(3S)-N-benzyloxy-2-[(RS)-ethoxy(4-methoxyphenyl)phosphoryl]-1,2,3,4-tetrahydroisoquinole-3-carboxamide | 405175-81-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S)-N-benzyloxy-2-[(RS)-ethoxy(4-methoxyphenyl)phosphoryl]-1,2,3,4-tetrahydroisoquinole-3-carboxamide
• CAS: 405175-81-7
• 化学式: C₂₆H₂₉N₂O₅P
• 分子量: 480.5
• InChiKey: KMPGTWMBWHXSQO-VOTTXDMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  34.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  77.1
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (3S)-N-benzyloxy-2-[(RS)-ethoxy(4-methoxyphenyl)phosphoryl]-1,2,3,4-tetrahydroisoquinole-3-carboxamide 在 10percent Pd/C 氢气 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以25%的产率得到(3S)-2-[ethoxy-(4-methoxyphenyl)phosphoryl]-N-hydroxy-3,4-dihydro-1H-isoquinoline-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：

  (3S)-N-benzyloxy-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinole-3-carboxamide 在 吡啶 、 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 3.25h， 生成 (3S)-N-benzyloxy-2-[(RS)-ethoxy(4-methoxyphenyl)phosphoryl]-1,2,3,4-tetrahydroisoquinole-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