tri-n-butylammonium-tri-n-octylammonium 5-OMe-uridine monophosphate salt | 1380336-73-1

• 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-OMe-uridine monophosphate salt
• CAS: 1380336-73-1
• 化学式: C₁₀H₁₅N₂O₁₀P*C₁₂H₂₇N*C₂₄H₅₁N
• 分子量: 893.239
• InChiKey: MDNMCOWZCMOXLG-DVHQBHFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.33
• 重原子数：
  61.0
• 可旋转键数：
  35.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  187.02
• 氢给体数：
  5.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  tri-n-butylammonium-tri-n-octylammonium 5-OMe-uridine monophosphate salt 在 N,N'-羰基二咪唑 、 magnesium chloride 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 26.0h， 以8%的产率得到
  参考文献：
  名称：

  UDP made a highly promising stable, potent, and selective P2Y6-receptor agonist upon introduction of a boranophosphate moiety

  摘要：

  P2Y(6) nucleotide receptor (P2Y(6)-R) plays important physiological roles, such as insulin secretion and reduction of intraocular pressure. However, this receptor is still lacking potent and selective agonists to be used as potential drugs. Here, we synthesized uracil nucleotides and dinucleotides, substituted at the C5 and/or P-alpha position with methoxy and/or borano groups, 18-22. Compound 18A, R-p isomer of 5-OMe-UDP(alpha-B), is the most potent and P2Y(6)-R selective agonist currently known (EC50 0.008 mu M) being 19-fold more potent than UDP and showing no activity at uridine nucleotide receptors, P2Y(2)- and P2Y(4)-R. Analogue 18A was highly chemically stable under conditions mimicking gastric juice acidity (t(1/2) = 16.9 h). It was more stable to hydrolysis by nucleotide pyrophosphatases (NPP1,3) than UDP (15% and 28% hydrolysis by NPP1 and NPP3, respectively, vs 50% and 51% hydrolysis of UDP) and metabolically stable in blood serum (t(1/2) = 17 vs 2.4, 11.9, and 21 h for UDP, 5-OMe-UDP, and UDP(alpha-B), respectively). This newly discovered highly potent and physiologically stable P2Y(6)-R agonist may be of future therapeutic potential. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.042

文献信息

• 5-OMe-UDP is a Potent and Selective P2Y₆-Receptor Agonist
  作者：Tamar Ginsburg-Shmuel、Michael Haas、Marlen Schumann、Georg Reiser、Ori Kalid、Noa Stern、Bilha Fischer

  DOI：10.1021/jm901450d

  日期：2010.2.25

  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).