acyclovir hexanoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: acyclovir hexanoate
• 英文别名: 2-amino-9-[(2-hexanoyloxy)ethyl-oxy-methyl]-1,9-dihydro-6H-purin-6-one；Acyclovircaprylester；2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethyl hexanoate
• 化学式: C₁₄H₂₁N₅O₄
• 分子量: 323.352
• InChiKey: SLVUVSMVSSTFHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  阿昔洛韦 生成 acyclovir hexanoate
  参考文献：
  名称：

  SCHAEFFER, H. J.

  摘要：

  DOI：

文献信息

• New Green Synthesis and Formulations of Acyclovir Prodrugs
  作者：Rubén de Regil-Hernández、Fernando Martínez-Lagos、Amalia Rodríguez-Bayón、José-Vicente Sinisterra

  DOI：10.1248/cpb.59.1089

  日期：——

  Different green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is described. Hexanoic, decanoic, dodecanoic and tetradecanoic acyclovir esters were synthesized reacting acyclovir and the respective acid anhydride in dimethyl sulfoxide (DMSO), in solvents from renewable sources and without solvent (T=30°C). Yields in prodrugs after 10 min of reaction were >95% using DMSO as solvent. The purification methodology was very simple, shorter and greener than previously described. The biosolvent, N,N-dimethylamide of decanoic acid, let us to obtain >95% yield at 24 h. This oily biosolvent is not dermotoxic and the reaction crude can directly be used in topic formulations. Syntheses without solvent proceeded successfully for acyclovir esters. Indeed, dodecanoate and tetradecanoate yielding >98% conversion of reactants in 30 min. In spite of requiring mild temperature (65°C), substrate molar ratios were lowered to 1 : 1, thus conducing to a more efficient use of raw materials. The synthetic procedures were scaled up to a 300 g batch (yield 98—99% isolated ester). These esters can be used as acyclovir prodrugs in topic formulations. The esters release from an oil/water micro-emulsion and a hydrogel formulation were tested with good results.

  本文介绍了阿昔洛韦烷基酯（阿昔洛韦原药）的不同绿色合成方法。阿昔洛韦和相应的酸酐在二甲基亚砜（DMSO）、可再生资源溶剂和无溶剂（T=30°C）中反应合成了己酸、癸酸、十二酸酐和十四酸酐阿昔洛韦酯。使用二甲基亚砜作为溶剂，反应 10 分钟后原药的产率大于 95%。与之前描述的方法相比，纯化方法非常简单、时间更短、更环保。使用癸酸的 N,N-二甲基酰胺作为生物溶剂，24 小时后的产率>95%。无溶剂合成阿昔洛韦酯类也取得了成功。事实上，十二酸酯和十四酸酯在 30 分钟内的反应物转化率大于 98%。尽管需要温和的温度（65°C），但底物摩尔比降低到了 1:1，从而更有效地利用了原材料。合成程序已扩大到 300 克的批量（分离酯的产量为 98-99%）。这些酯类可作为阿昔洛韦原药用于主题制剂中。经测试，这些酯类从油/水微乳剂和水凝胶配方中释放的效果良好。
• ——
  作者：Hiroto Bando、Toshihide Takagi、Fumiyoshi Yamashita、Yoshinobu Takakura、Mitsuru Hashida

  DOI：10.1023/a:1016000827719

  日期：——

  Purpose. A theoretical design of percutaneous penetration enhancement in which prodrug derivation and enhancer application are combined is proposed based on the skin diffusion model and it is experimentally verified.Methods. Employing acyclovir as a model drug, the hypothesis was tested by synthesis of its prodrugs and evaluation of their in vitro permeation in the rat skin, with or without a penetration enhancer, 1-geranylazacycloheptan-2-one(GACH).Results. Among five acyclovir prodrugs, those with higher lipophilicities (propionate, butyrate, valerate, and hexanoate prodrugs) showed greater skin penetration than those of hydrophilic prodrugs (acetate), when administered in combination with GACH. Furthermore, the observed enhancement ratios were in good agreement with those predicted by theoretical consideration.Conclusions. Thus, skin permeation of prodrugs applied with an enhancer can be predicted and optimized by model analysis.
• Process for the manufacture of acyclovir pro-drugs
  申请人：Cognis IP Management GmbH

  公开号：EP2184286B1

  公开（公告）日：2012-02-29
• SCHAEFFER, H. J.
  作者：SCHAEFFER, H. J.

  DOI：——

  日期：——