[4-(Pyridin-4-yloxy)-phenyl]-phosphonic acid diethyl ester | 362477-43-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-(Pyridin-4-yloxy)-phenyl]-phosphonic acid diethyl ester
• 英文别名: 4-(4-Diethoxyphosphorylphenoxy)pyridine
• CAS: 362477-43-8
• 化学式: C₁₅H₁₈NO₄P
• 分子量: 307.286
• InChiKey: PJHQMVGBLGOLED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(Pyridin-4-yloxy)-phenyl]-phosphonic acid diethyl ester 在 10percent Pd/C 氯化亚砜 、 氢气 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (3R)-N-hydroxy-2-{(R)-ethoxy[4-(pyridine-4-yl-oxy)phenyl]phosphoryl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids

  摘要：

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

  DOI：

  10.1021/jm0103211
• 作为产物：
  描述：

  亚磷酸二乙酯 、 4-(4-bromophenoxy)pyridine 在 四(三苯基膦)钯 、 三乙胺 作用下， 生成 [4-(Pyridin-4-yloxy)-phenyl]-phosphonic acid diethyl ester
  参考文献：
  名称：

  New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids

  摘要：

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

  DOI：

  10.1021/jm0103211