methyl ­1-­(6-­methoxynaphthalen-­2-­yl)cyclopropanecarboxylate | 1393566-60-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl ­1-­(6-­methoxynaphthalen-­2-­yl)cyclopropanecarboxylate
• 英文别名: methyl 1-(6-methoxynaphthalen-2-yl)cyclopropanecarboxylate；Methyl 1-(6-methoxynaphthalen-2-yl)cyclopropane-1-carboxylate；methyl 1-(6-methoxynaphthalen-2-yl)cyclopropane-1-carboxylate
• CAS: 1393566-60-3
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: CPKICSFZMDUSQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 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：

  methyl ­1-­(6-­methoxynaphthalen-­2-­yl)cyclopropanecarboxylate 在 potassium trimethylsilonate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以78%的产率得到1-(6-methoxynaphthalen-2-yl)cyclopropanecarboxylic acid
  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：

  6-甲氧基-2-萘甲醛 在 sodium chlorite 、 potassium dihydrogenphosphate 、 2,3-二甲基-2-丁烯 、 硫酸 、 potassium tert-butylate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 6.48h， 生成 methyl ­1-­(6-­methoxynaphthalen-­2-­yl)cyclopropanecarboxylate
  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

文献信息

• [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
• COMPOSITIONS AND METHODS FOR SUBSTRATE-SELECTIVE INHIBITION OF ENDOCANNABINOID OXYGENATION
  申请人：Vanderbilt University

  公开号：US20150183737A1

  公开（公告）日：2015-07-02

  Methods for selectively inhibiting endocannabinoid oxygenation but not arachidonic acid oxygenation. In some embodiments, the methods include contacting a COX-2 polypeptide with an effective amount of a substrate-selective COX-2 inhibitor. Also provided are methods for elevating a local endogenous cannabinoid concentrations; methods of reducing depletion of an endogenous cannabinoid; methods for inducing analgesia; methods of providing anxiolytic therapy; methods for providing anti-depressant therapy; and compositions for performing the disclosed methods.
• [EN] COMPOSITIONS AND METHODS FOR 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：WO2014015341A2

  公开（公告）日：2014-01-23

  Methods for selectively inhibiting endocannabinoid oxygenation but not arachidonic acid oxygenation. In some embodiments, the methods include contacting a COX-2 polypeptide with an effective amount of a substrate-selective COX-2 inhibitor. Also provided are methods for elevating a local endogenous cannabinoid concentrations; methods of reducing depletion of an endogenous cannabinoid; methods for inducing analgesia; methods of providing anxiolytic therapy; methods for providing anti-depressant therapy; and compositions for performing the disclosed methods.