hydroxytyrosol clofibric acid ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: hydroxytyrosol clofibric acid ester
• 英文别名: 3,4-dihydroxyphenethyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate；2-(3,4-Dihydroxyphenyl)ethyl 2-(4-chlorophenoxy)-2-methylpropanoate；2-(3,4-dihydroxyphenyl)ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
• 化学式: C₁₈H₁₉ClO₅
• 分子量: 350.799
• InChiKey: JCKVCPGFUVTECM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  羟基酪醇 在 4-二甲氨基吡啶 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 10.0h， 生成 hydroxytyrosol clofibric acid ester
  参考文献：
  名称：

  A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects

  摘要：

  Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.

  DOI：

  10.1016/j.bmcl.2018.06.010

文献信息

• 3,4-二羟基苯乙醇贝特羧酸酯类化合物及其 制备方法和应用
  申请人：西安交通大学

  公开号：CN105693517B

  公开（公告）日：2018-12-07

  本发明公开了3,4‑二羟基苯乙醇贝特羧酸酯类化合物及其制备方法和应用，属于生物医药技术领域。该化合物与贝特羧酸具有较大差异，但仍然具有降脂活性，并且同时降低TC、TG。此外，还能抗氧化应激保护血管内皮损伤等作用。本发明还公开了3,4‑二羟基苯乙醇贝特羧酸酯类化合物的制备方法，以3,4‑二羟基苯乙醇、溴苄和碳酸钾为反应原料，经回流反应、柱层析分离，制得3,4‑二苄氧基苯乙醇，再将3,4‑二苄氧基苯乙醇与贝特羧酸化合物、1‑(3‑二甲氨基丙基)‑3‑乙基碳二亚胺盐酸盐和4‑二甲氨基吡啶溶于N,N‑二甲基甲酰胺中反应，最后加入钯碳催化，经清洁翻译后，制得羟基酪醇贝特羧酸酯类化合物。反应操作简单、对设备要求低，环境友好。
• A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects
  作者：Yun-Dong Xie、Zi-Zhang Chen、Li-Hua Shao、Qiu-Tang Wang、Na Li、Wen-Fang Lu、Yan-Hong Xu、Yu-Qiong Gao、Li-Ying Guo、Hao-Le Liu、Yi-Ping Li、Guang-De Yang、Xiao-Li Bian

  DOI：10.1016/j.bmcl.2018.06.010

  日期：2018.10

  Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.