sodium D-2-deoxy-2-acetamidoglucose-1-phosphate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: sodium D-2-deoxy-2-acetamidoglucose-1-phosphate
• 英文别名: sodium (2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl hydrogenphosphate；sodium;[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl] hydrogen phosphate
• 化学式: C₈H₁₅NO₉P*Na
• 分子量: 323.172
• InChiKey: WUXSMKYWTWDCEV-TVLNMICESA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -6.59
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  169
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  三正丁胺 、 sodium D-2-deoxy-2-acetamidoglucose-1-phosphate 在 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 P1-(uridine-5'-)P4-(2'-deoxy-2'-acetaminoglucose-1'-)tetraphosphate triethylammonium
  参考文献：
  名称：

  Pyrimidine Nucleotides with 4-Alkyloxyimino and Terminal Tetraphosphate δ-Ester Modifications as Selective Agonists of the P2Y₄ Receptor

  摘要：

  P2Y(2) and P2Y(4) receptors are G protein-coupled receptors, activated by UTP and dinudeoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5'-triphosphates and 5'-tetraphosphate esters. P2Y(4) receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N-4-alkyloxycytidine derivatives. OH groups on a terminal delta-glucose phosphoester of uridine 5'-tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N-4-(Phenylpropoxy)-CTP 16 (MRS4062), Up(4)-[1]3'-deoxy-3'-fluoroglucose 34 (MRS2927), and N-4-(phenylethoxy)-CTP 15 exhibit >= 10-fold selectivity for human P2Y(4) over P2Y(2) and P2Y(6) receptors (EC50 values 23, 62, and 73 nM, respectively). delta-3-Chlorophenyl phosphoester 21 of Up(4) activated P2Y(2) but not P2Y(4) receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y(2) and P2Y(4) receptor models indicated greater steric tolerance of N-4-phenylpropoxy group at P2Y(4). Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y(4) receptor-selective agonists.

  DOI：

  10.1021/jm101591j

文献信息

• Pyrimidine Nucleotides with 4-Alkyloxyimino and Terminal Tetraphosphate δ-Ester Modifications as Selective Agonists of the P2Y₄ Receptor
  作者：Hiroshi Maruoka、M. P. Suresh Jayasekara、Matthew O. Barrett、Derek A. Franklin、Sonia de Castro、Nathaniel Kim、Stefano Costanzi、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm101591j

  日期：2011.6.23

  P2Y(2) and P2Y(4) receptors are G protein-coupled receptors, activated by UTP and dinudeoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5'-triphosphates and 5'-tetraphosphate esters. P2Y(4) receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N-4-alkyloxycytidine derivatives. OH groups on a terminal delta-glucose phosphoester of uridine 5'-tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N-4-(Phenylpropoxy)-CTP 16 (MRS4062), Up(4)-[1]3'-deoxy-3'-fluoroglucose 34 (MRS2927), and N-4-(phenylethoxy)-CTP 15 exhibit >= 10-fold selectivity for human P2Y(4) over P2Y(2) and P2Y(6) receptors (EC50 values 23, 62, and 73 nM, respectively). delta-3-Chlorophenyl phosphoester 21 of Up(4) activated P2Y(2) but not P2Y(4) receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y(2) and P2Y(4) receptor models indicated greater steric tolerance of N-4-phenylpropoxy group at P2Y(4). Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y(4) receptor-selective agonists.