ketoprofen hydroxyethyl ester | 70125-82-5

• 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: ketoprofen hydroxyethyl ester
• 英文别名: 2-(3-benzoylphenyl)propionic acid 2-hydroxyethyl ester；rac Ketoprofen PEG 400 Ester；2-hydroxyethyl 2-(3-benzoylphenyl)propanoate
• CAS: 70125-82-5
• 化学式: C₁₈H₁₈O₄
• 分子量: 298.339
• InChiKey: DPWFGFQKRVVHHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ketoprofen hydroxyethyl ester 以 phosphate buffer 为溶剂， 生成 酮基布洛芬
  参考文献：
  名称：

  In vitro evaluation of acyloxyalkyl esters as dermal prodrugs of ketoprofen and naproxen

  摘要：

  A series of acyloxyalkyl esters of ketoproien and naproxen were synthesized and investigated as topical prodrugs with the aim of improving the dermal delivery of the drugs. In addition, some hydroxyalkyl esters of ketoprofen and naproxen were synthesized as possible intermediates of acyloxyalkyl prodrugs. All of the prodrugs were more lipophilic than their parent molecules, as evaluated by drug partitioning between l-octanol and phosphate buffer at pH 7.4 (log P-app). However, their solubilities in aqueous solutions decreased markedly compared with the parent molecules. The prodrugs were stable toward chemical hydrolysis in aqueous solutions (pH 7.4), but were hydrolyzed to the parent drug both in 80% human serum and in human skin homogenate, with half-lives ranging from 4 to 137 min and from 13 to 403 min, respectively. The abilities of the selected naproxen acyloxyalkyl prodrugs to deliver naproxen through excised human skin were evaluated. Generally, the prodrugs showed similar dermal delivery as the parent drug through cadaver skin. In the present series of lipophilic prodrugs of naproxen, the prodrug with the highest aqueous solubility was the most effective prodrug to deliver naproxen through the skin.

  DOI：

  10.1021/js970465w
• 作为产物：
  描述：

  酮基布洛芬 、 2-溴乙醇 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到ketoprofen hydroxyethyl ester
  参考文献：
  名称：

  大型中性氨基酸转运蛋白可通过前药输送脑部药物。

  摘要：

  血脑屏障有效地控制了药物分子进入大脑。我们描述了一种可行的方法，可通过将模型化合物与L-酪氨酸缀合，通过特定的大型中性氨基酸转运蛋白（LAT1）实现载体介导的药物转运到大鼠脑内。选择不是LAT1底物的亲水性药物酮洛芬作为模型化合物。用原位大鼠脑灌注技术确定前药对大脑的吸收机理和动力学。发现前药的脑摄取是浓度依赖性的。此外，特定的LAT1抑制剂可显着降低前药对大脑的吸收。因此，我们的结果首次揭示了药物-底物偶联物能够通过LAT1将药物转运到大脑中。

  DOI：

  10.1021/jm701175d

文献信息

• [EN] LONG-ACTING KETOPROFEN COMPOSITIONS<br/>[FR] COMPOSITIONS DE KÉTOPROFÈNE À ACTION PROLONGÉE
  申请人：ZOETIS LLC

  公开号：WO2015095045A1

  公开（公告）日：2015-06-25

  The invention describes a long-acting veterinary composition comprising at least one ketoprofen ester prodrug. The composition also comprises at least one veterinary acceptable triglyceride, and optionally, at least one preservative, and optionally, at least one additional veterinary acceptable excipient. The invention also describes a method of treating an animal for fever, pain, and/or inflammation by administering the long-acting composition comprising at least one ketoprofen ester prodrug to the animal in need thereof.

  该发明描述了一种长效兽医组合物，其中包括至少一种酮洛芬酯前药。该组合物还包括至少一种兽医可接受的甘油三酯，可选地，至少一种防腐剂，以及可选地，至少一种其他兽医可接受的赋形剂。该发明还描述了一种通过向需要治疗发热、疼痛和/或炎症的动物投与至少一种酮洛芬酯前药的长效组合物来治疗动物的方法。
• LONG-ACTING KETOPROFEN COMPOSITIONS
  申请人：ZOETIS SERVICES LLC

  公开号：US20160303065A1

  公开（公告）日：2016-10-20

  The invention describes a long-acting veterinary composition comprising at least one ketoprofen ester prodrug. The composition also comprises at least one veterinary acceptable triglyceride, and optionally, at least one preservative, and optionally, at least one additional veterinary acceptable excipient. The invention also describes a method of treating an animal for fever, pain, and/or inflammation by administering the long-acting composition comprising at least one ketoprofen ester prodrug to the animal in need thereof.