(5-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylcarbamoyl}-pentyl)-carbamic acid tert-butyl ester | 837430-77-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: (5-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylcarbamoyl}-pentyl)-carbamic acid tert-butyl ester
• CAS: 837430-77-0
• 化学式: C₃₈H₄₈N₂O₁₄
• 分子量: 756.804
• InChiKey: LPDJSSBKSQUMPQ-GUSWMZCDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  54.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  247.48
• 氢给体数：
  7.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  (5-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylcarbamoyl}-pentyl)-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 以80%的产率得到6-Amino-hexanoic acid {(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-yl}-amide
  参考文献：
  名称：

  An Antisense Oligodeoxynucleotide‐Doxorubicin Conjugate: Preparation and Its Reversal Multidrug Resistance of Human Carcinoma Cell Line In Vitro

  摘要：

  An antisense oligodeoxynucleotide-doxorubicin conjugate was synthesized by an aminocaproic acid linker. The synthetic conjugate was identified by HPLC analysis and UV-vis spectra. Properties of the conjugate in vitro conditions were investigated. The results demonstrated that the conjugate was remarkably stabilized by doxorubicin. When incubated in Dulbecco Phosphate-Buflered Saline (pH 7.4) at 37degreesC, the conjugate was more stable than doxorubicin or the mixture of doxorubicin and antisense oligodeoxynucleotide. When incubated in 10% fetal serum at 37degreesC, the conjugate showed a remarkable stabilization as compared to the unmodified oligodeoxynucleotide. Melting experiments demonstrated that the covalent attachment of doxorubicin strongly stabilized the binding of the oligodeoxynucleotide to its complementary sequence. In addition, in vitro reversion of multidrug resistance by the conjugate was assayed in a human carcinoma cell line (KB-A-1) resisting to doxorubicin. The result showed that the conjugate displayed very high reversal multdrug resistance activity in KB-A-1 cells in vitro. The conjugate lowered the IC50 value from 21.5 muM to 2.2 muM with a fold-reversal factor of 10. In contrast, a slight decrease of the IC50 value was observed when they combined with the "free" antisense oligodeoxynucleotide: the IC50 value was down from 21.5 muM to 16.8 muM. This study suggested that antisense oligodeoxynucleotide-doxorubicin conjugate might be helpful in multidrug resistance reversal.

  DOI：

  10.1081/ncn-200031419
• 作为产物：
  描述：

  6-氨基己酸 在 N-甲基吗啉 、 sodium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 生成 (5-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylcarbamoyl}-pentyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  An Antisense Oligodeoxynucleotide‐Doxorubicin Conjugate: Preparation and Its Reversal Multidrug Resistance of Human Carcinoma Cell Line In Vitro

  摘要：

  An antisense oligodeoxynucleotide-doxorubicin conjugate was synthesized by an aminocaproic acid linker. The synthetic conjugate was identified by HPLC analysis and UV-vis spectra. Properties of the conjugate in vitro conditions were investigated. The results demonstrated that the conjugate was remarkably stabilized by doxorubicin. When incubated in Dulbecco Phosphate-Buflered Saline (pH 7.4) at 37degreesC, the conjugate was more stable than doxorubicin or the mixture of doxorubicin and antisense oligodeoxynucleotide. When incubated in 10% fetal serum at 37degreesC, the conjugate showed a remarkable stabilization as compared to the unmodified oligodeoxynucleotide. Melting experiments demonstrated that the covalent attachment of doxorubicin strongly stabilized the binding of the oligodeoxynucleotide to its complementary sequence. In addition, in vitro reversion of multidrug resistance by the conjugate was assayed in a human carcinoma cell line (KB-A-1) resisting to doxorubicin. The result showed that the conjugate displayed very high reversal multdrug resistance activity in KB-A-1 cells in vitro. The conjugate lowered the IC50 value from 21.5 muM to 2.2 muM with a fold-reversal factor of 10. In contrast, a slight decrease of the IC50 value was observed when they combined with the "free" antisense oligodeoxynucleotide: the IC50 value was down from 21.5 muM to 16.8 muM. This study suggested that antisense oligodeoxynucleotide-doxorubicin conjugate might be helpful in multidrug resistance reversal.

  DOI：

  10.1081/ncn-200031419