methyl 5-deoxy-5-chloro-2,3-di-O-benzoyl-D-ribofuranoside | 151378-78-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-deoxy-5-chloro-2,3-di-O-benzoyl-D-ribofuranoside
• CAS: 151378-78-8
• 化学式: C₂₀H₁₉ClO₆
• 分子量: 390.82
• InChiKey: VBVWLFCYGPJAEL-GXIXOUGGSA-N

物化性质

• 沸点：
  511.0±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  71.06
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 5-deoxy-5-chloro-2,3-di-O-benzoyl-D-ribofuranoside 在 叠氮化锂 、 三氟化硼乙醚 、 sodium methylate 作用下， 以 甲醇 、 硝基甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.75h， 生成 4-amino-3-iodo-1-(5-deoxy-5-azido-β-D-ribofuranosyl)pyrazolo<3,4-d>pyrimidine
  参考文献：
  名称：

  New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation

  摘要：

  Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino greater-than-or-equal-to deoxy > fluoro> chloro >> azido. The K(i) values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

  DOI：

  10.1021/jm00074a024
• 作为产物：
  描述：

  methyl 5-deoxy-5-chloro-2,3-O-sulfinyl-D-ribofuranoside 在 吡啶 、 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 methyl 5-deoxy-5-chloro-2,3-di-O-benzoyl-D-ribofuranoside
  参考文献：
  名称：

  New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation

  摘要：

  Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino greater-than-or-equal-to deoxy > fluoro> chloro >> azido. The K(i) values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

  DOI：

  10.1021/jm00074a024