β-D-N⁴-hydroxycytidine-5'-monophosphate | 4988-54-9

• 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: β-D-N⁴-hydroxycytidine-5'-monophosphate
• 英文别名: N4-OH-CMP；N⁴-hydroxy-[5']cytidylic acid；N⁴-Hydroxycytidin-5'-phosphat；N-Hydroxycytidine 5'-(Dihydrogen Phosphate)；[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(hydroxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl dihydrogen phosphate
• CAS: 4988-54-9
• 化学式: C₉H₁₄N₃O₉P
• 分子量: 339.199
• InChiKey: DYOUVDKCXLKHKY-XVFCMESISA-N

物化性质

• 密度：
  2.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  181
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  cytidine-5'-monophosphate disodium salt 在 Homo sapiens orotidine-5'-monophosphate decarboxylase 、 间氯过氧苯甲酸 作用下， 以 甲醇 为溶剂， 反应 24.25h， 生成 5-OH-CMP 、 β-D-N⁴-hydroxycytidine-5'-monophosphate
  参考文献：
  名称：

  Novel Cytidine-Based Orotidine-5′-Monophosphate Decarboxylase Inhibitors with an Unusual Twist

  摘要：

  Orotidine-5'-monophosphate decarboxylase (ODCase) is an interesting enzyme with an unusual catalytic activity and a potential drug target in Plasmodium falciparum, which causes malaria. ODCase has been shown to exhibit unusual and interesting interactions with a variety of nucleotide ligands. Cytidine-5'-monophosphate (CMP) is a poor ligand of ODCase, and CMP binds to the active site of ODCase with an unusual orientation and conformation. We designed N3- and N4-modified CMP derivatives as novel ligands to ODCase. These novel CMP derivatives and their corresponding nucleosides were evaluated against Plasmodium falciparum ODCase and parasitic cultures, respectively. These derivatives exhibited improved inhibition of the enzyme catalytic activity displayed interesting binding conformations and unusual molecular rearrangements of the ligands. These findings with the modified CMP nucleotides underscored the potential of transformation of poor ligands to ODCase into novel inhibitors of this drug target.

  DOI：

  10.1021/jm301176r

文献信息

• Effects of the 5′‐Triphosphate Metabolites of Ribavirin, Sofosbuvir, Vidarabine, and Molnupiravir on CTP Synthase Catalysis and Filament Formation: Implications for Repurposing Antiviral Agents against SARS‐CoV‐2
  作者：Thomas D. Gillis、Stephen L. Bearne

  DOI：10.1002/cmdc.202200399

  日期：2022.12.5

  pandemics such as COVID-19. Viral replication is sensitive to intracellular CTP levels, yet little is known about the effects of antiviral drug metabolites on CTP synthase activity. We show that the 5′-triphosphates of several antiviral drugs can act as substrates, activators, or inhibitors of the enzyme, underscoring the need to explore such effects.

  重新利用抗病毒药物可能会提供治疗方法来对抗 COVID-19 等流行病。病毒复制对细胞内 CTP 水平敏感，但人们对抗病毒药物代谢物对 CTP 合酶活性的影响知之甚少。我们表明，几种抗病毒药物的 5'-三磷酸盐可以作为酶的底物、激活剂或抑制剂，强调了探索此类作用的必要性。