4-(((2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-6-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl))-4-oxobutanoic Acid | 1379478-16-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 黄酮木脂素
• 英文名称: 4-(((2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-6-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl))-4-oxobutanoic Acid
• 英文别名: silibinin hemisuccinate；4-[[(2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-6-[(2R,3R)-3,5,7-trihydroxy-4-oxo-2,3-dihydrochromen-2-yl]-2,3-dihydro-1,4-benzodioxin-2-yl]methoxy]-4-oxobutanoic acid
• CAS: 1379478-16-6
• 化学式: C₂₉H₂₆O₁₃
• 分子量: 582.518
• InChiKey: ISCNZRNWJQZFHN-FQZUIQCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  199
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  4-(((2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-6-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl))-4-oxobutanoic Acid 、 N1-(1,2,3,4-tetrahydroacridin-9-yl)hexane-1,6-diamine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 16.5h， 以59%的产率得到((2S,3S)-3-(4-Hydroxy-3-methoxyphenyl)-6-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)-methyl 4-oxo-4-(6-(1,2,3,4-tetrahydroacridin-9-ylamino)-hexylamino)butanoate Hydrochloride
  参考文献：
  名称：

  Tacrine-Silibinin Codrug Shows Neuro- and Hepatoprotective Effects in Vitro and Pro-Cognitive and Hepatoprotective Effects in Vivo

  摘要：

  A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, analyzing the influence on viability and mitochondria of hepatic stellate cells (HSC), the toxicity of the codrug was markedly reduced in comparison to that of tacrine. Using a neuronal cell line (HT-22), a neuroprotective effect against glutamate-induced toxicity could be observed that was absent for the 1:1 mixture of components. In subsequent in vivo experiments in rats, in contrast to the effects seen after tacrine treatment, after administration of the codrug no hepatotoxicity and no induction of the cytochrome P450 system were noticed. In a scopolamine-induced cognitive impairment model using Wistar rats, the codrug was as potent as tacrine in reversing memory dysfunction. The tacrine silibinin codrug shows high AChE and BChE inhibition, neuroprotective effects, lacks tacrine's hepatotoxicity in vitro and in vivo, and shows the same pro-cognitive effects in vivo as tacrine, being superior to the physical mixture of tacrine and silibinin in all these regards.

  DOI：

  10.1021/jm300246n
• 作为产物：
  描述：

  琥珀酸苄酯 、 silybin B 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 20.0h， 以40%的产率得到4-(((2S,3S)-3-(4-hydroxy-3-methoxyphenyl)-6-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl))-4-oxobutanoic Acid
  参考文献：
  名称：

  Tacrine-Silibinin Codrug Shows Neuro- and Hepatoprotective Effects in Vitro and Pro-Cognitive and Hepatoprotective Effects in Vivo

  摘要：

  A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, analyzing the influence on viability and mitochondria of hepatic stellate cells (HSC), the toxicity of the codrug was markedly reduced in comparison to that of tacrine. Using a neuronal cell line (HT-22), a neuroprotective effect against glutamate-induced toxicity could be observed that was absent for the 1:1 mixture of components. In subsequent in vivo experiments in rats, in contrast to the effects seen after tacrine treatment, after administration of the codrug no hepatotoxicity and no induction of the cytochrome P450 system were noticed. In a scopolamine-induced cognitive impairment model using Wistar rats, the codrug was as potent as tacrine in reversing memory dysfunction. The tacrine silibinin codrug shows high AChE and BChE inhibition, neuroprotective effects, lacks tacrine's hepatotoxicity in vitro and in vivo, and shows the same pro-cognitive effects in vivo as tacrine, being superior to the physical mixture of tacrine and silibinin in all these regards.

  DOI：

  10.1021/jm300246n