2-(adamantan-1-yl)acetic-2,2-d2 acid

• 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: 2-(adamantan-1-yl)acetic-2,2-d2 acid
• 英文别名: 2-(1-Adamantyl)-2,2-dideuterioacetic acid；2-(1-adamantyl)-2,2-dideuterioacetic acid
• 化学式: C₁₂H₁₈O₂
• 分子量: 196.258
• InChiKey: AOTQGWFNFTVXNQ-RJSZUWSASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(adamantan-1-yl)acetic-2,2-d2 acid 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 苯 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Targeting Botulinum A Cellular Toxicity: A Prodrug Approach

  摘要：

  The botulinum neurotoxin light chain (LC) protease has become an important therapeutic target for postexposure treatment of botulism. Hydroxamic acid based small molecules have proven to be potent inhibitors of LC/A with nanomolar K-i values, yet they lack cellular activity conceivably due to low membrane permeability. To overcome this potential liability, we investigated two prodrug strategies, 1,4,2-dioxazole and carbamate, based on our 1-adamantylacetohydroxarnic acid scaffold. The 1,4,2-dioxazole prodrug did not demonstrate cellular activity, however, carbamates exhibited cellular potency with the most active compound displaying an EC50 value of 20 mu M. Cellular trafficking studies were conducted using a "fluorescently silent" prodrug that remained in this state until cellular uptake was complete, which allowed for visualization of the drug's release inside neuronal cells. In sum, this research sets the stage for future studies leveraging the specific targeting and delivery of these prodrugs, as well as other antibotulinum agents, into neuronal cells.

  DOI：

  10.1021/jm400873n
• 作为产物：
  描述：

  1-金刚烷乙酸 在 aluminum (III) chloride 、 氘代苯 作用下， 以 硝基苯 为溶剂， 反应 0.5h， 以75%的产率得到2-(adamantan-1-yl)acetic-2,2-d2 acid
  参考文献：
  名称：

  Targeting Botulinum A Cellular Toxicity: A Prodrug Approach

  摘要：

  The botulinum neurotoxin light chain (LC) protease has become an important therapeutic target for postexposure treatment of botulism. Hydroxamic acid based small molecules have proven to be potent inhibitors of LC/A with nanomolar K-i values, yet they lack cellular activity conceivably due to low membrane permeability. To overcome this potential liability, we investigated two prodrug strategies, 1,4,2-dioxazole and carbamate, based on our 1-adamantylacetohydroxarnic acid scaffold. The 1,4,2-dioxazole prodrug did not demonstrate cellular activity, however, carbamates exhibited cellular potency with the most active compound displaying an EC50 value of 20 mu M. Cellular trafficking studies were conducted using a "fluorescently silent" prodrug that remained in this state until cellular uptake was complete, which allowed for visualization of the drug's release inside neuronal cells. In sum, this research sets the stage for future studies leveraging the specific targeting and delivery of these prodrugs, as well as other antibotulinum agents, into neuronal cells.

  DOI：

  10.1021/jm400873n

文献信息

• Targeting Botulinum A Cellular Toxicity: A Prodrug Approach
  作者：Peter Šilhár、Lisa M. Eubanks、Hajime Seki、Sabine Pellett、Sacha Javor、William H. Tepp、Eric A. Johnson、Kim D. Janda

  DOI：10.1021/jm400873n

  日期：2013.10.24

  The botulinum neurotoxin light chain (LC) protease has become an important therapeutic target for postexposure treatment of botulism. Hydroxamic acid based small molecules have proven to be potent inhibitors of LC/A with nanomolar K-i values, yet they lack cellular activity conceivably due to low membrane permeability. To overcome this potential liability, we investigated two prodrug strategies, 1,4,2-dioxazole and carbamate, based on our 1-adamantylacetohydroxarnic acid scaffold. The 1,4,2-dioxazole prodrug did not demonstrate cellular activity, however, carbamates exhibited cellular potency with the most active compound displaying an EC50 value of 20 mu M. Cellular trafficking studies were conducted using a "fluorescently silent" prodrug that remained in this state until cellular uptake was complete, which allowed for visualization of the drug's release inside neuronal cells. In sum, this research sets the stage for future studies leveraging the specific targeting and delivery of these prodrugs, as well as other antibotulinum agents, into neuronal cells.