6-[4-(3,4-dichlorophenyl)piperazine-1-yl]-9-(β-D-ribofuranosyl)-9H-purine | 1365531-13-0

• 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: 6-[4-(3,4-dichlorophenyl)piperazine-1-yl]-9-(β-D-ribofuranosyl)-9H-purine
• 英文别名: (2R,3R,4S,5R)-2-[6-[4-(3,4-dichlorophenyl)piperazin-1-yl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 1365531-13-0
• 化学式: C₂₀H₂₂Cl₂N₆O₄
• 分子量: 481.338
• InChiKey: KNDVLKLKJYUJLN-WVSUBDOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  四乙酰核糖 在 甲醇 、 sodium methylate 、 silica gel 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 20.5h， 生成 6-[4-(3,4-dichlorophenyl)piperazine-1-yl]-9-(β-D-ribofuranosyl)-9H-purine
  参考文献：
  名称：

  Synthesis of Novel 6-(4-Substituted piperazine-1-yl)-9-(β-d-ribofuranosyl)purine Derivatives, Which Lead to Senescence-Induced Cell Death in Liver Cancer Cells

  摘要：

  Novel purine ribonucleoside analogues (9-13) containing a 4-substituted piperazine in the substituent at N-6 were synthesized and evaluated for their cytotoxicity on Huh7, HepG2, FOCUS, Mahlavu liver, MCF7 breast, and HCT116 colon carcinoma cell lines. The purine nucleoside analogues were analyzed initially by an anticancer drug-screening method based on a sulforhodamine B assay. Two nucleoside derivatives with promising cytotoxic activities (11 and 12) were further analyzed on the hepatoma cells. The N-6-(4-Trifluoromethylphenyl)piperazine analogue 11 displayed the best antitumor activity, with IC50 values between 5.2 and 9.2 mu M. Similar to previously described nucleoside analogues, compound 11 also interferes with cellular ATP reserves, possibly through influencing cellular kinase activities. Furthermore, the novel nucleoside analogue 11 was shown to induce senescence-associated cell death, as demonstrated by the SA beta-gal assay. The senescence-dependent cytotoxic effect of 11 was also confirmed through phosphorylation of the Rb protein by p15(INK4b) overexpression in the presence of this compound.

  DOI：

  10.1021/jm3001532

文献信息

• Synthesis of Novel 6-(4-Substituted piperazine-1-yl)-9-(β-<scp>d</scp>-ribofuranosyl)purine Derivatives, Which Lead to Senescence-Induced Cell Death in Liver Cancer Cells
  作者：Meral Tuncbilek、Ebru Bilget Guven、Tugce Onder、Rengul Cetin Atalay

  DOI：10.1021/jm3001532

  日期：2012.4.12

  Novel purine ribonucleoside analogues (9-13) containing a 4-substituted piperazine in the substituent at N-6 were synthesized and evaluated for their cytotoxicity on Huh7, HepG2, FOCUS, Mahlavu liver, MCF7 breast, and HCT116 colon carcinoma cell lines. The purine nucleoside analogues were analyzed initially by an anticancer drug-screening method based on a sulforhodamine B assay. Two nucleoside derivatives with promising cytotoxic activities (11 and 12) were further analyzed on the hepatoma cells. The N-6-(4-Trifluoromethylphenyl)piperazine analogue 11 displayed the best antitumor activity, with IC50 values between 5.2 and 9.2 mu M. Similar to previously described nucleoside analogues, compound 11 also interferes with cellular ATP reserves, possibly through influencing cellular kinase activities. Furthermore, the novel nucleoside analogue 11 was shown to induce senescence-associated cell death, as demonstrated by the SA beta-gal assay. The senescence-dependent cytotoxic effect of 11 was also confirmed through phosphorylation of the Rb protein by p15(INK4b) overexpression in the presence of this compound.