[difluoro-(5-hydroxy-4-hydroxymethyl-6-methylpyridin-3-yl)methyl]phosphonic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: [difluoro-(5-hydroxy-4-hydroxymethyl-6-methylpyridin-3-yl)methyl]phosphonic acid
• 英文别名: [difluoro-[5-hydroxy-4-(hydroxymethyl)-6-methylpyridin-3-yl]methyl]phosphonic acid
• 化学式: C₈H₁₀F₂NO₅P
• 分子量: 269.142
• InChiKey: XOBOXISLAASRMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [Difluoro-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)-methyl]-phosphonic acid di-tert-butyl ester 在 溶剂黄146 作用下， 以 水 为溶剂， 反应 18.0h， 以20 mg的产率得到[difluoro-(5-hydroxy-4-hydroxymethyl-6-methylpyridin-3-yl)methyl]phosphonic acid
  参考文献：
  名称：

  Design and Synthesis of Novel Pyridoxine 5‘-Phosphonates as Potential Antiischemic Agents

  摘要：

  On the basis of previous reports that the natural cofactor pyridoxal 5'-phosphate 1 appears to display cardioprotective properties, a series of novel mimetics of this cofactor were envisioned. As pyridoxal 5'-phosphate is a natural compound and is subject to biological degradation and elimination pathways, the objective was to generate active phosphonates that are potentially less light sensitive and more stable in vivo than the parent vitamer. Several phosphonates were designed and synthesized, and in particular, compounds 10 and 14 displayed similar biological traits to natural phosphate 1 in the rat model of regional myocardial ischemia and reperfusion. A reduction in infarct size was observed in animals treated with these compounds. In an effort to identify other relevant cardioprotective models in order to potentially define structure-activity relationships, these three compounds were tested in the rat working heart model. Compounds 1, 10, and 14 were compared to dichloroacetic acid (DCA) as positive control in this model. As with DCA, compounds 1, 10, and 14 were found to induce a shift from fatty acid oxidation toward glucose oxidation.

  DOI：

  10.1021/jm0300678

文献信息

• Design and Synthesis of Novel Pyridoxine 5‘-Phosphonates as Potential Antiischemic Agents
  作者：Vinh Pham、Wenlian Zhang、Vince Chen、Tara Whitney、John Yao、Doug Froese、Albert D. Friesen、James M. Diakur、Wasim Haque

  DOI：10.1021/jm0300678

  日期：2003.8.1

  On the basis of previous reports that the natural cofactor pyridoxal 5'-phosphate 1 appears to display cardioprotective properties, a series of novel mimetics of this cofactor were envisioned. As pyridoxal 5'-phosphate is a natural compound and is subject to biological degradation and elimination pathways, the objective was to generate active phosphonates that are potentially less light sensitive and more stable in vivo than the parent vitamer. Several phosphonates were designed and synthesized, and in particular, compounds 10 and 14 displayed similar biological traits to natural phosphate 1 in the rat model of regional myocardial ischemia and reperfusion. A reduction in infarct size was observed in animals treated with these compounds. In an effort to identify other relevant cardioprotective models in order to potentially define structure-activity relationships, these three compounds were tested in the rat working heart model. Compounds 1, 10, and 14 were compared to dichloroacetic acid (DCA) as positive control in this model. As with DCA, compounds 1, 10, and 14 were found to induce a shift from fatty acid oxidation toward glucose oxidation.