1H-Azepine-1-acetic acid,2,3,4,7-tetrahydro-6-(hydroxymethyl)-3-[(2-naphthalenylcarbonyl)amino]-2-oxo-, methyl ester, (3S)- | 927907-11-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1H-Azepine-1-acetic acid,2,3,4,7-tetrahydro-6-(hydroxymethyl)-3-[(2-naphthalenylcarbonyl)amino]-2-oxo-, methyl ester, (3S)-
• 英文别名: (S)-methyl 2-(3-(2-naphthamido)-6-(hydroxymethyl)-2-oxo-3,4-dihydro-2H-azepin-1(7H)-yl)acetate
• CAS: 927907-11-7
• 化学式: C₂₁H₂₂N₂O₅
• 分子量: 382.416
• InChiKey: CDCFOSZTMLMVAS-SFHVURJKSA-N

物化性质

• 沸点：
  700.6±60.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  95.94
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1H-Azepine-1-acetic acid,2,3,4,7-tetrahydro-6-(hydroxymethyl)-3-[(2-naphthalenylcarbonyl)amino]-2-oxo-, methyl ester, (3S)- 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and evaluation of unsaturated caprolactams as interleukin-1β converting enzyme (ICE) inhibitors

  摘要：

  Peptidomimetic compounds possessing a caprolactam ring constraint were prepared and evaluated as interleukin-1 beta converting enzyme (ICE) inhibitors. The caprolactam ring was used to constrain the P3 region of our inhibitors. This strategy proved to be effective for the synthesis of ICE inhibitors, maintaining key hydrogen bond interactions with the enzyme and invoking a preferred conformation for binding. Several compounds exhibited IC50 values less than 10 nM in a caspase-1 enzyme assay and less than 100 nM in a THP-1 whole cell assay measuring IL-1 beta production. Two compounds, 13c and 13j, were found to have good oral bioavailability (> 50%) in rats when administered as prodrugs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.011
• 作为产物：
  描述：

  (S)-methyl 2-(3-(tert-butoxycarbonylamino)-6-((tert-butyldimethylsilyloxy)methyl)-2-oxo-3,4-dihydro-2H-azepin-1(7H)-yl)acetate 、 2-萘甲酰氯 在 三氟乙酸 、 三乙胺 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 0.67h， 以89%的产率得到1H-Azepine-1-acetic acid,2,3,4,7-tetrahydro-6-(hydroxymethyl)-3-[(2-naphthalenylcarbonyl)amino]-2-oxo-, methyl ester, (3S)-
  参考文献：
  名称：

  Synthesis and evaluation of unsaturated caprolactams as interleukin-1β converting enzyme (ICE) inhibitors

  摘要：

  Peptidomimetic compounds possessing a caprolactam ring constraint were prepared and evaluated as interleukin-1 beta converting enzyme (ICE) inhibitors. The caprolactam ring was used to constrain the P3 region of our inhibitors. This strategy proved to be effective for the synthesis of ICE inhibitors, maintaining key hydrogen bond interactions with the enzyme and invoking a preferred conformation for binding. Several compounds exhibited IC50 values less than 10 nM in a caspase-1 enzyme assay and less than 100 nM in a THP-1 whole cell assay measuring IL-1 beta production. Two compounds, 13c and 13j, were found to have good oral bioavailability (> 50%) in rats when administered as prodrugs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.011