1cc07057f

  日期：——

  The late stage photochemical hydroxylation of biaryl sulfonium salts was enabled with a TEMPO derivative as a simple oxygen source, in metal free conditions.

  使用TEMPO衍生物作为简单的氧源，在无金属条件下实现了二芳基磺酸盐的晚期光化学羟基化。
• 一类羟基氟比洛芬曼尼希碱类化合物、其制备 方法和用途
  申请人：四川大学

  公开号：CN110003034B

  公开（公告）日：2021-06-18

  本发明公开了一类羟基氟比洛芬曼尼希碱类化合物（I）及其药学上可接受的盐、其制备方法、药物组合物和在制备治疗和/或预防神经退行性相关疾病药物中的用途，包括但不限于血管性痴呆、阿尔茨海默氏症、帕金森症、亨廷顿症、HIV相关痴呆症、多发性硬化症、进行性脊髓侧索硬化症、神经性疼痛、青光眼等神经退行性疾病；。
• Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies
  作者：Marco Migliore、Damien Habrant、Oscar Sasso、Clara Albani、Sine Mandrup Bertozzi、Andrea Armirotti、Daniele Piomelli、Rita Scarpelli

  DOI：10.1016/j.ejmech.2015.12.036

  日期：2016.2

  Non-steroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological effects by inhibiting cyclooxygenase (COX)-1 and COX-2. Though widely prescribed for pain and inflammation, these agents have limited utility in chronic diseases due to serious mechanism-based adverse events such as gastrointestinal damage. Concomitant blockade of fatty acid amide hydrolase (FAAH) enhances the therapeutic effects of the NSAIDs while attenuating their propensity to cause gastrointestinal injury. This favorable interaction is attributed to the accumulation of protective FAAH substrates, such as the endocannabinoid anandamide, and suggests that agents simultaneously targeting COX and FAAH might provide an innovative strategy to combat pain and inflammation with reduced side effects. Here, we describe the rational design and structure-active relationship (SAR) properties of the first class of potent multitarget FAAH-COX inhibitors. A focused SAR exploration around the prototype 10r (ARN2508) led to the identification of achiral (18b) as well as racemic (29a-c and 29e) analogs. Absolute configurational assignment and pharmacological evaluation of single enantiomers of 10r are also presented. (S)-(+)-10r is the first highly potent and selective chiral inhibitor of FAAH-COX with marked in vivo activity, and represents a promising lead to discover novel analgesics and anti-inflammatory drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis and Biological Activity of Flurbiprofen Analogues as Selective Inhibitors of β-Amyloid₁_-₄₂ Secretion
  作者：Ilaria Peretto、Stefano Radaelli、Carlo Parini、Michele Zandi、Luca F. Raveglia、Giulio Dondio、Laura Fontanella、Paola Misiano、Chiara Bigogno、Andrea Rizzi、Benedetta Riccardi、Marcello Biscaioli、Silvia Marchetti、Paola Puccini、Silvia Catinella、Ivano Rondelli、Valentina Cenacchi、Pier Tonino Bolzoni、Paola Caruso、Gino Villetti、Fabrizio Facchinetti、Elda Del Giudice、Nadia Moretto、Bruno P. Imbimbo

  DOI：10.1021/jm0502541

  日期：2005.9.1

  Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit beta-amyloid(1-42) (A beta 42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing A beta 42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on A beta 42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma A beta 42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.