| 1190930-94-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• CAS: 1190930-94-9
• 化学式: C₄₉H₆₄N₆O₁₅
• 分子量: 977.078
• InChiKey: DZBYPKIHNGJYFI-GXKZDDDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.99
• 重原子数：
  70.0
• 可旋转键数：
  20.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  243.04
• 氢给体数：
  3.0
• 氢受体数：
  17.0

反应信息

• 作为反应物：
  描述：

  在 DT-diaphorase 、 还原型辅酶Ⅰ 作用下， 反应 24.0h， 生成 纳洛酮
  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：

  、 盐酸纳洛酮 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 以65 mg的产率得到
  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