1-[5',6'-dideoxy-6'-(dihydroxyphosphinyl)-β-D-ribohexofuranosyl]-5-(p-tolyl)uracil | 1365532-58-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 1-[5',6'-dideoxy-6'-(dihydroxyphosphinyl)-β-D-ribohexofuranosyl]-5-(p-tolyl)uracil
• 英文别名: 2-[(2R,3S,4R,5R)-3,4-dihydroxy-5-[5-(4-methylphenyl)-2,4-dioxopyrimidin-1-yl]oxolan-2-yl]ethylphosphonic acid
• CAS: 1365532-58-6
• 化学式: C₁₇H₂₁N₂O₈P
• 分子量: 412.336
• InChiKey: XPWLJVZHVNTSLI-IXYNUQLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  157
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (5',6'-dideoxy-6'-diethoxyphosphonate-2',3'-O-isopropylidene-β-D-ribo-hexofuranosyl)-1-uracil 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 三甲基溴硅烷 、 sodium carbonate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 1-[5',6'-dideoxy-6'-(dihydroxyphosphinyl)-β-D-ribohexofuranosyl]-5-(p-tolyl)uracil
  参考文献：
  名称：

  Synthesis and P2Y2 receptor agonist activities of uridine 5′-phosphonate analogues

  摘要：

  We explored the influence of modifications of uridine 5'-methylenephosphonate on biological activity at the human P2Y(2) receptor. Key steps in the synthesis of a series of 5-substituted uridine 5'-methylenephosphonates were the reaction of a suitably protected uridine 5'-aldehyde with [(diethoxyphosphinyl) methylidene] triphenylphosphorane, C-5 bromination and a Suzuki-Miyaura coupling. These analogues behaved as selective agonists at the P2Y(2) receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y(2) receptor. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.012

文献信息

• Synthesis and P2Y2 receptor agonist activities of uridine 5′-phosphonate analogues
  作者：Sara Van Poecke、Matthew O. Barrett、T. Santhosh Kumar、Davy Sinnaeve、José C. Martins、Kenneth A. Jacobson、T. Kendall Harden、Serge Van Calenbergh

  DOI：10.1016/j.bmc.2012.02.012

  日期：2012.4

  We explored the influence of modifications of uridine 5'-methylenephosphonate on biological activity at the human P2Y(2) receptor. Key steps in the synthesis of a series of 5-substituted uridine 5'-methylenephosphonates were the reaction of a suitably protected uridine 5'-aldehyde with [(diethoxyphosphinyl) methylidene] triphenylphosphorane, C-5 bromination and a Suzuki-Miyaura coupling. These analogues behaved as selective agonists at the P2Y(2) receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y(2) receptor. (C) 2012 Elsevier Ltd. All rights reserved.