((2-(hydroxy(methyl)amino)-2-oxoethoxy)(naphthalen-1-yl)methyl)phosphonic acid | 1386395-58-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ((2-(hydroxy(methyl)amino)-2-oxoethoxy)(naphthalen-1-yl)methyl)phosphonic acid
• 英文别名: [[2-[Hydroxy(methyl)amino]-2-oxo-ethoxy]-(1-naphthyl)methyl]phosphonic acid；[[2-[hydroxy(methyl)amino]-2-oxoethoxy]-naphthalen-1-ylmethyl]phosphonic acid
• CAS: 1386395-58-9
• 化学式: C₁₄H₁₆NO₆P
• 分子量: 325.258
• InChiKey: RZCGPVVICRPZKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  diethyl hydroxy(naphthalen-1-yl)methylphosphonate 在 三甲基溴硅烷 、 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 65.0h， 生成 ((2-(hydroxy(methyl)amino)-2-oxoethoxy)(naphthalen-1-yl)methyl)phosphonic acid
  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.