N⁶-dibenzoyl-9H-(3'-O-benzoyl-2'-C-methyl-β-D-ribofuranosyl)adenine | 851085-34-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N⁶-dibenzoyl-9H-(3'-O-benzoyl-2'-C-methyl-β-D-ribofuranosyl)adenine
• 英文别名: [(2R,3R,4R,5R)-5-[6-(dibenzoylamino)purin-9-yl]-4-hydroxy-2-(hydroxymethyl)-4-methyloxolan-3-yl] benzoate
• CAS: 851085-34-2
• 化学式: C₃₂H₂₇N₅O₇
• 分子量: 593.596
• InChiKey: YPJNZUZEVHFITK-KHWZNAFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  157
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N⁶-dibenzoyl-9H-(3'-O-benzoyl-2'-C-methyl-β-D-ribofuranosyl)adenine 在 palladium on activated charcoal 吡啶 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 20.0 ℃ 、206.84 kPa 条件下， 生成 N⁶-benzoyl-9-[3'-O-benzoyl-5',6'-dideoxy-6'-(diphenoxyphosphinyl)-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
• 作为产物：
  描述：

  2’-C-甲基腺苷 在 吡啶 、 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.0h， 生成 N⁶-dibenzoyl-9H-(3'-O-benzoyl-2'-C-methyl-β-D-ribofuranosyl)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

文献信息

• Design, Synthesis, and Antiviral Activity of Adenosine 5‘-Phosphonate Analogues as Chain Terminators against Hepatitis C Virus
  作者：Yung-hyo Koh、Jae Hoon Shim、Jim Zhen Wu、Weidong Zhong、Zhi Hong、Jean-Luc Girardet

  DOI：10.1021/jm049029u

  日期：2005.4.1

  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.