diisopropyl ({(1R)-2-[2-amino-6-(formylamino)-9H-purin-9-yl]-1-methylethyl}oxy)methylphosphonate | 1425688-69-2

• 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: diisopropyl ({(1R)-2-[2-amino-6-(formylamino)-9H-purin-9-yl]-1-methylethyl}oxy)methylphosphonate
• 英文别名: N-[2-amino-9-[(2R)-2-[[oxido-di(propan-2-yloxy)phosphaniumyl]methoxy]propyl]purin-6-yl]formamide
• CAS: 1425688-69-2
• 化学式: C₁₆H₂₇N₆O₅P
• 分子量: 414.401
• InChiKey: LZRVZVSLWWWRSN-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (二异丙氧基磷酰)甲基对甲苯磺酸酯 、 N,N-二甲基甲酰胺 、 (R)-9-(2-hydroxypropyl)-2,6-diaminopurine 在 sodium hydride 作用下， 反应 24.0h， 以9 g的产率得到(R)-9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine diisopropyl ester
  参考文献：
  名称：

  9-[2-(R)-(Phosphonomethoxy)propyl]-2,6-diaminopurine (R)-PMPDAP and its prodrugs: Optimized preparation, including identification of by-products formed, and antiviral evaluation in vitro

  摘要：

  New large-scale synthetic approach to antiretroviral agent 9-[2-(R)-(phosphonomethoxy) propyl]-2,6-diaminopurine, (R)-PMPDAP, was developed. Reaction of (R)-propanediol carbonate with 2,6-diaminopurine afforded exclusively (R)-9-(2-hydroxypropyl)-2,6-diaminopurine which was subsequently used for introduction of a phosphonomethyl residue using TsOCH2P(O)(OiPr)(2) or BrCH2P(O)(OiPr)(2) followed by deprotection of ester groups. All minor ingredients and by-products formed during the process were identified and further studied. The final product was obtained in high yield and its high enantiomeric purity (>99%) was confirmed by chiral capillary electrophoretic analysis using beta-cyclodextrin as a chiral selector. Antiretroviral activity data of (R)-PMPDAP and its diverse prodrugs against HIV and FIV were investigated. Akin to (R)-PMPDAP, both prodrugs inhibit FIV replication in a selective manner. Compared to the parent molecule, the amidate prodrug was 10-fold less active against FIV in cell culture, whereas the alkoxyalkyl ester prodrug was 200-fold more potent in inhibiting FIV replication in vitro. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.044