(1-(2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14-diazahexadecan-16-yl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl methyl(2-(methylamino)ethyl)carbamate | 1190931-04-4

• 分子结构分类: 有机化合物
• 英文名称: (1-(2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14-diazahexadecan-16-yl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl methyl(2-(methylamino)ethyl)carbamate
• CAS: 1190931-04-4
• 化学式: C₂₉H₄₅N₅O₁₀
• 分子量: 623.704
• InChiKey: SCMLEOOZMALNJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  44.0
• 可旋转键数：
  17.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  175.76
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  三光气 、 (1-(2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14-diazahexadecan-16-yl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl methyl(2-(methylamino)ethyl)carbamate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Human plasma-mediated hypoxic activation of indolequinone-based naloxone pro-drugs

  摘要：

  Hypoxia is known to occur in tissues in response to narcotic analgesic therapy using as a result of respiratory depression. The aim of this study was to synthesize a narcotic antagonist pro-drug that can be activated by tissue hypoxia to prevent the damage associated with respiratory depression. We synthesized three different pro-drugs of the narcotic antagonist naloxone utilizing indolequinone as the hypoxia-sensitive moiety. The indolequinone structure in the pro-drugs was designed to have an open reactive point at the N-1 position offering the possibility of further conjugation with macromolecules to modify the bio-availability of these pro-drugs in vivo. A pro-drug (labeled 1) where naloxone and the indolequinone moiety were linked through a carbonate bond was rapidly hydrolyzed in phosphate buffered saline. However, two additional pro-drugs (labeled 2 and 3) having carbamate linkers were stable in phosphate buffered saline for 24 h. The reductive release of naloxone from the pro-drugs was achieved in the presence of the bio-reductive enzyme DT-Diaphorase, with about 80% release occurring from the two pro-drugs in 24 h. More than 99% of naloxone was released from pro-drug 2 in 30% human plasma, however the release only occurred under hypoxic conditions. This system provides a potential means for feedback control to counter critical respiratory depression induced by narcotic analgesics. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.061
• 作为产物：
  描述：

  tert-butyl (2-(2-(2-(2-(5-methoxy-2-methyl-3-((((4-nitrophenoxy)carbonyl)oxy)methyl)-4,7-dioxo-4,7-dihydro-1H-indol-1-yl)acetamido)ethoxy)ethoxy)ethyl)carbamate 、 N,N'-二甲基乙二胺 以 四氢呋喃 为溶剂， 以84%的产率得到(1-(2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14-diazahexadecan-16-yl)-5-methoxy-2-methyl-4,7-dioxo-4,7-dihydro-1H-indol-3-yl)methyl methyl(2-(methylamino)ethyl)carbamate
  参考文献：
  名称：

  Human plasma-mediated hypoxic activation of indolequinone-based naloxone pro-drugs

  摘要：

  Hypoxia is known to occur in tissues in response to narcotic analgesic therapy using as a result of respiratory depression. The aim of this study was to synthesize a narcotic antagonist pro-drug that can be activated by tissue hypoxia to prevent the damage associated with respiratory depression. We synthesized three different pro-drugs of the narcotic antagonist naloxone utilizing indolequinone as the hypoxia-sensitive moiety. The indolequinone structure in the pro-drugs was designed to have an open reactive point at the N-1 position offering the possibility of further conjugation with macromolecules to modify the bio-availability of these pro-drugs in vivo. A pro-drug (labeled 1) where naloxone and the indolequinone moiety were linked through a carbonate bond was rapidly hydrolyzed in phosphate buffered saline. However, two additional pro-drugs (labeled 2 and 3) having carbamate linkers were stable in phosphate buffered saline for 24 h. The reductive release of naloxone from the pro-drugs was achieved in the presence of the bio-reductive enzyme DT-Diaphorase, with about 80% release occurring from the two pro-drugs in 24 h. More than 99% of naloxone was released from pro-drug 2 in 30% human plasma, however the release only occurred under hypoxic conditions. This system provides a potential means for feedback control to counter critical respiratory depression induced by narcotic analgesics. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.061