9-[3'-O-tert-butyldimethylsilyl-5',6'-dideoxy-6'-(hydroxyphosphinyl)-2'-C-methyl-β-D-ribohexofuranosyl]adenine | 851085-38-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 9-[3'-O-tert-butyldimethylsilyl-5',6'-dideoxy-6'-(hydroxyphosphinyl)-2'-C-methyl-β-D-ribohexofuranosyl]adenine
• 英文别名: 2-[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxy-4-methyloxolan-2-yl]ethylphosphonic acid
• CAS: 851085-38-6
• 化学式: C₁₈H₃₂N₅O₆PSi
• 分子量: 473.541
• InChiKey: SPEIYBJGZHLSBD-MAAOGQSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  9-[3'-O-tert-butyldimethylsilyl-5',6'-dideoxy-6'-(hydroxyphosphinyl)-2'-C-methyl-β-D-ribohexofuranosyl]adenine 在 吡啶 、 四丁基氟化铵 、 苯甲基-2-磺酰三硝基三氮唑 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 34.0h， 生成 2,2-Dimethyl-thiopropionic acid S-(2-{{2-[(2R,3R,4R,5R)-5-(6-amino-purin-9-yl)-3,4-dihydroxy-4-methyl-tetrahydro-furan-2-yl]-ethyl}-[2-(2,2-dimethyl-propionylsulfanyl)-ethoxy]-phosphinoyloxy}-ethyl) ester
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Adenosine 5‘-Phosphonate Analogues as Chain Terminators against Hepatitis C Virus

  摘要：

  A series of adenosine 5'-phosphonate analogues were designed to mimic naturally occurring adenosine monophosphate. These compounds (1-5) were synthesized and evaluated in a cellular hepatitis C virus (HCV) replication assay. To improve cellular permeability and enhance the anti-HCV activity of these phosphonates, a bis(S-acyl-2-thioethyl) prodrug for compound 5 was prepared, and its cellular activity was determined. To elucidate the mechanism of action of these novel adenosine phosphonates, their diphosphate derivatives (1a-5a) were synthesized. Further nucleotide incorporation assays by HCV NS5B RNA-dependent RNA polymerase revealed that 2a and 3a can serve as chain terminators, whereas compounds 1a, 4a, and 5a are competitive inhibitors with ATP. Additional steady-state kinetic analysis determined the incorporation efficiency of 2a and 3a as well as the inhibition constants for 1a, 4a, and 5a. The structure -activity relationships among these compounds were analyzed, and the implication for nucleoside phosphonate drug design was discussed.

  DOI：

  10.1021/jm049029u
• 作为产物：
  描述：

  {2-[(2R,3R,4R,5R)-5-(6-Benzoylamino-purin-9-yl)-3,4-dihydroxy-4-methyl-tetrahydro-furan-2-yl]-ethyl}-phosphonic acid dibenzyl ester 在 palladium on activated charcoal 咪唑 、 氨 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 9-[3'-O-tert-butyldimethylsilyl-5',6'-dideoxy-6'-(hydroxyphosphinyl)-2'-C-methyl-β-D-ribohexofuranosyl]adenine
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Adenosine 5‘-Phosphonate Analogues as Chain Terminators against Hepatitis C Virus

  摘要：

  A series of adenosine 5'-phosphonate analogues were designed to mimic naturally occurring adenosine monophosphate. These compounds (1-5) were synthesized and evaluated in a cellular hepatitis C virus (HCV) replication assay. To improve cellular permeability and enhance the anti-HCV activity of these phosphonates, a bis(S-acyl-2-thioethyl) prodrug for compound 5 was prepared, and its cellular activity was determined. To elucidate the mechanism of action of these novel adenosine phosphonates, their diphosphate derivatives (1a-5a) were synthesized. Further nucleotide incorporation assays by HCV NS5B RNA-dependent RNA polymerase revealed that 2a and 3a can serve as chain terminators, whereas compounds 1a, 4a, and 5a are competitive inhibitors with ATP. Additional steady-state kinetic analysis determined the incorporation efficiency of 2a and 3a as well as the inhibition constants for 1a, 4a, and 5a. The structure -activity relationships among these compounds were analyzed, and the implication for nucleoside phosphonate drug design was discussed.

  DOI：

  10.1021/jm049029u