1-[Chloro(2-ethoxyethoxy)phosphoryl]-4-methoxybenzene | 362474-31-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[Chloro(2-ethoxyethoxy)phosphoryl]-4-methoxybenzene
• CAS: 362474-31-5
• 化学式: C₁₁H₁₆ClO₄P
• 分子量: 278.672
• InChiKey: ZYOFHPCEKIWCHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[Chloro(2-ethoxyethoxy)phosphoryl]-4-methoxybenzene 在 10percent Pd/C 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 (3R)-N-hydroxy-2-[(R)-(2-ethoxyethyloxy)(4-methoxyphenyl)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：

  1-[Bis(2-ethoxyethoxy)phosphoryl]-4-methoxybenzene 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 反应 3.0h， 生成 1-[Chloro(2-ethoxyethoxy)phosphoryl]-4-methoxybenzene
  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

文献信息

• New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids
  作者：Masaaki Sawa、Takao Kiyoi、Kiriko Kurokawa、Hiroshi Kumihara、Minoru Yamamoto、Tomohiro Miyasaka、Yasuko Ito、Ryoichi Hirayama、Tomomi Inoue、Yasuyuki Kirii、Eiji Nishiwaki、Hiroshi Ohmoto、Yu Maeda、Etsuko Ishibushi、Yoshimasa Inoue、Kohichiro Yoshino、Hirosato Kondo

  DOI：10.1021/jm0103211

  日期：2002.2.1

  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.