naproxen hydroxypropyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: naproxen hydroxypropyl ester
• 英文别名: 3-Hydroxypropyl 2-(6-methoxynaphthalen-2-yl)propanoate
• 化学式: C₁₇H₂₀O₄
• 分子量: 288.343
• InChiKey: IKMOTDIWFIROFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  naproxen hydroxypropyl ester 以 phosphate buffer 为溶剂， 生成 2-(6-甲氧基-2-萘基)丙酸
  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：

  naproxen sodium 、 alkaline earth salt of/the/ methylsulfuric acid 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以87%的产率得到naproxen hydroxypropyl ester
  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

文献信息

• US5866538A
  申请人：——

  公开号：US5866538A

  公开（公告）日：1999-02-02
• US5898028A
  申请人：——

  公开号：US5898028A

  公开（公告）日：1999-04-27
• US6043214A
  申请人：——

  公开号：US6043214A

  公开（公告）日：2000-03-28
• USRE41151E1
  申请人：——

  公开号：USRE41151E1

  公开（公告）日：2010-02-23
• [EN] NOVEL PRODRUGS OF NON-STEROIDAL ANTI-INFLAMMATORY CARBOXYLIC ACIDS, THEIR PREPARATION AND USE<br/>[FR] NOUVEAUX PROMEDICAMENTS A BASE D'ACIDES CARBOXYLIQUES ANTI-INFLAMMATOIRES NON STEROIDIQUES; PREPARATION ET UTILISATION
  申请人：JAERVINEN TOMI

  公开号：WO2000023419A1

  公开（公告）日：2000-04-27

  The present invention concerns novel aminoacyloxyalkyl prodrugs of non-steroidal anti-inflammatory carboxylic acids of formula R-COO-R1-O-R2 wherein R-COO- represents the acyloxy residue of a non-steroidal anti-inflammatory carboxylic acid, R1 is a saturated or unsaturated, a straight-chain, branched or cyclic alkylene or alkylidene group of 1 to 8 carbon atoms, which can optionally be substituted, and R2 is the aminoacyl residue of a synthetic or natural amino acid, or a secondary, tertiary or quaternary aminoacyl group, as well as the nontoxic pharmaceutically acceptable acid addition salts thereof, methods for preparing the said prodrug forms, pharmaceutical compositions containing such prodrug forms, and methods for using the prodrug forms.