5-([1,2]dithiolan-3-yl)pentanoic acid N-{3-[5-([1,2]dithiolan-3-yl)pentanoylamino]propyl}amide | 691410-93-2

• 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-yl)pentanoic acid N-{3-[5-([1,2]dithiolan-3-yl)pentanoylamino]propyl}amide
• 英文别名: 5-(dithiolan-3-yl)-N-[3-[5-(dithiolan-3-yl)pentanoylamino]propyl]pentanamide
• CAS: 691410-93-2
• 化学式: C₁₉H₃₄N₂O₂S₄
• 分子量: 450.755
• InChiKey: QGUXZRFEKWOQQL-UHFFFAOYSA-N

物化性质

• 熔点：
  79-81 °C
• 沸点：
  702.1±43.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：10mg/mL； DMSO：20mg/mL； DMSO:PBS (pH 7.2)(1:4)：0.15 mg/ml；乙醇：2mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Thioctic acid 在 碳酸氢钠 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 96.0h， 生成 5-([1,2]dithiolan-3-yl)pentanoic acid N-{3-[5-([1,2]dithiolan-3-yl)pentanoylamino]propyl}amide
  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

• 硫辛酸衍生物的制备方法
  申请人：江苏同禾药业有限公司

  公开号：CN114105945A

  公开（公告）日：2022-03-01

  本申请属于药物合成技术领域，具体涉及一种硫辛酸衍生物的制备方法，包括如下步骤：（1）将N‑羟基琥珀酰亚胺与N,N’‑二环己基碳二亚胺溶于二氧六环得溶液A，将硫辛酸溶于二氧六环得溶液B，将溶液B滴加入溶液A，滴加完毕后继续反应24‑72 h，滤除沉淀，滤液蒸发得固体粉末，将固体粉末溶于2‑丙醇，放置过夜，过滤得白色沉淀，干燥得到白色粉末；（2）将1,3‑丙二胺或1,3‑丙二醇溶于二氧六环得溶液C，将白色粉末溶于二氧六环得溶液D，将溶液C滴加入溶液D，滴加完毕后继续反应4‑6 h，降至室温，过滤除去沉淀，将滤液蒸发得到固体残渣，将固体残渣溶于热的乙醇/二氯甲烷溶液中，过滤去除沉淀，将滤液蒸发得到固体粉末，即为硫辛酸衍生物。
• 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.
• ORALLY ADMINISTRABLE COMPOSITIONS COMPRISING AVOCADO/SOYBEAN UNSAPONIFIABLES AND LIPOIC ACID AND METHODS OF ADMINISTRATION
  申请人：Frondoza Carmelita

  公开号：US20120294960A1

  公开（公告）日：2012-11-22

  Methods comprising administration of: (i) avocado/soybean unsaponifiables and (ii) lipoic acid or derivatives thereof, to a mammalian or an avian subject are provided. This invention also relates to orally administrable compositions comprising avocado/soybean unsaponifiables and lipoic acid or derivatives thereof.