tri-n-butylammonium tri-n-octylammonium 5-fluoro-5'-monophosphate uridine | 1207531-01-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: tri-n-butylammonium tri-n-octylammonium 5-fluoro-5'-monophosphate uridine
• CAS: 1207531-01-8
• 化学式: C₉H₁₂FN₂O₉P*C₁₂H₂₇N*C₂₄H₅₁N
• 分子量: 881.203
• InChiKey: MZXUQLYUNDMZPB-COYPUJSKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.46
• 重原子数：
  60.0
• 可旋转键数：
  34.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  177.79
• 氢给体数：
  5.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  tri-n-butylammonium tri-n-octylammonium 5-fluoro-5'-monophosphate uridine 、 N,N'-羰基二咪唑 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N,N-dibutylbutan-1-amine;[(2R,3S,4R,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-imidazol-1-ylphosphinic acid
  参考文献：
  名称：

  5-OMe-UDP is a Potent and Selective P2Y₆-Receptor Agonist

  摘要：

  P2Y nucleotide receptors (P2Y-Rs) play Important physiological roles. However, most of the P2Y-R subtypes are still lacking potent and selective agonists and antagonists. Based on data mining analysis of binding interactions in 44 protein-uridine nucleos(t)ides complexes, we designed uracil nucleotides, substituted at the C5/C6 position. All C6-substituted derivatives were inactive at the P2Y(2,4,6)-Rs, while out of the C5-substituted analogues, only 5-OMe-UD(T)P showed activity. To rationalize the data, the ionization and conformation of these analogues were evaluated. The pK(a) values of most analogues Substituted at the C5/C6 positions were unaltered compared to UTP (pK(a) 9.42), except for 5-F-UTP nucleotide (pK(a) 7.85). C6-substituted analogues adopt the syn or high-syn conformations, which are disfavored by the receptors, while 5-OMe-UD(T)P adopt the favored anti. conformation. Furthermore, 5-OMe-UDP adopts the S sugar puckering, which is the conformation preferred by the P2Y(6)-R, but not the P2Y(2)- or P2Y(4)-Rs. 5-OMe-UDP fulfills the conformational and H-bonding requirements of P2Y(6)-R, thus, making a potent P2Y(6)-R agonist (EC50 0.08 mu M), more than UDP (EC50 0.14 mu M).

  DOI：

  10.1021/jm901450d