{2-[(2S,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]ethyl}phosphonic acid | 1363739-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: {2-[(2S,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]ethyl}phosphonic acid
• 英文别名: 1-[2,5,6-trideoxy-6-(dihydroxyphosphinyl)-α-D-hexofuranosyl]uracil
• CAS: 1363739-83-6
• 化学式: C₁₀H₁₅N₂O₇P
• 分子量: 306.212
• InChiKey: RJNCOKMSVJALCN-OOZYFLPDSA-N

物化性质

• 密度：
  1.637±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.25
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  141.85
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  dimethyl [(E)-2-[(2R,5R)-3-[(tert-butyldimethylsilyl)oxy]-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-2-yl]ethenyl]phosphonate 在 三甲基溴硅烷 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 乙腈 为溶剂， 60.0 ℃ 、101.33 kPa 条件下， 反应 1.12h， 生成 {2-[(2S,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]ethyl}phosphonic acid 、 {2‐[(2R,5R)‐5‐(2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐1‐yl)‐3‐hydroxyoxolan‐2‐yl]ethyl}phosphonic acid
  参考文献：
  名称：

  Small Molecule Inhibition of SAMHD1 dNTPase by Tetramer Destabilization

  摘要：

  SAMHD1 is a GTP-activated nonspecific dNTP triphosphohydrolase that depletes dNTP pools in resting CD4+ T cells and macrophages and effectively restricts infection by HIV-1. We have designed a nonsubstrate dUTP analogue with a methylene bridge connecting the a phosphate and 5' carbon that potently inhibits SAMHD1. Although pppCH(2)dU shows apparent competitive inhibition, it acts by a surprising allosteric mechanism that destabilizes active enzyme tetramer.

  DOI：

  10.1021/ja5035717

文献信息

• Synthesis of 5-Substituted 2′-Deoxyuridine-5′- Phosphonate Analogues and Evaluation of their Antiviral Activity
  作者：Sara Van Poecke、Davy Sinnaeve、José C. Martins、Jan Balzarini、Serge Van Calenbergh

  DOI：10.1080/15257770.2012.654876

  日期：2012.3

  A small series of 5-(hetero)aryl-modified nucleoside phosphonates was synthesized via an 8-step procedure including a Wittig reaction and Suzuki–Miyaura coupling. An unanticipated anomerization during phosphonate deprotection allowed us to isolate both anomers of the 5-substituted 2′-deoxy-uridine phosphonates and assess their antiviral activity against a broad panel of viruses.

  通过5-步骤（包括Wittig反应和Suzuki-Miyaura偶联）的一小步步骤，合成了少量的5-（杂）芳基修饰的核苷膦酸酯。膦酸酯去保护过程中出乎意料的异化反应使我们能够分离5位取代的2'-脱氧尿苷膦酸酯的两种异构体，并评估它们对多种病毒的抗病毒活性。