methyl 2-­(2-­fluoro-­[1,1'-­biphenyl]-­4-­yl)-­2-­methylpropanoate

• 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-­[1,1'-­biphenyl]-­4-­yl)-­2-­methylpropanoate
• 英文别名: methyl 2-(2-fluoro-[1,1'-biphenyl]-4-yl)-2-methylpropanoate；methyl α-(3-fluoro-4-phenylphenyl)isobutyrate；methyl 2-(2-fluoro-biphenyl-4-yl)-2-methyl-propionate；methyl 2-(3-fluoro-4-phenylphenyl)-2-methylpropanoate
• 化学式: C₁₇H₁₇FO₂
• 分子量: 272.319
• InChiKey: IPWJPMDVLDFHOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-­(2-­fluoro-­[1,1'-­biphenyl]-­4-­yl)-­2-­methylpropanoate 在 potassium trimethylsilonate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以84%的产率得到Methylflurbiprofen
  参考文献：
  名称：

  Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes

  摘要：

  Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 mu M for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.

  DOI：

  10.1021/ml3001616
• 作为产物：
  描述：

  氟比洛芬 在 N,N-二甲基丙烯基脲 、 硫酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 methyl 2-­(2-­fluoro-­[1,1'-­biphenyl]-­4-­yl)-­2-­methylpropanoate
  参考文献：
  名称：

  The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer’s disease modifying agent

  摘要：

  The subtle modification of a selection of A beta(42) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining A beta(42) inhibition. Methylflurbiprofen 6 exhibited similar in vitro A beta(42) inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer's disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clinical development. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.033

文献信息

• Efficient Synthesis of α-Aryl Esters by Room-Temperature Palladium-Catalyzed Coupling of Aryl Halides with Ester Enolates
  作者：Morten Jørgensen、Sunwoo Lee、Xiaoxiang Liu、Joanna P. Wolkowski、John F. Hartwig

  DOI：10.1021/ja027643u

  日期：2002.10.1

  arylation of alpha,alpha-disubstituted esters were developed with LiNCy(2) as base and P(t-Bu)(3) as ligand. In addition, tert-butyl esters, such as those of Naproxen and Flurbiprofen, were prepared from tert-butyl propionate and aryl bromides in high yields in the presence of Pd(dba)(2) and the hindered, saturated heterocyclic carbene ligand precursor.

  催化量的 Pd(dba)(2) 由卡宾前体 N,N'-双(2,6-二异丙基苯基)-4,5-二氢咪唑鎓 (1) 或 P(t-Bu)(3) 介导芳基卤化物和酯烯醇化物在室温下以高产率偶联产生α-芳基酯。该反应对芳基卤化物上的官能团和取代模式具有高度耐受性。使用 LiNCy(2) 作为基础和 P(t-Bu)(3) 作为配体开发了用于选择性单芳基化乙酸叔丁酯和 α、α-二取代酯的有效芳基化的改进方案。此外，在 Pd(dba)(2) 和受阻饱和杂环卡宾配体前体存在下，由丙酸叔丁酯和芳基溴化物以高产率制备叔丁酯，例如萘普生和氟比洛芬。
• Isoxazole derivatives
  申请人：Sumitomo Pharmaceutical Company, Limited

  公开号：US06100260A1

  公开（公告）日：2000-08-08

  An isoxazole derivative represented by the formula: ##STR1## or a pharmaceutically acceptable salt thereof useful as a therapeutic drug for auto-immune diseases and inflammatory diseases.

  一种由以下结构表示的异噁唑衍生物：##STR1##或其药用可接受的盐，用作治疗自身免疫疾病和炎症性疾病的药物。
• PHARMACEUTICAL COMPOSITION AND METHOD
  申请人：Slade Rachel M.

  公开号：US20090155903A1

  公开（公告）日：2009-06-18

  The invention provides compounds, pharmaceutical compositions and methods for the therapeutic treatment and prevention of neurodegenerative disorder and other Aβ 42 -related diseases and disorders.

  该发明提供了化合物、制药组合物和方法，用于治疗和预防神经退行性疾病和其他与Aβ42相关的疾病和障碍。
• [EN] SUBSTRATE-SELECTIVE INHIBITION OF ENDOCANNABINOID OXYGENATION<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR UNE INHIBITION SÉLECTIVE DU SUBSTRAT DE L'OXYGÉNATION DES ENDOCANNABINOÏDES
  申请人：UNIV VANDERBILT

  公开号：WO2014015341A3

  公开（公告）日：2015-07-16
• ISOXAZOLE DERIVATIVES
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：EP0979226B1

  公开（公告）日：2005-11-09