methyl ­1-­(4-­isobutylphenyl)cyclopropanecarboxylate | 1393566-61-4

• 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 ­1-­(4-­isobutylphenyl)cyclopropanecarboxylate
• 英文别名: methyl 1-(4-isobutylphenyl)cyclopropane-1-carboxylate；methyl 1-(4-isobutylphenyl)cyclopropanecarboxylate；Methyl 1-[4-(2-methylpropyl)phenyl]cyclopropane-1-carboxylate
• CAS: 1393566-61-4
• 化学式: C₁₅H₂₀O₂
• 分子量: 232.323
• InChiKey: XEXOAMULHLABMT-UHFFFAOYSA-N

物化性质

• 沸点：
  308.4±21.0 °C(Predicted)
• 密度：
  1.057±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl ­1-­(4-­isobutylphenyl)cyclopropanecarboxylate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以90%的产率得到1-(4-isobutylphenyl)cyclopropanecarboxylic acid
  参考文献：
  名称：

  探索布洛芬新型酰胺衍生物的脂肪酸酰胺水解酶和环氧合酶抑制特性。

  摘要：

  脂肪酸酰胺水解酶（FAAH）的抑制作用可减少实验动物中非甾体抗炎药如舒林酸和消炎痛对胃肠道造成的损害，这表明FAAH环氧合酶（COX）双重作用抑制剂可能具有有用的治疗特性。在这里，我们研究了布洛芬的12种新型酰胺类似物作为潜在的双重作用FAAH / COX抑制剂。发现N-（3-溴吡啶-2-基）-2-（4-异丁基苯基）丙酰胺（Ibu-AM68）通过可逆的混合型抑制机制抑制大鼠脑匀浆[3H] anandamide的水解。 Ki值为0.26 µM，α值为4.9。浓度为10 µM时，该化合物不会抑制绵羊COX-1或人重组COX-2对花生四烯酸的环氧化作用。然而，此浓度的Ibu-AM68大大降低了COX-2催化内源性大麻素2-花生四烯酰甘油的环氧化作用的能力。结论是，Ibu-AM68是双作用FAAH /底物选择性COX抑制剂。

  DOI：

  10.1080/14756366.2020.1743283
• 作为产物：
  描述：

  异丁芬酸 在 盐酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.75h， 生成 methyl ­1-­(4-­isobutylphenyl)cyclopropanecarboxylate
  参考文献：
  名称：

  探索布洛芬新型酰胺衍生物的脂肪酸酰胺水解酶和环氧合酶抑制特性。

  摘要：

  脂肪酸酰胺水解酶（FAAH）的抑制作用可减少实验动物中非甾体抗炎药如舒林酸和消炎痛对胃肠道造成的损害，这表明FAAH环氧合酶（COX）双重作用抑制剂可能具有有用的治疗特性。在这里，我们研究了布洛芬的12种新型酰胺类似物作为潜在的双重作用FAAH / COX抑制剂。发现N-（3-溴吡啶-2-基）-2-（4-异丁基苯基）丙酰胺（Ibu-AM68）通过可逆的混合型抑制机制抑制大鼠脑匀浆[3H] anandamide的水解。 Ki值为0.26 µM，α值为4.9。浓度为10 µM时，该化合物不会抑制绵羊COX-1或人重组COX-2对花生四烯酸的环氧化作用。然而，此浓度的Ibu-AM68大大降低了COX-2催化内源性大麻素2-花生四烯酰甘油的环氧化作用的能力。结论是，Ibu-AM68是双作用FAAH /底物选择性COX抑制剂。

  DOI：

  10.1080/14756366.2020.1743283

文献信息

• Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes
  作者：Matthew A. Windsor、Daniel J. Hermanson、Philip J. Kingsley、Shu Xu、Brenda C. Crews、Winnie Ho、Catherine M. Keenan、Surajit Banerjee、Keith A. Sharkey、Lawrence J. Marnett

  DOI：10.1021/ml3001616

  日期：2012.9.13

  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.
• 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.