α-(4-azidophenyl)-1,N⁶-etheno-2'-deoxyadenosine 5'-monophosphate | 851034-22-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: α-(4-azidophenyl)-1,N⁶-etheno-2'-deoxyadenosine 5'-monophosphate
• 英文别名: [(2R,3S,5R)-5-[7-(4-azidophenyl)imidazo[2,1-f]purin-3-yl]-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 851034-22-5
• 化学式: C₁₈H₁₇N₈O₆P
• 分子量: 472.357
• InChiKey: DOYZPCJKRUMLMJ-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  α-(4-azidophenyl)-1,N⁶-etheno-2'-deoxyadenosine 5'-monophosphate 在 三正丁胺 、 phenylphosphorochloridate 、 吡啶 、 tri-n-butylamine pyrophosphate 作用下， 以 1,4-二氧六环 为溶剂， 以50%的产率得到α-(4-azidophenyl)-1,N⁶-etheno-2'-deoxyadenosine 5'-triphosphate
  参考文献：
  名称：

  Side‐Chain Conformational Restriction in Template‐Competitive Inhibitors of E. coliDNA Polymerase I Klenow Fragment: Synthesis, Structural Characterization and Inhibition Activity

  摘要：

  Nucleotide triphosphate alpha-(4-azidophenyl)-1,N-6-etheno-dATP 3 and its monophosphate 3m were synthesized by condensation of 2-halo-2-(4-azidophenyl)acetaldehyes with dATP and dAMP, respectively. Structure analysis shows that the azidophenyl side chain is attached to the alpha-position of the etheno ring (i.e., the carbon attached to N1 of the purine), and conformation calculations show minima in the etheno-phenyl bond rotation at 50 and 130degrees where the bulk of the phenyl ring projects out from the plane of the etheno group. Like DNA Pol inhibitor 2-(4-azidophenacyl)thio-2'-deoxyadenosine 5'-triphosphate 1, nucleotide 3 is a template-competitive DNA polymerase inhibitor (TCPI), with a competitive Ki for Pol I KF of 3.41 muM, but has only weak activity as an HIV RT inhibitor relative to the template-competitive reverse transcriptase inhibitor 2-(4-azidophenacyl)thio-1,N-6-etheno-2'-deoxyadenosine 5'-triphosphate 2. Additionally, 3 photoinactivates KF in a time-dependent manner, confirming the kinetic data that 3 binds to the free form of KF. The TCPI activity of 3 provides evidence for an extended side chain conformational preference in the combined substrate polymerase inhibitors.

  DOI：

  10.1081/ncn-200034042
• 作为产物：
  描述：

  2-(4-azidophenyl)acetaldehyde 在 次氯酸叔丁酯 、 sodium acetate 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 25.0h， 生成 α-(4-azidophenyl)-1,N⁶-etheno-2'-deoxyadenosine 5'-monophosphate
  参考文献：
  名称：

  Side‐Chain Conformational Restriction in Template‐Competitive Inhibitors of E. coliDNA Polymerase I Klenow Fragment: Synthesis, Structural Characterization and Inhibition Activity

  摘要：

  Nucleotide triphosphate alpha-(4-azidophenyl)-1,N-6-etheno-dATP 3 and its monophosphate 3m were synthesized by condensation of 2-halo-2-(4-azidophenyl)acetaldehyes with dATP and dAMP, respectively. Structure analysis shows that the azidophenyl side chain is attached to the alpha-position of the etheno ring (i.e., the carbon attached to N1 of the purine), and conformation calculations show minima in the etheno-phenyl bond rotation at 50 and 130degrees where the bulk of the phenyl ring projects out from the plane of the etheno group. Like DNA Pol inhibitor 2-(4-azidophenacyl)thio-2'-deoxyadenosine 5'-triphosphate 1, nucleotide 3 is a template-competitive DNA polymerase inhibitor (TCPI), with a competitive Ki for Pol I KF of 3.41 muM, but has only weak activity as an HIV RT inhibitor relative to the template-competitive reverse transcriptase inhibitor 2-(4-azidophenacyl)thio-1,N-6-etheno-2'-deoxyadenosine 5'-triphosphate 2. Additionally, 3 photoinactivates KF in a time-dependent manner, confirming the kinetic data that 3 binds to the free form of KF. The TCPI activity of 3 provides evidence for an extended side chain conformational preference in the combined substrate polymerase inhibitors.

  DOI：

  10.1081/ncn-200034042