ibuprofen eugenol ester | 872726-16-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ibuprofen eugenol ester
• 英文别名: (2-methoxy-4-prop-2-enylphenyl) 2-[4-(2-methylpropyl)phenyl]propanoate
• CAS: 872726-16-4
• 化学式: C₂₃H₂₈O₃
• 分子量: 352.474
• InChiKey: UCBNCRLXJCEERQ-UHFFFAOYSA-N

物化性质

• 沸点：
  454.9±45.0 °C(Predicted)
• 密度：
  1.037±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 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：

  ibuprofen eugenol ester 在 rat plasma 水 作用下， 以 甲醇 、 phosphate buffer 为溶剂， 生成 丁香酚 、 布洛芬
  参考文献：
  名称：

  Zhao; Chen; Gao, Pharmazie, 2005, vol. 60, # 12, p. 883 - 887

  摘要：

  DOI：
• 作为产物：
  描述：

  丁香酚 、 布洛芬 在 二甲基亚砜 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 ibuprofen eugenol ester
  参考文献：
  名称：

  Synthesis of Ibuprofen Eugenol Ester and Its Microemulsion Formulation for Parenteral Delivery

  摘要：

  本研究的目的是探讨利用基于磷脂的微乳液系统肠外给药水溶性差的亲脂性药物的可能性。布洛芬丁香酚酯（IEE）是一种高亲脂性化合物，由布洛芬和丁香酚合成，并分离出无定形白色固体，熔点为 40.2±0.1 °C，其结构由红外光谱、1H-NMR 和 MS 光谱证实。介绍了一种药用微乳液体系，该体系以 Miglyol 812、大豆磷脂酰胆碱（SbPC）和聚（乙二醇）（660）-12-羟基硬脂酸酯（Solutol® HS-15）以及 PEG400 和乙醇分别作为油相、表面活性剂和辅助表面活性剂，并从稳定性、液滴粒度分布（DSD）及其对 IEE 的增溶能力方面对其进行了表征。在由 6.4% 的布洛芬丁香酚、9.6% 的 Miglyol 812、6% 的 SbPC、6% 的 HS-15、8.4% 的 PEG400、3.6% 的乙醇和 60% 的蒸馏水（重量比）组成的优化微乳剂配方中，IEE 的溶解度比在水中高出约 21000 倍。测定了静脉注射微乳剂后布洛芬的血药浓度，并与布洛芬溶液的血药浓度进行了比较。结果表明，该微乳剂系统可能是一种很有前途的水溶性差的亲脂性药物静脉注射剂型。

  DOI：

  10.1248/cpb.53.1246

文献信息

• Aryl (Ethanoic) Propanoic Acid Ascorbyl Ester, Preparation Method Thereof And Medicament Containing The Same
  申请人：Tang Luhong

  公开号：US20120115897A1

  公开（公告）日：2012-05-10

  The present invention designs and synthesizes the ascorbyl ester derivatives of the aryl (ethanoic) propanoic acid non-steroidal anti-inflammatory medicaments, such as ibuprofen, ketoprofen and naproxen, and addition salt of the derivatives with pharmaceutical acid or pharmaceutical alkaline. The non-steroidal anti-inflammatory medicament which takes the ibuprofen as the representative is a common antipyretic analgesic medicament. The invention has remarkable antipyretic and analgesic effects and good safety except for anti-inflammatory effect, thus being not only suitable for adults, but also suitable for the elderly people, infants and children. The aryl (ethanoic) propanoic acid ascorbyl ester can be converted into ascorbyl ester derivatives and the addition salts of the derivatives with pharmaceutical acid or pharmaceutical alkaline, which can improve the water solubility thereof, facilitate intravenously administration, reduce the onset time, improve the bioavailability, reduce the stimulation effect to gastrointestinal tract, and enhance the penetrating capacity to hemato encephalic barrier, and can be used as a novel medicament to be applied for antiphlogistic, antipyresis, analgesia, treatment of arthritis, dysmenorrheal, multiple sclerosis, pneumonia cystic fibrosis and patent ductus arteriosus of premature infants, and prevention and treatment of cerebral apoplexy, hypoxic-ischemic brain damage, senile dementia and certain cancers.

  本发明设计并合成了芳基（乙酸）丙酸非甾体抗炎药物，例如布洛芬、酮洛芬和萘普生的抗坏血酸酯衍生物，以及这些衍生物与药用酸或药用碱的加成盐。以布洛芬为代表的非甾体抗炎药是一种常见的解热镇痛药。本发明除了具有抗炎效果外，还具有显著的解热和镇痛效果，安全性良好，因此不仅适用于成人，也适用于老年人、婴幼儿。芳基（乙酸）丙酸抗坏血酸酯可转化为抗坏血酸酯衍生物以及这些衍生物与药用酸或药用碱的加成盐，这可以提高其水溶性，便于静脉给药，减少起效时间，提高生物利用度，减少对胃肠道的刺激作用，增强穿透血脑屏障的能力，并可作为新型药物应用于消炎、解热、镇痛、治疗关节炎、痛经、多发性硬化症、肺炎、囊性纤维化和早产儿动脉导管未闭，以及预防和治疗脑卒中、缺氧缺血性脑损伤、老年痴呆症和某些癌症。
• IBUPROFEN-BASED COMPOUND, PREPARATION METHOD, USE, AND FORMULATION OF THE SAME
  申请人：Su Qing

  公开号：US20140112978A1

  公开（公告）日：2014-04-24

  Disclosed are compounds based on ibuprofen, their preparation methods, uses and pharmaceutical preparation. The compounds have structures shown as formula (1), wherein, m, n are integers and fulfill the requirements of 0≦n≦6, 0≦m≦6, respectively. The preparation methods for the compounds based on ibuprofen are as follows: contacting and reacting 2-(4-isobutyl-phenyl) propionic acid to have contact reaction with a solution of an organic acid ester in the presence of a catalyst under substitution reaction conditions The present compounds can be used to prepare nonsteroidal anti-inflammatory drugs. The preparation can be preparation of fat emulsion, liposome, and dried emulsion and so on.

  揭示了基于布洛芬的化合物，它们的制备方法，用途和药物制备。这些化合物的结构如公式（1）所示，其中m，n为整数，满足0≦n≦6，0≦m≦6的要求。基于布洛芬的化合物的制备方法如下：将2-(4-异丁基苯基)丙酸与有机酸酯溶液在催化剂存在下进行接触反应，以取代反应条件。这些化合物可用于制备非甾体抗炎药。制备可以是脂肪乳剂、脂质体、干燥乳剂等。
• Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and eugenol
  作者：Vivekkumar K. Redasani、Sanjay B. Bari

  DOI：10.1016/j.ejmech.2012.08.030

  日期：2012.10

  traditional medicinal values. Prodrugs are found to be highly lipophilic as compared to parent drug. All the prodrugs are found to be highly stable at acidic pH while undergoes hydrolysis at neutral and alkaline pH as indicated by their t1/2 values. Synthesized prodrugs derivatives show increased anti-inflammatory activity that might be attributed to synergistic effect as ibuprofen conjugates to natural analgesics

  本工作涉及通过化学掩蔽羧基来延缓胃肠道副作用从而提高外消旋布洛芬疗效的简单有效的方法。这是通过布洛芬酯衍生物与天然存在的酚类和醇类化合物作为互用前体药物进行合成和评估而实现的。薄荷醇等促销品；选择百里香酚和丁香酚是为了获得协同作用，因为它们是具有传统药用价值的天然镇痛药。与母体药物相比，发现前药具有高度亲脂性。如t 1/2所示，发现所有前药在酸性pH下均高度稳定，而在中性和碱性pH下均经历水解。价值观。合成的前药衍生物显示出增强的抗炎活性，这可能归因于布洛芬偶联物与天然镇痛药的协同作用。与布洛芬相比，溃疡指数显示出胃溃疡的减少很多，从而成功掩盖了酸性组。
• ASCORBIC ACID ARYL ACETATE/PROPIONATE ESTER, PREPARATION METHOD AND PHARMACEUTICAL COMPOSITION THEREOF
  申请人：Wuxi Hongrui Biomedical Technology Co., Ltd.

  公开号：EP2431361A1

  公开（公告）日：2012-03-21

  The present invention designs and synthesizes ascorbyl ester derivatives of aryl (ethanoic) propanoic acid non-steroidal anti-inflammatory medicaments, such as ibuprofen, ketoprofen and naproxen, and addition salt of the derivatives with pharmaceutical acid or pharmaceutical alkali. The non-steroidal anti-inflammatory medicament which takes the ibuprofen as the representative is a common antipyretic analgesic medicament. The invention has remarkable antipyretic and analgesic effects and good safety except for anti-inflammatory effect, thus being not only suitable for adults, but also suitable for elderly people, infants and children. The aryl (ethanoic) propanoic acid ascorbyl ester can be converted into ascorbyl ester derivatives and the addition salts of the derivatives with pharmaceutical acid or pharmaceutical alkali, which can improve the water solubility thereof, facilitate intravenously administration, reduce the onset time, improve the bioavailability, reduce the stimulation effect to gastrointestinal tract, and enhance the penetrating capacity to hemato encephalic barrier, and can be used as a novel medicament to be applied for antiphlogistic, antipyresis, analgesia, treatment of arthritis, dysmenorrheal, multiple sclerosis, pneumonia cystic fibrosis and patent ductus arteriosus of premature infants, and prevention and treatment of cerebral apoplexy, hypoxic-ischemic brain damage, senile dementia and certain cancers.

  本发明设计合成了布洛芬、酮洛芬、萘普生等芳基（乙）丙酸类非甾体抗炎药物的抗坏血酸酯衍生物，以及衍生物与药用酸或药用碱的加成盐。以布洛芬为代表的非甾体抗炎药物是一种常用的解热镇痛药物。本发明除消炎作用外，解热镇痛效果显著，安全性好，不仅适用于成人，也适用于老人、婴幼儿。芳基（乙）丙酸抗坏血酸酯可转化为抗坏血酸酯衍生物及衍生物与药用酸或药用碱的加成盐，可提高其水溶性，便于静脉给药，缩短起效时间，提高生物利用度，减少对胃肠道的刺激作用、可作为新型药物应用于抗抑郁、镇痛、治疗关节炎、痛经、多发性硬化、肺炎囊性纤维化和早产儿动脉导管未闭，以及预防和治疗脑中风、缺氧缺血性脑损伤、老年性痴呆和某些癌症。
• PHILLYGENIN IBUPROFEN ESTER, PREPARATION METHOD THEREFOR, AND APPLICATIONS THEREOF
  申请人：Fu, Li

  公开号：EP3178822B1

  公开（公告）日：2019-03-13