乙酰基洛伐他汀 | 81189-92-6

• 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: 乙酰基洛伐他汀
• 英文名称: (S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-acetoxy-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester
• 英文别名: O-acetylmonacolin K；4-acetyl lovastatin；Acetyllovastatin；[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-acetyloxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate
• CAS: 81189-92-6
• 化学式: C₂₆H₃₈O₆
• 分子量: 446.584
• InChiKey: OYNSFDWALRRTFU-QQVNEASTSA-N

物化性质

• 沸点：
  568.9±50.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥250mg/mL（559.81mM）

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 安全说明：
  S26,S36

制备方法与用途

生物活性

Acetyllovastatin 是一种 Lovastatin 的乙酸盐，对乙酰胆碱酯酶有中度抑制作用，IC50 为 79 μg/mL。Lovastatin 具有抗真菌活性，并抑制许多转化细胞系的增殖。

靶点

IC50: 79 μg/mL (The enzyme acetylcholinesterase)

反应信息

• 作为反应物：
  描述：

  乙酰基洛伐他汀 在 羟胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以62%的产率得到(S)-2-methyl-butyric acid (3S,7S,8S,8aR)-8-[(3R,5R)-6-hydroxycarbamoyl-3-acetoxy-5-dihydroxy-hexyl]-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species

  摘要：

  Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40 mu M had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.005
• 作为产物：
  描述：

  乙酸酐 、 洛伐他汀 在 吡啶 作用下， 反应 2.5h， 以84%的产率得到乙酰基洛伐他汀
  参考文献：
  名称：

  Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species

  摘要：

  Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40 mu M had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.005

文献信息

• [EN] METHODS FOR MAKING SIMVASTATIN AND INTERMEDIATES<br/>[FR] PROCEDES POUR FABRIQUER LA SIMVASTATINE ET LEURS INTERMEDIAIRES
  申请人：DIVERSA CORP

  公开号：WO2005040107A3

  公开（公告）日：2009-02-12