diethyl ((2-((benzyloxy)(methyl)amino)-2-oxoethoxy)(3,4-dichlorophenyl)methyl)phosphonate | 1386395-40-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diethyl ((2-((benzyloxy)(methyl)amino)-2-oxoethoxy)(3,4-dichlorophenyl)methyl)phosphonate
• CAS: 1386395-40-9
• 化学式: C₂₁H₂₆Cl₂NO₆P
• 分子量: 490.32
• InChiKey: HVOWCUNYCBMECR-UHFFFAOYSA-N

物化性质

• 沸点：
  566.4±60.0 °C(predicted)
• 密度：
  1.300±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.86
• 重原子数：
  31.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  74.3
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  diethyl ((2-((benzyloxy)(methyl)amino)-2-oxoethoxy)(3,4-dichlorophenyl)methyl)phosphonate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 以92%的产率得到diethyl ((3,4-dichlorophenyl)(2-(hydroxy(methyl)amino)-2-oxoethoxy)methyl)phosphonate
  参考文献：
  名称：

  α-Substituted β-Oxa Isosteres of Fosmidomycin: Synthesis and Biological Evaluation

  摘要：

  Specific inhibition of enzymes of the non-mevalonate pathway is a promising strategy for the development of novel antiplasmodial drugs. alpha-Aryl-substituted beta-oxa isosteres of fosmidomycin with a reverse orientation of the hydroxamic acid group were synthesized and evaluated for their inhibitory activity against recombinant 1-deoxy-D-xylulose 5-phosphate reductoisomerase (IspC) of Plasmodium falciparum and for their in vitro antiplasmodial activity against chloroquine-sensitive and resistant strains of P. falciparum. The most active derivative inhibits IspC protein of P. falciparum (PfIspC) with an IC50 value of 12 nM and shows potent in vitro antiplasmodial activity. In addition, lipophilic ester prodrugs demonstrated improved P. falciparum growth inhibition in vitro.

  DOI：

  10.1021/jm300652f
• 作为产物：
  描述：

  diethyl [(3,4-dichlorophenyl)(hydroxy)methyl]phosphonate 在 palladium 10% on activated carbon 、 氢气 、 N,N'-羰基二咪唑 、 silver(l) oxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 38.0h， 生成 diethyl ((2-((benzyloxy)(methyl)amino)-2-oxoethoxy)(3,4-dichlorophenyl)methyl)phosphonate
  参考文献：
  名称：

  α-Substituted β-Oxa Isosteres of Fosmidomycin: Synthesis and Biological Evaluation

  摘要：

  Specific inhibition of enzymes of the non-mevalonate pathway is a promising strategy for the development of novel antiplasmodial drugs. alpha-Aryl-substituted beta-oxa isosteres of fosmidomycin with a reverse orientation of the hydroxamic acid group were synthesized and evaluated for their inhibitory activity against recombinant 1-deoxy-D-xylulose 5-phosphate reductoisomerase (IspC) of Plasmodium falciparum and for their in vitro antiplasmodial activity against chloroquine-sensitive and resistant strains of P. falciparum. The most active derivative inhibits IspC protein of P. falciparum (PfIspC) with an IC50 value of 12 nM and shows potent in vitro antiplasmodial activity. In addition, lipophilic ester prodrugs demonstrated improved P. falciparum growth inhibition in vitro.

  DOI：

  10.1021/jm300652f