6-methyl-3-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)(1H)pyrimidine-2,4-dione | 24744-17-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 6-methyl-3-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)(1H)pyrimidine-2,4-dione
• 英文别名: 6-methyl-3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2,4(1H,3H)-pyrimidinedione；6-methyl-3-(tri-O-benzoyl-β-D-ribofuranosyl)-1H-pyrimidine-2,4-dione；3-(2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl)-6-methyl-1,2,3,4-tetrahydropyrimidin-2,4-dion；6-Methyl-3-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-uracil；6-Methyl-3-(2,3,5-tri-O-benzoyl-β-D-ribosyl)-uracil；6-Methyl-3-(tri-O-benzoyl-D-ribofuranosyl)-uracil；[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(6-methyl-2,4-dioxo-1H-pyrimidin-3-yl)oxolan-2-yl]methyl benzoate
• CAS: 24744-17-0
• 化学式: C₃₁H₂₆N₂O₉
• 分子量: 570.555
• InChiKey: RQTOJVOLWWIGAL-MIRJVGOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-methyl-3-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)(1H)pyrimidine-2,4-dione 在 磷酸三甲酯 、 sodium methylate 、 1,8-双二甲氨基萘 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 6-methyl-3-beta-D-ribofuranosyl(1H)pyrimidine-2,4-dione 5''-monophosphate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Uracil Nucleotide Derivatives and Analogues as Agonists at Human P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y(2), P2Y(4), and P2Y(6) stably expressed in 1321N1 astrocytoma cells. Substituents at N3 of UTP were poorly tolerated by P2Y2 and P2Y4 receptors. In contrast, a large phenacyl substituent at N3 of UDP was well tolerated by the P2Y6 receptor, yielding a potent and selective P2Y6 receptor agonist (3-phenacyl-UDP, EC50 = 70 nM, > 500-fold selective). The most potent and selective P2Y2 receptor agonist of the present series was 2-thio-UTP (EC50 = 50 nM, >= 30-fold selective vs P2Y(4) and P2Y6). All modifications at the uracil base of UTP led to a decrease in potency at the P2Y4 receptor. A beta,gamma-dichloromethylene modification in the triphosphate chain of 5-bromo-UTP was tolerated by all three receptor subtypes, thus opening up a new strategy to obtain ectonucleotide diphosphohydrolase- and phosphatase-resistant P2Y(2), P2Y(4), and P2Y(6) receptor agonists.

  DOI：

  10.1021/jm060848j
• 作为产物：
  描述：

  6-甲基尿嘧啶 在 三甲基氯硅烷 、 四氯化锡 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成 6-methyl-3-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)(1H)pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Uracil Nucleotide Derivatives and Analogues as Agonists at Human P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y(2), P2Y(4), and P2Y(6) stably expressed in 1321N1 astrocytoma cells. Substituents at N3 of UTP were poorly tolerated by P2Y2 and P2Y4 receptors. In contrast, a large phenacyl substituent at N3 of UDP was well tolerated by the P2Y6 receptor, yielding a potent and selective P2Y6 receptor agonist (3-phenacyl-UDP, EC50 = 70 nM, > 500-fold selective). The most potent and selective P2Y2 receptor agonist of the present series was 2-thio-UTP (EC50 = 50 nM, >= 30-fold selective vs P2Y(4) and P2Y6). All modifications at the uracil base of UTP led to a decrease in potency at the P2Y4 receptor. A beta,gamma-dichloromethylene modification in the triphosphate chain of 5-bromo-UTP was tolerated by all three receptor subtypes, thus opening up a new strategy to obtain ectonucleotide diphosphohydrolase- and phosphatase-resistant P2Y(2), P2Y(4), and P2Y(6) receptor agonists.

  DOI：

  10.1021/jm060848j

文献信息

• Vorbrueggen, Helmut; Krolikiewicz, Konrad; Bennua, Baerbel, Chemische Berichte, 1981, vol. 114, # 4, p. 1234 - 1255
  作者：Vorbrueggen, Helmut、Krolikiewicz, Konrad、Bennua, Baerbel

  DOI：——

  日期：——