(6S)-3,3,6-三甲基-2,5-哌嗪二酮 | 98735-75-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (6S)-3,3,6-三甲基-2,5-哌嗪二酮
• 英文名称: ciBA-L-Ala>
• 英文别名: (6S)-3,3,6-trimethylpiperazine-2,5-dione
• CAS: 98735-75-2
• 化学式: C₇H₁₂N₂O₂
• 分子量: 156.184
• InChiKey: QWLLBIAYORQXSC-BYPYZUCNSA-N

物化性质

• 沸点：
  418.9±38.0 °C(Predicted)
• 密度：
  1.041±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-tert-butoxycarbonyl-α-aminoisobutyryl-S-alanine methyl ester 以 甲苯 、 仲丁醇 为溶剂， 反应 4.0h， 生成 (6S)-3,3,6-三甲基-2,5-哌嗪二酮
  参考文献：
  名称：

  Stereochemistry of cyclic dipeptides. Assignment of the prochiral methylenes of 1-aminocyclopropane-1-carboxylic acid

  摘要：

  DOI：

  10.1021/jo00224a028

文献信息

• Investigation of Permeation of Theophylline through Skin Using Selected Piperazine-2,5-Diones
  作者：Aneta Pokorna、Pavel Bobal、Michal Oravec、Lucie Rarova、Janette Bobalova、Josef Jampilek

  DOI：10.3390/molecules24030566

  日期：——

  Transdermal administration of drugs that penetrate, in this case directly into the blood circulation, has many advantages and is promising for many drugs thanks to its easy application and good patient compliance. (S)-8-Methyl-6,9-diazaspiro[4.5]decan-7,10-dione (alaptide), has been studied as a potential chemical permeation enhancer. Based on its structure, four selected piperazine-2,5-diones were synthesized by means of multi-step synthetic pathways. All the compounds were investigated on their ability to enhance the permeation of the model drug theophylline from the hydrophilic medium propylene glycol:water (1:1). In vitro experiments were performed using vertical Franz diffusion cells at constant temperature 34 ± 0.5 °C and using full-thickness pig (Sus scrofa f. domestica) ear skin. Withdrawn samples were analyzed by RP-HPLC for determination of the permeated amount of theophylline. All the compounds were applied in ratio 1:10 (w/w) relative to the amount of theophylline. One hour after application, the permeated amount of theophylline from formulations with alaptide and (3S,6S)-3,6-dimethylpiperazine-2,5-dione, was ca. 15- and 12-fold higher, respectively, than from the formulation without the tested compounds. Despite the enhancement ratio of both enhancers in a steady state was ca. 2.3, the pseudo-enhancement ratio in the time range from 1 to 3 h was 4.4. These enhancement ratios indicate that the compounds are able to enhance the permeation of agents through the skin; however, the short-term application of both compound formulations seems to be more advantageous. In addition, the screening of the cytotoxicity of all the prepared compounds was performed using three cell lines, and the compounds did not show any significant toxic effect.

  药物经皮给药，直接穿透进入血液循环，在许多药物中具有许多优点，并且由于其易于应用和患者良好的依从性，对许多药物来说是很有前景的。 (S)-8-甲基-6,9-二氮杂螺[4.5]癸烷-7,10-二酮（alaptide）已被研究作为潜在的化学渗透增强剂。基于其结构，通过多步合成途径合成了四种选择的哌嗪-2,5-二酮。所有化合物均在亲水性介质丙二醇：水（1：1）中增强模型药物茶碱的渗透能力。在恒定温度34±0.5°C下，使用垂直Franz扩散池进行体外实验，并使用全厚度猪（Sus scrofa f. domestica）耳皮肤。通过RP-HPLC分析提取的样品，以确定茶碱的渗透量。所有化合物均按照与茶碱量的比例1：10（w/w）应用。在应用后一小时，含有alaptide和（3S,6S）-3,6-二甲基哌嗪-2,5-二酮的配方中，茶碱的渗透量分别比不含被测试化合物的配方高约15倍和12倍。尽管两种增强剂在稳态下的增强比约为2.3，但在1至3小时的时间范围内的伪增强比为4.4。这些增强比表明这些化合物能够增强药物通过皮肤的渗透；然而，两种化合物配方的短期应用似乎更有优势。此外，使用三种细胞系对所有制备的化合物的细胞毒性进行了筛查，这些化合物没有显示出任何显著的毒性作用。