[(1S,2S,3S,4R)-4-(6-aminopurin-9-yl)-2,3-dihydroxycyclopentyl]oxymethylphosphonic acid | 152772-75-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: [(1S,2S,3S,4R)-4-(6-aminopurin-9-yl)-2,3-dihydroxycyclopentyl]oxymethylphosphonic acid
• CAS: 152772-75-3
• 化学式: C₁₁H₁₆N₅O₆P
• 分子量: 345.252
• InChiKey: DGOIRXAQGISTLH-CRYJXSNHSA-N

物化性质

• 沸点：
  740.7±70.0 °C(predicted)
• 密度：
  2.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  177
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [(1S,2S,3S,4R)-4-(6-aminopurin-9-yl)-2,3-dihydroxycyclopentyl]oxymethylphosphonic acid 在 N,N'-羰基二咪唑 、 三丁基焦磷酸铵 作用下， 以 N,N-二甲基甲酰胺 、 甲醇 为溶剂， 以47%的产率得到(1R,2R,3S,4S)-9-[2,3-dihydroxy-4-[(hydroxylpyrophosphoroxy)phosphonomethoxy]-cyclopent-1-yl]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：

  6-噁双环[3.1.0]-3-己烯 在 四氧化锇 、 四(三苯基膦)钯 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 [(1S,2S,3S,4R)-4-(6-aminopurin-9-yl)-2,3-dihydroxycyclopentyl]oxymethylphosphonic acid
  参考文献：
  名称：

  Merlo, Valeria; Reece, Fiona J.; Roberts, Stanley M., Journal of the Chemical Society. Perkin transactions I, 1993, # 15, p. 1717 - 1718

  摘要：

  DOI：

文献信息

• Merlo, Valeria; Reece, Fiona J.; Roberts, Stanley M., Journal of the Chemical Society. Perkin transactions I, 1993, # 15, p. 1717 - 1718
  作者：Merlo, Valeria、Reece, Fiona J.、Roberts, Stanley M.、Gredson, Mike、Storer, Richard

  DOI：——

  日期：——
• 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.