((((3,4-difluorophenyl)(2-(hydroxy(methyl)amino)-2-oxoethoxy)methyl)phosphoryl)bis(oxy))-bis(methylene) bis(2,2-dimethylpropanoate) | 1386395-69-2

• 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: ((((3,4-difluorophenyl)(2-(hydroxy(methyl)amino)-2-oxoethoxy)methyl)phosphoryl)bis(oxy))-bis(methylene) bis(2,2-dimethylpropanoate)
• 英文别名: [[(3,4-Difluorophenyl)-[2-[hydroxy(methyl)amino]-2-oxo-ethoxy]methyl]-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate；[[(3,4-difluorophenyl)-[2-[hydroxy(methyl)amino]-2-oxoethoxy]methyl]-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
• CAS: 1386395-69-2
• 化学式: C₂₂H₃₂F₂NO₁₀P
• 分子量: 539.467
• InChiKey: FSQFYCDSORKZHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  589.7±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)：
  3
• 重原子数：
  36
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  ((((3,4-difluorophenyl)(2-(hydroxy(methyl)amino)-2-oxoethoxy)methyl)phosphoryl)bis(oxy))-bis(methylene) bis(2,2-dimethylpropanoate) 、 异氰酸乙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以93%的产率得到(((1-(3,4-difluorophenyl)-5-methyl-4,7-dioxo-2,6-dioxa-5,8-diazadecyl)phosphoryl)bis(oxy))bis(methylene) bis(2,2-dimethylpropanoate)
  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：

  2-[(diethoxyphosphoryl)(3,4-difluorophenyl)methoxy]acetic acid 在 三甲基溴硅烷 、 palladium 10% on activated carbon 、 氢气 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 45.0h， 生成 ((((3,4-difluorophenyl)(2-(hydroxy(methyl)amino)-2-oxoethoxy)methyl)phosphoryl)bis(oxy))-bis(methylene) bis(2,2-dimethylpropanoate)
  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

文献信息

• α-Substituted β-Oxa Isosteres of Fosmidomycin: Synthesis and Biological Evaluation
  作者：Karin Brücher、Boris Illarionov、Jana Held、Serena Tschan、Andrea Kunfermann、Miriam K. Pein、Adelbert Bacher、Tobias Gräwert、Louis Maes、Benjamin Mordmüller、Markus Fischer、Thomas Kurz

  DOI：10.1021/jm300652f

  日期：2012.7.26

  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.