azane;[(2R,3S,4R,5R)-5-(5-hex-1-ynyl-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate | 1226907-53-4

• 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: azane;[(2R,3S,4R,5R)-5-(5-hex-1-ynyl-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 1226907-53-4
• 化学式: C₁₅H₂₁N₂O₉P*H₃N
• 分子量: 421.344
• InChiKey: QNOWXUMBIRTJIP-XSCHNBKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.03
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  167
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  三正丁胺 、 azane;[(2R,3S,4R,5R)-5-(5-hex-1-ynyl-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  Frontal Affinity Chromatography−Mass Spectrometry Useful for Characterization of New Ligands for GPR17 Receptor

  摘要：

  The application of frontal affinity chromatography mass spectrometry (FAC-MS), along with molecular modeling studies, to the screening of potential drug candidates toward the recently deorphanized G-protein-coupled receptor (GPCR) GPR17 is shown. GPR17 is dually activated by uracil nucleotides and cysteinyl-leukotrienes, and is expressed in organs typically undergoing ischemic damage (i.e., brain, heart and kidney), thus representing a new pharmacological target for acute and chronic neurodegeneration. GPR17 was entrapped on an immobilized artificial membrane (IAM), and this stationary phase was used to screen a library of nucleotide derivatives by FAC-MS to select high affinity ligands. The chromatographic results have been validated with a reference functional assay ([S-35]GTP gamma S binding assay). The receptor nucleotide-binding site was studied by setting up a column where a mutated GPR17 receptor (Arg255Ile) has been immobilized. The chromatographic behavior of the tested nucleotide derivatives together with in silico studies have been used to gain insights into the structure requirement of GPR17 ligands.

  DOI：

  10.1021/jm901691y
• 作为产物：
  描述：

  1-(3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-5-hex-1-ynyl-1H-pyrimidine-2,4-dione 在 磷酸三甲酯 、 三氯氧磷 、 水 、 三乙胺 、 碳酸氢铵 作用下， 以 水 为溶剂， 反应 3.0h， 以45%的产率得到azane;[(2R,3S,4R,5R)-5-(5-hex-1-ynyl-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
  参考文献：
  名称：

  Frontal Affinity Chromatography−Mass Spectrometry Useful for Characterization of New Ligands for GPR17 Receptor

  摘要：

  The application of frontal affinity chromatography mass spectrometry (FAC-MS), along with molecular modeling studies, to the screening of potential drug candidates toward the recently deorphanized G-protein-coupled receptor (GPCR) GPR17 is shown. GPR17 is dually activated by uracil nucleotides and cysteinyl-leukotrienes, and is expressed in organs typically undergoing ischemic damage (i.e., brain, heart and kidney), thus representing a new pharmacological target for acute and chronic neurodegeneration. GPR17 was entrapped on an immobilized artificial membrane (IAM), and this stationary phase was used to screen a library of nucleotide derivatives by FAC-MS to select high affinity ligands. The chromatographic results have been validated with a reference functional assay ([S-35]GTP gamma S binding assay). The receptor nucleotide-binding site was studied by setting up a column where a mutated GPR17 receptor (Arg255Ile) has been immobilized. The chromatographic behavior of the tested nucleotide derivatives together with in silico studies have been used to gain insights into the structure requirement of GPR17 ligands.

  DOI：

  10.1021/jm901691y

文献信息

• Frontal Affinity Chromatography−Mass Spectrometry Useful for Characterization of New Ligands for GPR17 Receptor
  作者：Enrica Calleri、Stefania Ceruti、Gloria Cristalli、Claudia Martini、Caterina Temporini、Chiara Parravicini、Rosaria Volpini、Simona Daniele、Gabriele Caccialanza、Davide Lecca、Catia Lambertucci、Maria Letizia Trincavelli、Gabriella Marucci、Irving W. Wainer、Graziella Ranghino、Piercarlo Fantucci、Maria P. Abbracchio、Gabriella Massolini

  DOI：10.1021/jm901691y

  日期：2010.5.13

  The application of frontal affinity chromatography mass spectrometry (FAC-MS), along with molecular modeling studies, to the screening of potential drug candidates toward the recently deorphanized G-protein-coupled receptor (GPCR) GPR17 is shown. GPR17 is dually activated by uracil nucleotides and cysteinyl-leukotrienes, and is expressed in organs typically undergoing ischemic damage (i.e., brain, heart and kidney), thus representing a new pharmacological target for acute and chronic neurodegeneration. GPR17 was entrapped on an immobilized artificial membrane (IAM), and this stationary phase was used to screen a library of nucleotide derivatives by FAC-MS to select high affinity ligands. The chromatographic results have been validated with a reference functional assay ([S-35]GTP gamma S binding assay). The receptor nucleotide-binding site was studied by setting up a column where a mutated GPR17 receptor (Arg255Ile) has been immobilized. The chromatographic behavior of the tested nucleotide derivatives together with in silico studies have been used to gain insights into the structure requirement of GPR17 ligands.