5-O-[5,7-dichloro-1-(2-oxo-1-phenyl-pyrrolidin-3-ylidenemethyl)-1H-indene-2-carboxylate]-ribofuranosyl adenine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 5-O-[5,7-dichloro-1-(2-oxo-1-phenyl-pyrrolidin-3-ylidenemethyl)-1H-indene-2-carboxylate]-ribofuranosyl adenine
• 英文别名: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl 4,6-dichloro-3-[(E)-(2-oxo-1-phenylpyrrolidin-3-ylidene)methyl]-1H-indole-2-carboxylate
• 化学式: C₃₀H₂₅Cl₂N₇O₆
• 分子量: 650.478
• InChiKey: QQVCAGRKLZDDDP-GKRZIOIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  182
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4,6-二氯-3-[(E)-(2-氧代-1-苯基-3-吡咯烷基亚基)甲基]-1H-吲哚-2-羧酸 在 四丁基溴化铵 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 5-O-[5,7-dichloro-1-(2-oxo-1-phenyl-pyrrolidin-3-ylidenemethyl)-1H-indene-2-carboxylate]-ribofuranosyl adenine
  参考文献：
  名称：

  Synthesis and biological evaluation of pro-drugs of GW196771, a potent glycine antagonist acting at the NMDA receptor

  摘要：

  GW196771 is a potent antagonist of the modulatory glycine site of the N-methyl-D-aspartate (NMDA) receptor exhibiting outstanding in vivo profile in different animal models of chronic pain. With the aim to maximize the drug delivery to the target organs a suitable "pro-drug approach" was attempted; in this regards two conjugates of GW196771 with nutrients actively transported into the brain, namely adenosine and glucose, were prepared and investigated. These compounds, were evaluated in vitro in terms of their stability in rat plasma and in vivo on rats. Although an improvement was observed in terms of brain penetration of the esters vs. the parent compound, the amount of the latter did not increase significantly, probably due to some degradation events in the brain, different from the expected ester hydrolysis, resulting in a reduced availability of GW196771.

  DOI：

  10.1016/j.farmac.2005.03.007

文献信息

• Synthesis and biological evaluation of pro-drugs of GW196771, a potent glycine antagonist acting at the NMDA receptor
  作者：Angela Angusti、Elisa Durini、Silvia Vertuani、Alessandro Dalpiaz、A. Ruffo、Romano Di Fabio、Daniele Donati、Giorgio Pentassuglia、Giovanni Vitulli、Robert J. Barnaby、Stefano Manfredini

  DOI：10.1016/j.farmac.2005.03.007

  日期：2005.5

  GW196771 is a potent antagonist of the modulatory glycine site of the N-methyl-D-aspartate (NMDA) receptor exhibiting outstanding in vivo profile in different animal models of chronic pain. With the aim to maximize the drug delivery to the target organs a suitable "pro-drug approach" was attempted; in this regards two conjugates of GW196771 with nutrients actively transported into the brain, namely adenosine and glucose, were prepared and investigated. These compounds, were evaluated in vitro in terms of their stability in rat plasma and in vivo on rats. Although an improvement was observed in terms of brain penetration of the esters vs. the parent compound, the amount of the latter did not increase significantly, probably due to some degradation events in the brain, different from the expected ester hydrolysis, resulting in a reduced availability of GW196771.