2-hydroxyethyl 2-(6-methoxy-2-naphthyl)propanoate | 110599-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-hydroxyethyl 2-(6-methoxy-2-naphthyl)propanoate
• 英文别名: naproxen hydroxyethyl ester；6-Methoxy-alpha-methyl-2-naphthaleneacetic acid 2-hydroxyethyl ester；2-hydroxyethyl 2-(6-methoxynaphthalen-2-yl)propanoate
• CAS: 110599-10-5
• 化学式: C₁₆H₁₈O₄
• 分子量: 274.317
• InChiKey: NYYKRAQUHNVACN-UHFFFAOYSA-N

物化性质

• 沸点：
  452.3±25.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 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：

  2-hydroxyethyl 2-(6-methoxy-2-naphthyl)propanoate 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96%的产率得到2-hydroxyethyl 2-(6-methoxy-2-naphthyl)propanoate
  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

• 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
• Optically active alpha-substituted aryl ketones, their preparation and their use in preparing alpha-arylalkanoic acids
  申请人：SYNTEX PHARMACEUTICALS INTERNATIONAL LIMITED

  公开号：EP0081993A2

  公开（公告）日：1983-06-22

  Pharmaceutically useful optically active a-arylalkanoic acids of the formula where Ar is aryl and R1 is alkyl or cycloalkyl or esters,ortho esters, or amides thereof are stereoselectively prepared by contacting a reagent of the formula Ar-MX, (Ar) 2M or ArM' where M is Cd, Cu(II), Mn(II), Mg or Zn, and M' is Cu(I) or Li, and X is halogen, with an optically active compound of the formula where Z is a leaving group and Y is halogen, acyloxy or where R' and R" are alkyl, aryl or with N are a heterocyclic group, to form the optically active ketone of the formula which is ketalized and rearranged to said acid, ester, ortho ester or amide. Alternatively, said ketone is reduced to the corresponding alkanol, which is rearranged to the a-arylalkanal. The alkanal so produced is converted to said acid by conventional methods.

  式中 Ar 为芳基，R1 为烷基或环烷基的具有光学活性的 a-芳基烷酸或其酯、正酯或酰胺，可通过与式中的试剂 其中 Ar 为芳基，R1 为烷基或环烷基或其酯、正交酯或酰胺，通过将式 Ar-MX、(Ar) 2M 或 ArM'（其中 M 为 Cd、Cu(II)、Mn(II)、Mg 或 Zn，M'为 Cu(I) 或 Li，X 为卤素）的试剂与式中的光学活性化合物接触，立体选择性地制备。 其中 Z 是离去基团，Y 是卤素、酰氧基或 其中 R'和 R "为烷基、芳基或与 N 一起为杂环基团，形成式中的光学活性酮。 经酮化后重新排列为所述的酸、酯、正交酯或酰胺。或者，将所述酮还原为相应的烷醇，再重新排列为 a-芳基烷醛。生成的烷醛通过常规方法转化为所述的酸。
• US4605758A
  申请人：——

  公开号：US4605758A

  公开（公告）日：1986-08-12
• US4749804A
  申请人：——

  公开号：US4749804A

  公开（公告）日：1988-06-07
• US4912254A
  申请人：——

  公开号：US4912254A

  公开（公告）日：1990-03-27