9-acetoxy-2-<2-deoxy-3,5-bis-O-(p-toluoyl)-β-D-ribofuranosyl>-5,11-dimethyl-6H-pyrido<4,3-b>carbazolium chloride | 103482-09-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 9-acetoxy-2-<2-deoxy-3,5-bis-O-(p-toluoyl)-β-D-ribofuranosyl>-5,11-dimethyl-6H-pyrido<4,3-b>carbazolium chloride
• 英文别名: 9-acetoxy-2-[2-deoxy-3,5-bis-O-(p-toluoyl)-β-D-ribofuranosyl]-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium chloride
• CAS: 103482-09-3
• 化学式: C₄₀H₃₇N₂O₇*Cl
• 分子量: 693.196
• InChiKey: YHVLDRSKLWNTNQ-DHPGCIRWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  50.0
• 可旋转键数：
  7.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  107.8
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  9-acetoxy-2-<2-deoxy-3,5-bis-O-(p-toluoyl)-β-D-ribofuranosyl>-5,11-dimethyl-6H-pyrido<4,3-b>carbazolium chloride 在 甲醇 、 氨 作用下， 反应 24.0h， 以76%的产率得到2-(2-deoxy-β-D-ribofuranosyl)-9-hydroxyellipticinium chloride
  参考文献：
  名称：

  Synthesis and antitumor activity of quaternary ellipticine glycosides, a series of novel and highly active antitumor agents

  摘要：

  A series of ellipticine glycosides [2-N-glycosyl quaternary pyridinium salts of three ellipticines: ellipticine (1), 9-methoxyellipticine (2), and 9-hydroxyellipticine (4)] were stereoselectively synthesized in good yields by an improved condensation reaction between ellipticines [1, 2, and 9-acetoxyellipticine (3)] and protected (peracylated and perbenzylated) glycosyl halides with cadmium carbonate, followed by deprotection. These glycosides were preliminarily evaluated for their antitumor activity in the L1210 leukemia system. Twenty-six (53%) of the 49 glycosides tested were curative, and five [9-hydroxyellipticine L-arabinopyranoside (41b), D-lyxofuranoside (43a), L-lyxopyranoside (44b), D-xylofuranoside (49a), and L-rhamnopyranoside (56)] were selected for extended evaluation on the basis of their high levels of activity. The structure-activity relationships are discussed. The selected glycosides showed remarkable activity in six different murine tumor systems with excellent therapeutic ratios; their efficacy surpassed that of doxorubicin against three of these systems. On the basis of these results and ease of formulation, the two glycosides 41b (SUN4599) and 49a (SUN5073) were selected for further preclinical evaluation and possible clinical development.

  DOI：

  10.1021/jm00402a007
• 作为产物：
  描述：

  1-Α-氯-3,5-二-O-对甲苯甲酰基-2-脱氧-D-呋喃核糖 、 9-acetyloxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole 在 无水碳酸镉 作用下， 以 硝基甲烷 为溶剂， 反应 0.25h， 以27%的产率得到9-acetoxy-2-<2-deoxy-3,5-bis-O-(p-toluoyl)-β-D-ribofuranosyl>-5,11-dimethyl-6H-pyrido<4,3-b>carbazolium chloride
  参考文献：
  名称：

  Synthesis and antitumor activity of quaternary ellipticine glycosides, a series of novel and highly active antitumor agents

  摘要：

  A series of ellipticine glycosides [2-N-glycosyl quaternary pyridinium salts of three ellipticines: ellipticine (1), 9-methoxyellipticine (2), and 9-hydroxyellipticine (4)] were stereoselectively synthesized in good yields by an improved condensation reaction between ellipticines [1, 2, and 9-acetoxyellipticine (3)] and protected (peracylated and perbenzylated) glycosyl halides with cadmium carbonate, followed by deprotection. These glycosides were preliminarily evaluated for their antitumor activity in the L1210 leukemia system. Twenty-six (53%) of the 49 glycosides tested were curative, and five [9-hydroxyellipticine L-arabinopyranoside (41b), D-lyxofuranoside (43a), L-lyxopyranoside (44b), D-xylofuranoside (49a), and L-rhamnopyranoside (56)] were selected for extended evaluation on the basis of their high levels of activity. The structure-activity relationships are discussed. The selected glycosides showed remarkable activity in six different murine tumor systems with excellent therapeutic ratios; their efficacy surpassed that of doxorubicin against three of these systems. On the basis of these results and ease of formulation, the two glycosides 41b (SUN4599) and 49a (SUN5073) were selected for further preclinical evaluation and possible clinical development.

  DOI：

  10.1021/jm00402a007