naproxen hydroxybutyl ester | 214708-55-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: naproxen hydroxybutyl ester
• 英文别名: 4-Hydroxybutyl 2-(6-methoxynaphthalen-2-yl)propanoate
• CAS: 214708-55-1
• 化学式: C₁₈H₂₂O₄
• 分子量: 302.37
• InChiKey: GLRAPXSHDPTPHO-UHFFFAOYSA-N

物化性质

• 沸点：
  460.8±30.0 °C(Predicted)
• 密度：
  1.142±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 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 hydroxybutyl 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21%的产率得到naproxen hydroxybutyl 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

• [EN] PROCESS FOR THE PREPARATION OF NITRATE ACID ESTER OF ORGANIC COMPOUNDS<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'ESTER D'ACIDE DE NITRATE DE COMPOSÉS ORGANIQUES
  申请人：NICOX SA

  公开号：WO2012152438A1

  公开（公告）日：2012-11-15

  The present invention relates to a one-step process for the synthesis of nitric acid esters or 15N isotopically labeled nitrate esters of organic compounds starting from the correspondent alcohols. Formula (I).

  这项发明涉及一种从相应的醇出发，通过一步法合成有机化合物的硝酸酯或15N同位素标记的硝酸酯的过程。公式（I）。
• Synthesis and in Vitro Evaluation of Novel Morpholinyl- and Methylpiperazinylacyloxyalkyl Prodrugs of 2-(6-Methoxy-2-naphthyl)propionic Acid (Naproxen) for Topical Drug Delivery
  作者：Jarkko Rautio、Tapio Nevalainen、Hannu Taipale、Jouko Vepsäläinen、Jukka Gynther、Krista Laine、Tomi Järvinen

  DOI：10.1021/jm991149s

  日期：2000.4.1

  (3a,b) and methylpiperazinylacyloxyalkyl (3c-f) esters of 2-(6-methoxy-2-naphthyl)propionic acid were synthesized and evaluated in vitro for topical drug delivery as potential prodrugs of naproxen (1). Compounds 3a-f were prepared by coupling the corresponding naproxen hydroxyalkyl ester with the morpholinyl- or (4-methyl-1-piperazinyl)acyl acid in the presence of dicyclohexylcarbodiimide (DCC) and 4

  合成了2-（6-甲氧基-2-萘基）丙酸的各种新型吗啉基-（3a，b）和甲基哌嗪基甲酰氧基烷基（3c-f）酯，并在体外评估了其作为萘普生的潜在前药的局部药物递送。通过在二环己基碳二亚胺（DCC）和4-（二甲基氨基）吡啶（DMAP）存在下，将相应的萘普生羟烷基酯与吗啉基-或（4-甲基-1-哌嗪基）酰基偶联，制备化合物3a-f，并进行定量水解（t（1/2）= 1-26分钟）至人血清中的萘普生。与萘普生相比，化合物3c-f在pH 5.0时显示出较高的水溶性和相似的亲脂性，这取决于它们的辛醇-缓冲液分配系数（log P（app））。在pH 7.4时，它们的亲脂性明显高于萘普生。最好的前药3c导致4和1。与萘普生在pH 7.4和5.0下相比，皮肤渗透分别提高了5倍。本研究表明，使用甲基哌嗪基可产生在中性和弱酸性条件下部分未电离的前药，因此，就水溶性和亲脂性而言，可实现理想的组合。此外，所得的两相溶解性
• [EN] NAPROXCINOD PROCESS AND SOLID DISPERSION<br/>[FR] PROCÉDÉ DE FABRICATION DE NAPROXCINOD ET DISPERSION SOLIDE DE NAPROXCINOD
  申请人：REDDYS LAB LTD DR

  公开号：WO2009149053A2

  公开（公告）日：2009-12-10

  Processes for the preparation of naproxcinod and its purification, solid dispersions of naproxcinod with a pharmaceutically acceptable carrier, and processes for making dispersions. Also provided is crystalline 2-(S)-(4-chlorobutyl)-2-(6-methoxy-2-naphthyl)-propanoate and methods for its preparation.

  本文提供了制备naproxcinod及其纯化的过程，naproxcinod与药用载体的固体分散以及制备分散的过程。还提供了结晶的2-(S)-(4-氯丁基)-2-(6-甲氧基-2-萘基)-丙酸酯及其制备方法。
• METHOD FOR PURIFYING 4-(NITROOXY)BUTYL(2S)-2-(6-METHOXY-2-NAPHTHYL) PROPANOATE
  申请人：Allegrini Pietro

  公开号：US20100256411A1

  公开（公告）日：2010-10-07

  The present invention relates to a method for purifying naproxcinod comprising the steps of: a) dissolving or dispersing a mixture containing naproxcinod in an amount higher than 90% by weight in a solvent; b) cooling the solution or two phases dispersion under stirring to a temperature ranging from −20° C. to 10° C. c) optionally seeding the solution with crystals of naproxcinod d) stirring, by maintaining the temperature in the range from −40° C. to 10° C. e) collecting the formed solid by maintaining the temperature under 15° C. A further object of the invention is a crystalline form of naproxcinod.

  本发明涉及一种纯化Naproxcinod的方法，包括以下步骤： a）在溶剂中溶解或分散含有90%以上Naproxcinod的混合物； b）在搅拌下将溶液或两相分散体冷却到-20℃至10℃的温度范围内； c）可选地将Naproxcinod的晶体作为种子加入溶液中； d）保持温度在-40℃至10℃的范围内搅拌； e）通过保持温度低于15℃来收集形成的固体。 本发明的另一个目的是提供Naproxcinod的晶体形式。
• Pyridone Directed Ru-Catalyzed Olefination of <i>sp</i>²(C–H) Bond Using Michael Acceptors: Creation of Drug Analogues
  作者：Smruti Ranjan Mohanty、Namrata Prusty、Tanmayee Nanda、Shyam Kumar Banjare、Ponneri C. Ravikumar

  DOI：10.1021/acs.joc.2c00428

  日期：2022.5.6