cis-4-phenoxy-6-oxa-1-aza-bicyclo[3.2.1]octane-7-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: cis-4-phenoxy-6-oxa-1-aza-bicyclo[3.2.1]octane-7-one
• 英文别名: cis-4-phenoxy-6-oxa-1-azabicyclo[3.2.1]octan-7-one；(1R,2S)-2-phenoxy-7-oxa-5-aza-bicyclo[3.2.1]octan-6-one；(4S,5R)-4-phenoxy-6-oxa-1-azabicyclo[3.2.1]octan-7-one
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: GCWIICJLIHIUNY-WDEREUQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,2,3,6-四氢吡啶 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 sodium hydride 、 sodium carbonate 、 三乙胺 、 间氯过氧苯甲酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 129.0h， 生成 cis-4-phenoxy-6-oxa-1-aza-bicyclo[3.2.1]octane-7-one
  参考文献：
  名称：

  Bicyclic carbamates as inhibitors of papain-like cathepsin proteases

  摘要：

  A 6-oxa-1-aza-bicyclo[3.2.1]octan-7-one system inhibits the proteolytic activity of several cysteine proteases belonging to the papain family. In vitro mechanistic studies and in silico calculations suggest that the minimal pi-overlap between the bridgehead nitrogen and the carbonyl leads to a considerable weakening of the urethane system, making it susceptible to nucleophilic attack from the active site thiol group. The resulting covalent adduct is slowly hydrolyzed, releasing the hydroxypiperidine product of the inhibitor. Synthesis and testing of a set of analogs led to variable protease subtype selectivities ranging from micromolar to nanomolar potencies. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.014

文献信息

• Bicyclic carbamates as inhibitors of papain-like cathepsin proteases
  作者：Robert Epple、Hugo D. Urbina、Ross Russo、Hong Liu、Daniel Mason、Badry Bursulaya、Christine Tumanut、Jun Li、Jennifer L. Harris

  DOI：10.1016/j.bmcl.2006.12.014

  日期：2007.3

  A 6-oxa-1-aza-bicyclo[3.2.1]octan-7-one system inhibits the proteolytic activity of several cysteine proteases belonging to the papain family. In vitro mechanistic studies and in silico calculations suggest that the minimal pi-overlap between the bridgehead nitrogen and the carbonyl leads to a considerable weakening of the urethane system, making it susceptible to nucleophilic attack from the active site thiol group. The resulting covalent adduct is slowly hydrolyzed, releasing the hydroxypiperidine product of the inhibitor. Synthesis and testing of a set of analogs led to variable protease subtype selectivities ranging from micromolar to nanomolar potencies. (c) 2006 Elsevier Ltd. All rights reserved.