5-[1,2]dithiolan-3-ylpentanoic acid 6-(5-[1,2]dithiolan-3-ylpentanoyloxy)hexyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二硫杂环戊烷
• 英文名称: 5-[1,2]dithiolan-3-ylpentanoic acid 6-(5-[1,2]dithiolan-3-ylpentanoyloxy)hexyl ester
• 英文别名: 6-[5-(Dithiolan-3-yl)pentanoyloxy]hexyl 5-(dithiolan-3-yl)pentanoate
• 化学式: C₂₂H₃₈O₄S₄
• 分子量: 494.805
• InChiKey: PQHYEVIUACPIRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  154
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Thioctic acid 在 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 5-[1,2]dithiolan-3-ylpentanoic acid 6-(5-[1,2]dithiolan-3-ylpentanoyloxy)hexyl ester
  参考文献：
  名称：

  Synthesis and characterization of new and potent α-lipoic acid derivatives

  摘要：

  alpha-Lipoic acid [5-[1,2]-dithiolan-3-yl-pentanoic acid (LA)] is a natural antioxidant and cofactor of several enzymes. It increases the glucose transport activity in skeletal muscles and adipocytes in a non-insulin dependent manner. Therefore, LA is widely used in Type 2 diabetic patients as an oral auxiliary drug. However, large doses of LA (0.8-1.8 gr/day po) are required due to its unfavorable pharmacokinetic parameters. In order to improve these parameters, we synthesized ester and amide LA derivates. Two of these newly synthesized compounds, 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]dithiolan-3yl-pentanoylamino)-propyl]-amide (AN-7) and 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]-dithiolan-3yl-pentanoyloxy)-propyl ester (AN-8) augmented the rate glucose transport in myotubes in culture in the absence or presence of insulin. Their potency was 12-fold higher than that of the parent compound; their maximal stimulatory effect was 1.5-fold higher than that of LA. When tested in vivo in streptozotocin-diabetic C57/Black mice, AN-7 (10 mg/kg/day for 2 weeks, sc) reduced blood glucose level by 39% while a higher dose of LA (50 mg/kg/day for 2 weeks, sc) lowered it by 30%. These results indicate that AN-7 is more potent than LA in augmenting glucose transport in skeletal muscles and reducing blood glucose in diabetic animals. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.11.025

文献信息

• Nanoparticles of lipoic acid esters: preparation and antioxidant effect
  作者：Vasiliy A. Shchelkonogov、Anna M. Inshakova、Alina V. Shipelova、Olga A. Baranova、Andrey V. Chekanov、Natalya S. Shastina、Ella Yu. Solov'eva、Anatoly I. Fedin

  DOI：10.1016/j.mencom.2021.07.023

  日期：2021.7

  Five lipoic acid esters were synthesized, and their nanoforms based on copolymer Pluronic F68 and phosphatidylcholine were obtained. The most pronounced antioxidant effect on neutrophils activated by phorbol-12-myristate-13-acetate was shown by the nanodispersion containing the derivative of lipoic acid with hexane-1,6-diol, reducing the concentration of reactive oxygen species by 7.5 times.

  合成了五种硫辛酸酯，并获得了基于共聚物 Pluronic F68 和磷脂酰胆碱的纳米形式。含有硫辛酸衍生物和 1,6-二醇的纳米分散体对 phorbol-12-myristate-13-acetate 活化的中性粒细胞具有最显着的抗氧化作用，可将活性氧浓度降低 7.5 倍。
• Synthesis and characterization of new and potent α-lipoic acid derivatives
  作者：Arie Gruzman、Adel Hidmi、Jehoshua Katzhendler、Abdalla Haj-Yehie、Shlomo Sasson

  DOI：10.1016/j.bmc.2003.11.025

  日期：2004.3

  alpha-Lipoic acid [5-[1,2]-dithiolan-3-yl-pentanoic acid (LA)] is a natural antioxidant and cofactor of several enzymes. It increases the glucose transport activity in skeletal muscles and adipocytes in a non-insulin dependent manner. Therefore, LA is widely used in Type 2 diabetic patients as an oral auxiliary drug. However, large doses of LA (0.8-1.8 gr/day po) are required due to its unfavorable pharmacokinetic parameters. In order to improve these parameters, we synthesized ester and amide LA derivates. Two of these newly synthesized compounds, 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]dithiolan-3yl-pentanoylamino)-propyl]-amide (AN-7) and 5-[1,2]-dithiolan-3-yl-pentanoic acid 3-(5-[1,2]-dithiolan-3yl-pentanoyloxy)-propyl ester (AN-8) augmented the rate glucose transport in myotubes in culture in the absence or presence of insulin. Their potency was 12-fold higher than that of the parent compound; their maximal stimulatory effect was 1.5-fold higher than that of LA. When tested in vivo in streptozotocin-diabetic C57/Black mice, AN-7 (10 mg/kg/day for 2 weeks, sc) reduced blood glucose level by 39% while a higher dose of LA (50 mg/kg/day for 2 weeks, sc) lowered it by 30%. These results indicate that AN-7 is more potent than LA in augmenting glucose transport in skeletal muscles and reducing blood glucose in diabetic animals. (C) 2003 Elsevier Ltd. All rights reserved.
• ANTIOXIDANT NANOSPHERE COMPRISING [1,2]-DITHIOLANE MOIETIES
  申请人：Yu John S.

  公开号：US20100291222A1

  公开（公告）日：2010-11-18

  The present invention is directed to multiple a-lipoic acid-containing hydrophobic compounds (mALAs) capable of acting as scavengers of free radicals, metals and reactive oxygen species (ROS). Methods of synthesizing novel antioxidant mALAs, spontaneous emulsification or nanoprecipitaion thereof to produce antioxidant nanospheres and their use in preventing or treating diseases or conditions caused by oxidative stress and other free radical mediated conditions are also described. Another aspect of this invention is the use of these antioxidant nanospheres for the preparation of antioxidant particulate delivery system of therapeutic agents.
• US9028874B2
  申请人：——

  公开号：US9028874B2

  公开（公告）日：2015-05-12