[1,1-difluoro-2-oxo-2-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)ethyl]phosphonic acid diethyl ester | 357966-29-1

• 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-oxo-2-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)ethyl]phosphonic acid diethyl ester
• 英文别名: diethyl (α⁴,3-O-isopropylidene-3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridyl)-2-oxo-1,1-difluoroethylphosphonate；2-diethoxyphosphoryl-2,2-difluoro-1-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)ethanone
• CAS: 357966-29-1
• 化学式: C₁₆H₂₂F₂NO₆P
• 分子量: 393.324
• InChiKey: PTJWTZORMKSVAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [1,1-difluoro-2-oxo-2-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)ethyl]phosphonic acid diethyl ester 在 溶剂黄146 作用下， 反应 5.0h， 以53%的产率得到[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
• 作为产物：
  描述：

  alpha4,3-异亚丙基异吡哆醛 在 manganese(IV) oxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 18.17h， 生成 [1,1-difluoro-2-oxo-2-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)ethyl]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

• 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.
• Pyridoxal-5-Phosphate and Related Compounds in Combination With Therapeutic Cardiovascular Compounds for Treating Angina
  申请人：Friesen Albert

  公开号：US20080311099A1

  公开（公告）日：2008-12-18

  Methods for treating angina are described. A method for treating angina includes concurrently administering a compound with a therapeutic cardiovascular compound. A combination therapy employs suitable therapeutic cardiovascular compounds, such as a calcium channel blocker, a β-adrenergic blocker, nitrates, partial fatty acid oxidation inhibitors, potassium channel activators, or a mixture thereof, in combination with a compound such as pyridoxal-5′phosphate, pyridoxic acid, pyridoxal, pyridoxamine, 3-acylated analogues of pyridoxal, 3-acylated analogues of pyridoxal-4,5-aminal, pyridoxine phosphonate analogues, a pharmaceutically acceptable acid addition salt thereof, or a mixture thereof. The invention also includes a novel composition comprising at least one compound and nitrates, partial fatty acid oxidation inhibitors, potassium channel activators, calcium channel blockers, β-adrenergic blockers, or a mixture thereof.
• US7442689B2
  申请人：——

  公开号：US7442689B2

  公开（公告）日：2008-10-28