2-(4-异丁基苯基)-2-甲基丙酸 | 95499-72-2

• 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: 2-(4-异丁基苯基)-2-甲基丙酸
• 英文名称: methylibuprofen
• 英文别名: 2-methyl-2-(p-isobutylphenyl)propionic acid；2-(4-isobutylphenyl)-2-methylpropanoic acid；2-(4-isobutyl-phenyl)-2-methyl propionic acid；Benzeneacetic acid, alpha,alpha-dimethyl-4-(2-methylpropyl)-；2-methyl-2-[4-(2-methylpropyl)phenyl]propanoic acid
• CAS: 95499-72-2
• 化学式: C₁₄H₂₀O₂
• 分子量: 220.312
• InChiKey: AZPUUNIFABPZND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2916399090

反应信息

• 作为反应物：
  描述：

  2-(4-异丁基苯基)-2-甲基丙酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 1.17h， 生成 N-hydroxy-N-methyl-2-methyl-2-<4-(2-methylpropyl)phenyl>propionamide
  参考文献：
  名称：

  5-脂氧合酶的异羟肟酸抑制剂的体内表征。

  摘要：

  可以将异羟肟酸功能性地掺入简单分子中以产生有效的5-脂氧合酶抑制剂。已经直接使用大鼠腹膜过敏模型测量了许多这些异羟肟酸酯在体内抑制白三烯合成的能力。尽管它们在体外具有强大的酶抑制活性，但许多口服异羟肟酸在体内仅能弱抑制白三烯的合成。这种差异至少部分归因于异羟肟酸酯快速代谢为相应的羧酸，而该羧酸对酶无活性。对影响这种代谢的结构特征的研究表明，2-芳基丙氧基异羟肟酸相对抗代谢水解。

  DOI：

  10.1021/jm00394a032
• 作为产物：
  描述：

  布洛芬 在 正丁基锂 、 氯化亚砜 、 苄基三甲基氢氧化铵 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 为溶剂， 反应 10.5h， 生成 2-(4-异丁基苯基)-2-甲基丙酸
  参考文献：
  名称：

  Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase-activating protein (FLAP)

  摘要：

  Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand-and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 mu M) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 mu M in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.048

文献信息

• Intermolecular Amination of Unactivated C(sp³ )−H Bonds with Cyclic Alkylamines: Formation of C(sp³ )−N Bonds through Copper/Oxygen-Mediated C(sp³ )−H/N−H Activation
  作者：Quan Gou、Yu-Wen Yang、Zi-Ning Liu、Jun Qin

  DOI：10.1002/chem.201603370

  日期：2016.11.2

  unactivated C(sp3)−H bonds by cyclic alkylamines mediated by Cu(OAc)2/O2 is reported. This method avoids the use of benzoyloxyamines as the aminating reagent, which are normally prepared from alkylamines in extra steps. A variety of unnatural β2, 2‐amino acid analogues are synthesized by this simple and efficient procedure. This approach offers a solution to the previous unmet challenge of C(sp3)−H/N−H

  报道了由Cu（OAc）2 / O 2介导的环状烷基胺对未活化的C（sp 3）-H键进行分子间胺化的第一个例子。该方法避免了使用苯甲酰氧基胺作为胺化试剂，该苯甲酰氧基胺通常是在额外的步骤中由烷基胺制备的。多种非天然β的2，2 -氨基酸类似物是通过这种简单且有效的方法进行合成。这种方法为C（sp 3）-H / N-H活化形成C（sp 3）-N键的先前未解决的挑战提供了解决方案。
• Synthesis and Pharmacological Evaluation of New Chemical Entities from Ibuprofen as Novel Analgesic Candidates
  作者：A. Ahmadi、N. Naderi、M. Daniali、S. Kazemi、S. Aazami、N. Alizadeh、B. Nahri-Niknafs

  DOI：10.1055/s-0034-1376976

  日期：——

  choice of drugs that are normally used for the treatment of pain and inflammation. Ibuprofen (I) and its analogues as the most widely used NSAIDs have been synthesized in recent years. In an effort to establish new candidates with improved analgesic properties, derivatives (II-VII) with substituted aromatic as well as aliphatic moieties were synthesized in this experiment and evaluated in formalin test

  非甾体类抗炎药（NSAIDs）是通常用于治疗疼痛和炎症的药物的首选。近年来，已经合成了布洛芬（I）及其类似物作为最广泛使用的非甾体抗炎药。为了建立具有改善镇痛作用的新候选药物，在该实验中合成了具有取代的芳香族以及脂肪族部分的衍生物（II-VII），并在大鼠的福尔马林试验中进行了评估。将结果与布洛芬和对照组进行比较。研究结果表明，相对于对照组和布洛芬基团，具有新的烷基苯环（VI和VII）的衍生物分别具有相似或更多的镇痛活性。可以证明在I中更多的烷基和苯基而不是对异丁基苯基部分是合理的。
• Exploring the fatty acid amide hydrolase and cyclooxygenase inhibitory properties of novel amide derivatives of ibuprofen
  作者：Alessandro Deplano、Jessica Karlsson、Mona Svensson、Federica Moraca、Bruno Catalanotti、Christopher J. Fowler、Valentina Onnis

  DOI：10.1080/14756366.2020.1743283

  日期：2020.1.1

  yl)propanamide (Ibu-AM68) was found to inhibit the hydrolysis of [3H]anandamide by rat brain homogenates by a reversible, mixed-type mechanism of inhibition with a Ki value of 0.26 µM and an α value of 4.9. At a concentration of 10 µM, the compound did not inhibit the cyclooxygenation of arachidonic acid by either ovine COX-1 or human recombinant COX-2. However, this concentration of Ibu-AM68 greatly

  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。
• METHOD AND APPARATUS FOR CONTINUOUS FLOW SYNTHESIS OF IBUPROFEN
  申请人：McQuade D. Tyler

  公开号：US20110054208A1

  公开（公告）日：2011-03-03

  A multi-step method for the continuous synthesis of ibuprofen or a synthetic precursor of ibuprofen is provided that does not require any intermediate purification or isolation steps and uses reagents compatible with downstream reactions. According to some embodiments, a method is provided wherein isobutylbenzene and a propionyl compound may be converted into a first product in a first Friedel Crafts acylation reaction. The first product may then be converted into a second product in a 1,2-aryl migration reaction. Finally, the second product may be converted into ibuprofen in a hydrolysis reaction. The present invention also provides a method wherein only the first and second reaction steps or only the second and third reaction steps are performed. An apparatus is also provided having two or more microreactors and two or more junctions in particular arrangements for the synthesis of ibuprofen or a synthetic precursor of ibuprofen.

  提供了一种多步法连续合成布洛芬或布洛芬的合成前体的方法，该方法不需要任何中间纯化或隔离步骤，并使用与下游反应兼容的试剂。根据某些实施例，提供了一种方法，其中异丁基苯和丙酰化合物可以在第一Friedel-Crafts酰化反应中转化为第一产物。然后，第一产物可以在1,2-芳基迁移反应中转化为第二产物。最后，第二产物可以在水解反应中转化为布洛芬。本发明还提供了一种仅执行第一和第二反应步骤或仅执行第二和第三反应步骤的方法。还提供了一种具有两个或多个微反应器和两个或多个特定排列的连接点的装置，用于合成布洛芬或布洛芬的合成前体。
• Method and composition for treating neurodegenerative disorders
  申请人：Hobden Adrian

  公开号：US20050288375A1

  公开（公告）日：2005-12-29

  The invention provides compositions and methods for treating neurodegenerative disorders. A method of the invention involves administering to an individual in need of treatment a composition having an R-NSAID and an NMDA antagonist. Another method of the invention involves administering to an individual in need of treatment a composition having at least two compounds that are capable of interacting with CYP2C9, wherein at least one of said compounds is an Aβ 42 lowering agent. The methods and compositions of the invention are useful for treating and preventing neurodegenerative disorders like Alzheimer's disease, dementia, mild cognitive impairment.

  本发明提供了用于治疗神经退行性疾病的组合物和方法。该发明的一种方法涉及向需要治疗的个体施用具有R-NSAID和NMDA拮抗剂的组合物。该发明的另一种方法涉及向需要治疗的个体施用至少两种能够与CYP2C9相互作用的化合物的组合物，其中至少一种化合物是Aβ42降低剂。该发明的方法和组合物对于治疗和预防像阿尔茨海默病、痴呆症、轻度认知障碍等神经退行性疾病非常有用。