statin II

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: statin II
• 英文别名: [(1S,3S,7S,8S,8aR)-3-(hydroxymethyl)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate
• 化学式: C₂₄H₃₆O₆
• 分子量: 420.546
• InChiKey: MYUBCUVTJUKGIS-WVGTXZNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  叔-丁氧基自由基 、 statin II 以 乙腈 为溶剂， 反应 15.0h， 生成 丙酮 、 叔丁醇
  参考文献：
  名称：

  Oxidation of HMG‐CoA Reductase Inhibitors by tert‐Butoxyl and 1,1‐Diphenyl‐2‐picrylhydrazyl Radicals: Model Reactions for Predicting Oxidatively Sensitive Compounds During Preformulation

  摘要：

  Hydrogen atom abstraction rate constants for the reaction of tert-butoxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical with the HMG-CoA reductase inhibitors lovastatin, simvastatin, and statins I-IV were measured. This series of diene-containing drugs is known to be prone to oxidation. The tert-butoxyl radical was generated by the thermolysis of di-tert-butylperoxyoxalate at 40 degreesC. A competitive kinetic method was used to determine the relative rate of hydrogen atom abstraction by tert-butoxyl radical to beta -scission. The absolute rate constants were calculated using the experimentally determined product ratios of t-butanol to acetone and the known rate of beta -scission of tert-butoxyl radical. The rate constants for the reaction with DPPN: radical were measured spectrophotometrically by monitoring the loss of DPPH radical as a function of substrate concentration. The rate constants correlate well with the structure of the molecules studied. These kinetic techniques allow for oxidatively sensitive compounds to be identified early in the drug development cycle. The tert-butoxyl radical, a strong hydrogen atom abstractor, is representative of the hydroxyl ( . OH) and alkoxyl ( . OR) radicals; in contrast the DPPH radical, a much weaker radical, is a good kinetic model for hydroperoxyl ( . OOH) and peroxyl ( . OOR) radicals. These kinetic methods can be used to quantitatively assess the lability of drug candidates towards reaction with oxygen-centered radicals at an early stage of development and facilitate the design of inhibiting strategies. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89:1518-1524, 2000.

  DOI：

  10.1002/1520-6017(200012)89:12<1518::aid-jps2>3.0.co;2-o