(R)-5-amino-1-<2-(phosphonomethoxy)propyl>-1H-imidazo<4,5-d>pyrimidin-7-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (R)-5-amino-1-<2-(phosphonomethoxy)propyl>-1H-imidazo<4,5-d>pyrimidin-7-one
• 英文别名: [(2R)-1-(2-amino-6-oxo-1H-purin-7-yl)propan-2-yl]oxymethylphosphonic acid
• 化学式: C₉H₁₄N₅O₅P
• 分子量: 303.214
• InChiKey: VUKWPIJNOBEDMT-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (R)-5-amino-1-<2-<(diisopropylphosphono)methoxy>propyl>-1H-imidazo<4,5-d>pyrimidin-7-one 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以78%的产率得到(R)-5-amino-1-<2-(phosphonomethoxy)propyl>-1H-imidazo<4,5-d>pyrimidin-7-one
  参考文献：
  名称：

  Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines

  摘要：

  (R)- And (S)-8-aza-9-[2-(phosphonomethoxy)propyl] [(R)- and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9-[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)2-O-[(diisopropylphosphono)methyl]-1-O-(followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)-[2-[(diisopropylphosphono)methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC(50) values of 12 and 4.5 mu M, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.

  DOI：

  10.1021/jm00020a015

文献信息

• Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines
  作者：Palmarisa Franchetti、Ghassan Abu Sheikha、Loredana Cappellacci、Mario Grifantini、Antonella De Montis、Giovanna Piras、Anna Giulia Loi、Paolo La Colla

  DOI：10.1021/jm00020a015

  日期：1995.9

  (R)- And (S)-8-aza-9-[2-(phosphonomethoxy)propyl] [(R)- and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9-[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)2-O-[(diisopropylphosphono)methyl]-1-O-(followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)-[2-[(diisopropylphosphono)methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC(50) values of 12 and 4.5 mu M, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.