Up3-[1]glucose | 1242162-16-8

• 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: Up3-[1]glucose
• 英文别名: P1-Uridine 5''-P3-[1]Glucose-1''-Triphosphate TriethylammoniumSalt；[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [hydroxy-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphosphoryl] hydrogen phosphate
• CAS: 1242162-16-8
• 化学式: C₁₅H₂₅N₂O₂₀P₃
• 分子量: 646.286
• InChiKey: HACYEUYJNVLBRJ-JZMIEXBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7.4
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  338
• 氢给体数：
  10
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  Up3-[1]glucose 、 乙酸–三乙胺 在 Luna RP-C₁₈⁽²⁾ column 作用下， 以 乙腈 为溶剂， 以1.8 mg的产率得到P1-uridine 5-P3-[1]-glucose-1-triphosphate triethylammonium salt
  参考文献：
  名称：

  Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y₆ Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5′-Triphosphate γ-Ester Modifications

  摘要：

  The P2Y(6) receptor is a cytoprotective G-protein-coupled receptor (GPCR) activated by UDP (EC50 = 0.30 mu M). We compared and combined modifications to enhance P2Y(6) receptor agonist selectivity, including ribose ring constraint, 5-iodo and 4-alkyloxyimino modifications, and phosphate modifications such as alpha,beta-methylene and extension of the terminal phosphate group into gamma-esters of UTP analogues. The conformationally constrained (S)-methanocarba-UDP is a full agonist (EC50 = 0.042 mu M). 4-Methoxyimino modification of pyrimidine enhanced P2Y(6), preserved P2Y(2) and P2Y(4), and abolished P2Y(14) receptor potency, in the appropriate nucleotide. N-4-Benzyloxy-CDP (15, MRS2964) and N-4-methoxy-Cp3U Cp3U (12, MRS2957) were potent, selective P2Y(6) receptor agonists (EC50 of 0.026 and 0.012 mu M, respectively). A hydrophobic binding region near the nucleobase was explored with receptor modeling and docking. UTP-gamma-aryl and cycloalkyl phosphoesters displayed only intermediate P2Y(6) receptor potency but had enhanced stability in acid and cell membranes. UTP-glucose was inactive, but its (S)-methanocarba analogue and N-4-methoxycytidine 5'-triphospho-gamma-[1]glucose were active (EC50 of 2.47 and 0.18 mu M, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y(6) receptor agonists may be enhanced by modest structural changes.

  DOI：

  10.1021/jm100287t
• 作为产物：
  描述：

  uridine 5'-diphosphate, tributylammonium 、 α-D-glucose-1-phosphate tributylammonium salt 在 N,N'-二异丙基碳二亚胺 、 magnesium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 Up3-[1]glucose
  参考文献：
  名称：

  Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y₆ Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5′-Triphosphate γ-Ester Modifications

  摘要：

  The P2Y(6) receptor is a cytoprotective G-protein-coupled receptor (GPCR) activated by UDP (EC50 = 0.30 mu M). We compared and combined modifications to enhance P2Y(6) receptor agonist selectivity, including ribose ring constraint, 5-iodo and 4-alkyloxyimino modifications, and phosphate modifications such as alpha,beta-methylene and extension of the terminal phosphate group into gamma-esters of UTP analogues. The conformationally constrained (S)-methanocarba-UDP is a full agonist (EC50 = 0.042 mu M). 4-Methoxyimino modification of pyrimidine enhanced P2Y(6), preserved P2Y(2) and P2Y(4), and abolished P2Y(14) receptor potency, in the appropriate nucleotide. N-4-Benzyloxy-CDP (15, MRS2964) and N-4-methoxy-Cp3U Cp3U (12, MRS2957) were potent, selective P2Y(6) receptor agonists (EC50 of 0.026 and 0.012 mu M, respectively). A hydrophobic binding region near the nucleobase was explored with receptor modeling and docking. UTP-gamma-aryl and cycloalkyl phosphoesters displayed only intermediate P2Y(6) receptor potency but had enhanced stability in acid and cell membranes. UTP-glucose was inactive, but its (S)-methanocarba analogue and N-4-methoxycytidine 5'-triphospho-gamma-[1]glucose were active (EC50 of 2.47 and 0.18 mu M, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y(6) receptor agonists may be enhanced by modest structural changes.

  DOI：

  10.1021/jm100287t

文献信息

• Polyphosphate-containing bisubstrate analogues as inhibitors of a bacterial cell wall thymidylyltransferase
  作者：Deborah A. Smithen、Stephanie M. Forget、Nicole E. McCormick、Raymond T. Syvitski、David L. Jakeman

  DOI：10.1039/c4ob02583k

  日期：——

  The first synthesis and evaluation of bisubstrate analogues with a thymidylyltransferase is reported. WaterLOGSY NMR and kinetic analyses provide insight into bisubstrate analogue binding.

  报道了第一次合成和评价具有胸苷酸转移酶的双底物类似物。WaterLOGSY NMR和动力学分析提供了关于双底物类似物结合的见解。
• Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y₆ Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5′-Triphosphate γ-Ester Modifications
  作者：Hiroshi Maruoka、Matthew O. Barrett、Hyojin Ko、Dilip K. Tosh、Artem Melman、Lauren E. Burianek、Ramachandran Balasubramanian、Barkin Berk、Stefano Costanzi、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm100287t

  日期：2010.6.10

  The P2Y(6) receptor is a cytoprotective G-protein-coupled receptor (GPCR) activated by UDP (EC50 = 0.30 mu M). We compared and combined modifications to enhance P2Y(6) receptor agonist selectivity, including ribose ring constraint, 5-iodo and 4-alkyloxyimino modifications, and phosphate modifications such as alpha,beta-methylene and extension of the terminal phosphate group into gamma-esters of UTP analogues. The conformationally constrained (S)-methanocarba-UDP is a full agonist (EC50 = 0.042 mu M). 4-Methoxyimino modification of pyrimidine enhanced P2Y(6), preserved P2Y(2) and P2Y(4), and abolished P2Y(14) receptor potency, in the appropriate nucleotide. N-4-Benzyloxy-CDP (15, MRS2964) and N-4-methoxy-Cp3U Cp3U (12, MRS2957) were potent, selective P2Y(6) receptor agonists (EC50 of 0.026 and 0.012 mu M, respectively). A hydrophobic binding region near the nucleobase was explored with receptor modeling and docking. UTP-gamma-aryl and cycloalkyl phosphoesters displayed only intermediate P2Y(6) receptor potency but had enhanced stability in acid and cell membranes. UTP-glucose was inactive, but its (S)-methanocarba analogue and N-4-methoxycytidine 5'-triphospho-gamma-[1]glucose were active (EC50 of 2.47 and 0.18 mu M, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y(6) receptor agonists may be enhanced by modest structural changes.