2'-trifluoroacetylamino-2'-deoxy-2-thiouridine | 934014-12-7

• 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: 2'-trifluoroacetylamino-2'-deoxy-2-thiouridine
• 英文别名: 2,2,2-trifluoro-N-[(2R,3R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-2-(4-oxo-2-sulfanylidenepyrimidin-1-yl)oxolan-3-yl]acetamide
• CAS: 934014-12-7
• 化学式: C₁₁H₁₂F₃N₃O₅S
• 分子量: 355.295
• InChiKey: UVKDBNQPBGCYFS-XVFCMESISA-N

物化性质

• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2'-trifluoroacetylamino-2'-deoxy-2-thiouridine 在 磷酸三甲酯 、 Proton Sponge 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 9.17h， 生成 2'-acetylamino-2'-deoxy-2-thiouridine 5'-triphosphate tetrakis(triethylammonium) salt
  参考文献：
  名称：

  Molecular Modeling of the Human P2Y₂ Receptor and Design of a Selective Agonist, 2‘-Amino-2‘-deoxy-2-thiouridine 5‘-Triphosphate

  摘要：

  A rhodopsin-based homology model of the nucleotide-activated human P2Y(2) receptor, including loops, termini, and phospholipids, was optimized with the Monte Carlo multiple minimum conformational search routine. Docked uridine 5'-triphosphate (UTP) formed a nucleobase pi-pi complex with conserved Phe3.32. Selectivity-enhancing 2'-amino-2'-deoxy substitution interacted through pi-hydrogen-bonding with aromatic Phe6.51 and Tyr3.33. A "sequential ligand composition" approach for docking the flexible dinucleotide agonist Up(4)U demonstrated a shift of conserved cationic Arg3.29 from the UTP gamma position to the delta position of Up(4)U and Up(4) ribose. Synthesized nucleotides were tested as agonists at human P2Y receptors expressed in 1321N1 astrocytoma cells. 2'-Amino and 2-thio modifications were synergized to enhance potency and selectivity; compound 8 (EC50 = 8 nM) was 300-fold P2Y(2)-selective versus P2Y(4). 2'-Amine acetylation reduced potency, and trifluoroacetylation produced intermediate potency. 5-Amino nucleobase substitution did not enhance P2Y(2) potency through a predicted hydrophilic interaction possibly because of destabilization of the receptor-favored Northern conformation of ribose. This detailed view of P2Y(2) receptor recognition suggests mutations for model validation.

  DOI：

  10.1021/jm060903o
• 作为产物：
  描述：

  2'-叠氮-2'-脱氧尿苷 在 吡啶 、 硫化氢 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 74.0h， 生成 2'-trifluoroacetylamino-2'-deoxy-2-thiouridine
  参考文献：
  名称：

  Molecular Modeling of the Human P2Y₂ Receptor and Design of a Selective Agonist, 2‘-Amino-2‘-deoxy-2-thiouridine 5‘-Triphosphate

  摘要：

  A rhodopsin-based homology model of the nucleotide-activated human P2Y(2) receptor, including loops, termini, and phospholipids, was optimized with the Monte Carlo multiple minimum conformational search routine. Docked uridine 5'-triphosphate (UTP) formed a nucleobase pi-pi complex with conserved Phe3.32. Selectivity-enhancing 2'-amino-2'-deoxy substitution interacted through pi-hydrogen-bonding with aromatic Phe6.51 and Tyr3.33. A "sequential ligand composition" approach for docking the flexible dinucleotide agonist Up(4)U demonstrated a shift of conserved cationic Arg3.29 from the UTP gamma position to the delta position of Up(4)U and Up(4) ribose. Synthesized nucleotides were tested as agonists at human P2Y receptors expressed in 1321N1 astrocytoma cells. 2'-Amino and 2-thio modifications were synergized to enhance potency and selectivity; compound 8 (EC50 = 8 nM) was 300-fold P2Y(2)-selective versus P2Y(4). 2'-Amine acetylation reduced potency, and trifluoroacetylation produced intermediate potency. 5-Amino nucleobase substitution did not enhance P2Y(2) potency through a predicted hydrophilic interaction possibly because of destabilization of the receptor-favored Northern conformation of ribose. This detailed view of P2Y(2) receptor recognition suggests mutations for model validation.

  DOI：

  10.1021/jm060903o

文献信息

• Molecular Modeling of the Human P2Y₂ Receptor and Design of a Selective Agonist, 2‘-Amino-2‘-deoxy-2-thiouridine 5‘-Triphosphate
  作者：Andrei A. Ivanov、Hyojin Ko、Liesbet Cosyn、Savitri Maddileti、Pedro Besada、Ingrid Fricks、Stefano Costanzi、T. Kendall Harden、Serge Van Calenbergh、Kenneth A. Jacobson

  DOI：10.1021/jm060903o

  日期：2007.3.1

  A rhodopsin-based homology model of the nucleotide-activated human P2Y(2) receptor, including loops, termini, and phospholipids, was optimized with the Monte Carlo multiple minimum conformational search routine. Docked uridine 5'-triphosphate (UTP) formed a nucleobase pi-pi complex with conserved Phe3.32. Selectivity-enhancing 2'-amino-2'-deoxy substitution interacted through pi-hydrogen-bonding with aromatic Phe6.51 and Tyr3.33. A "sequential ligand composition" approach for docking the flexible dinucleotide agonist Up(4)U demonstrated a shift of conserved cationic Arg3.29 from the UTP gamma position to the delta position of Up(4)U and Up(4) ribose. Synthesized nucleotides were tested as agonists at human P2Y receptors expressed in 1321N1 astrocytoma cells. 2'-Amino and 2-thio modifications were synergized to enhance potency and selectivity; compound 8 (EC50 = 8 nM) was 300-fold P2Y(2)-selective versus P2Y(4). 2'-Amine acetylation reduced potency, and trifluoroacetylation produced intermediate potency. 5-Amino nucleobase substitution did not enhance P2Y(2) potency through a predicted hydrophilic interaction possibly because of destabilization of the receptor-favored Northern conformation of ribose. This detailed view of P2Y(2) receptor recognition suggests mutations for model validation.