[2-(2-Amino-phenyl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid | 427899-21-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: [2-(2-Amino-phenyl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid
• 英文别名: (2-(2-Aminophenyl)-1-hydroxy-1-phosphonoethyl)phosphonic acid；[2-(2-aminophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid
• CAS: 427899-21-6
• 化学式: C₈H₁₃NO₇P₂
• 分子量: 297.141
• InChiKey: VJXYJONFUZXZJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  161
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-硝基苯乙酸 在 palladium on activated charcoal 亚磷酸 、 氢气 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 80.0 ℃ 、413.68 kPa 条件下， 反应 5.0h， 生成 [2-(2-Amino-phenyl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid
  参考文献：
  名称：

  Bisphosphonate Inhibition of the Exopolyphosphatase Activity of the Trypanosoma brucei Soluble Vacuolar Pyrophosphatase

  摘要：

  Trypanosoma brucei, the causative agent of African trypanosomiasis, contains a soluble, vacuolar pyrophosphatase, TbVSP1, not present in humans, which is essential for the growth of bloodstream forms in their mammalian host. Here, we report the inhibition of a recombinant TbVSP1 expressed in Escherichia coli by a panel of 81 bisphosphonates. The IC50 values were found to vary from similar to 2 to 850 mu M. We then used 3D QSAR (comparative molecular field and comparative molecular similarity index; CoMFA and CoMSIA) methods to analyze the enzyme inhibition results. The R-2 values for the experimental versus the QSAR-predicted activities were 0.78 or 0.61 for CoMFA and 0.79 or 0.68 for CoMSIA, for two different alignments. The root-mean-square (rms) pIC(50) error for the best CoMFA model was 0.41 for five test sets of five activity predictions, which translates to a factor of similar to 2.6 error in IC50 prediction. For CoMSIA, the rms pIC(50) error and error factors were 0.35 and 2.2, respectively. In general, the most active compounds contained both a single aromatic ring and a hydrogen bond donor feature. Thirteen of the more potent compounds were then tested in vivo in a mouse model of T. brucei infection. The most active compound in vivo provided a 40% protection from death with no apparent side effects, suggesting that further development of such compounds may be of interest.

  DOI：

  10.1021/jm058220g

文献信息

• Bisphosphonate Inhibition of the Exopolyphosphatase Activity of the <i>Trypanosoma brucei</i> Soluble Vacuolar Pyrophosphatase
  作者：Evangelia Kotsikorou、Yongcheng Song、Julian M. W. Chan、Stephanie Faelens、Zev Tovian、Erin Broderick、Norbert Bakalara、Roberto Docampo、Eric Oldfield

  DOI：10.1021/jm058220g

  日期：2005.9.1

  Trypanosoma brucei, the causative agent of African trypanosomiasis, contains a soluble, vacuolar pyrophosphatase, TbVSP1, not present in humans, which is essential for the growth of bloodstream forms in their mammalian host. Here, we report the inhibition of a recombinant TbVSP1 expressed in Escherichia coli by a panel of 81 bisphosphonates. The IC50 values were found to vary from similar to 2 to 850 mu M. We then used 3D QSAR (comparative molecular field and comparative molecular similarity index; CoMFA and CoMSIA) methods to analyze the enzyme inhibition results. The R-2 values for the experimental versus the QSAR-predicted activities were 0.78 or 0.61 for CoMFA and 0.79 or 0.68 for CoMSIA, for two different alignments. The root-mean-square (rms) pIC(50) error for the best CoMFA model was 0.41 for five test sets of five activity predictions, which translates to a factor of similar to 2.6 error in IC50 prediction. For CoMSIA, the rms pIC(50) error and error factors were 0.35 and 2.2, respectively. In general, the most active compounds contained both a single aromatic ring and a hydrogen bond donor feature. Thirteen of the more potent compounds were then tested in vivo in a mouse model of T. brucei infection. The most active compound in vivo provided a 40% protection from death with no apparent side effects, suggesting that further development of such compounds may be of interest.