uridine-5'-β,γ-dichloromethylene triphosphate ammonium | 1309871-44-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: uridine-5'-β,γ-dichloromethylene triphosphate ammonium
• 英文别名: β,γ-CCl2-UTP
• CAS: 1309871-44-0
• 化学式: C₁₀H₁₅Cl₂N₂O₁₄P₃*H₃N
• 分子量: 568.092
• InChiKey: NSNJJNMLFKKLBP-IAIGYFSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  290.14
• 氢给体数：
  8.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  uridine-5'-β,γ-dichloromethylene triphosphate ammonium 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， 生成 uridine-5'-glucose-1'-β,γ-dichloromethylene 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
• 作为产物：
  描述：

  uridine-5'-monophosphate sodium 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 uridine-5'-β,γ-dichloromethylene triphosphate ammonium
  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

• An Improved Method for the Synthesis of Nucleoside Triphosphate Analogues
  作者：Samy Mohamady、David L. Jakeman

  DOI：10.1021/jo0518598

  日期：2005.12.1

  Nucleoside monophosphates, when activated by trifluoroacetic anhydride and N-methylimidazole, efficiently couple with a variety of electron-deficient diphosphonates in a reproducible and efficient manner (< 2 h, > 72% isolated yield). Unlike traditional methods for the preparation of nucleoside 5'-beta,gamma-methylenetriphosphate analogues, there is no requirement for predrying, or conversion to specific salt forms, of commercially available nucleoside monophosphate starting materials.