[1,1-difluoro-2-(5-hydroxy-4-hydroxymethyl-6-methylpyridin-3-yl)-2-oxoethyl]phosphonic acid diethyl ester | 357966-31-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [1,1-difluoro-2-(5-hydroxy-4-hydroxymethyl-6-methylpyridin-3-yl)-2-oxoethyl]phosphonic acid diethyl ester
• 英文别名: diethyl (3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridyl)-2-oxo-1,1-difluoroethylphosphonate；2-Diethoxyphosphoryl-2,2-difluoro-1-[5-hydroxy-4-(hydroxymethyl)-6-methylpyridin-3-yl]ethanone
• CAS: 357966-31-5
• 化学式: C₁₃H₁₈F₂NO₆P
• 分子量: 353.26
• InChiKey: UWNYTNXQIVPBDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [1,1-difluoro-2-(5-hydroxy-4-hydroxymethyl-6-methylpyridin-3-yl)-2-oxoethyl]phosphonic acid diethyl ester 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 以60%的产率得到[(3,7-Dihydroxy-6-methyl-1,3-dihydro-furo[3,4-c]pyridin-3-yl)-difluoromethyl]-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
• 作为产物：
  描述：

  alpha4,3-异亚丙基异吡哆醛 在 manganese(IV) oxide 、 溶剂黄146 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 23.17h， 生成 [1,1-difluoro-2-(5-hydroxy-4-hydroxymethyl-6-methylpyridin-3-yl)-2-oxoethyl]phosphonic acid diethyl ester
  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

• Cardioprotective phosphonates and malonates
  申请人：——

  公开号：US20040171588A1

  公开（公告）日：2004-09-02

  The present invention provides for pyridoxine phosphonate analogues, pharmaceutical compositions, and methods for treatment of cardiovascular and related diseases.

  本发明提供了吡哆醇膦酸类似物、制药组合物以及治疗心血管和相关疾病的方法。
• Treatment of cerebrovascular disease
  申请人：——

  公开号：US20010056081A1

  公开（公告）日：2001-12-27

  A method of treating a cerebrovascular disease, particularly stroke, is described. A method of treating a cerebrovascular disease includes administering pyridoxal-5′-phosphate, pyridoxal, pyridoxine, pyridoxamine, 3-acylated analogues of pyridoxal, 3-acylated analogues of pyridoxal-4,5-aminal, pyridoxine phosphonate analogues, or pharmaceutical compositions thereof.

  本发明涉及一种治疗脑血管疾病，特别是中风的方法。治疗脑血管疾病的方法包括给予吡哆醛-5'-磷酸、吡哆醛、吡哆醇、吡哆胺、吡哆醛的3-酰化类似物、吡哆醛-4,5-二胺的3-酰化类似物、吡哆醇磷酸酯类似物或其药物组合物。
• WO2006/58411
  申请人：——

  公开号：——

  公开（公告）日：——
• Modulation of cell death
  申请人：Friesen David Albert

  公开号：US20070032456A1

  公开（公告）日：2007-02-08

  A method of modulating cell death includes administering pyridoxal-5′phosphate, pyridoxal, pyridoxine, pyridoxamine, 3-acylated analogues of pyridoxal, 3-acylated analogues of pyridoxal-4,5-aminal, pyridoxine phosphonate analogues, or pharmaceutical compositions thereof.
• Compositions for treating angina
  申请人：REIMER James Dawson

  公开号：US20070167411A1

  公开（公告）日：2007-07-19

  A method of treating angina in a mammal includes administering pyridoxal-5′-phosphate, pyridoxal, pyridoxine, pyridoxamine, 3-acylated analogues of pyridoxal, 3-acylated analogues of pyridoxal-4,5-aminal, pyridoxine phosphonate analogues, or pharmaceutical compositions thereof.