butyl (3R,5R)-7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: butyl (3R,5R)-7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate
• 英文别名: butyl (3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate
• 化学式: C₃₇H₄₃FN₂O₅
• 分子量: 614.757
• InChiKey: MGYCETWIEYLTPX-FIRIVFDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  45
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  lipitor 、 正丁醇 在 硫酸 作用下， 反应 2.5h， 以93%的产率得到butyl (3R,5R)-7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate
  参考文献：
  名称：

  阿托伐他汀酯类药物的合成和评价，该药为人羧酸酯酶代谢激活的药物

  摘要：

  我们以中等至高收率合成了11种具有阿托伐他汀酯化羧酸部分的前药。我们发现，它们通过人类羧酸酯酶1（CES1）同工酶特别地经历了代谢激活。结果表明，阿托伐他汀的这些酯化合物具有在体内充当前药的潜力。

  DOI：

  10.1016/j.bmcl.2015.12.069

文献信息

• Discovery of atorvastatin as a tetramer stabilizer of nuclear receptor RXRα through structure-based virtual screening
  作者：Xin Wang、Shuyi Chong、Huiyun Lin、Zhiqiang Yan、Fengyu Huang、Zhiping Zeng、Xiaokun Zhang、Ying Su

  DOI：10.1016/j.bioorg.2019.01.007

  日期：2019.4

  Retinoid X receptor alpha (RXR alpha), a central member of the nuclear receptor superfamily and a key regulator of many signal transduction pathways, has been an attractive drug target. We previously discovered that an N-terminally truncated form of RXR alpha can be induced by specific ligands to form homotetramers, which, as a result of conformational selection, forms the basis for inhibiting the nongenomic activation of RXR alpha. Here, we report the identification and characterization of atorvastatin as a new RXR alpha tetramer stabilizer by using structure based virtual screening and demonstrate that virtual library screening can be used to aid in identifying RXR alpha ligands that can induce its tetramerization. In this study, docking was applied to screen the FDA-approved small molecule drugs in the DrugBank 4.0 collection. Two compounds were selected and purchased for testing. We showed that the selected atorvastatin could bind to RXR alpha to promote RXR alpha-LBD tetramerization. We also showed that atorvastatin possessed RXR alpha-dependent apoptotic effects. In addition, we used a chemical approach to aid in the studies of the binding mode of atorvastatin.