(R)-1-{2-amino-6-[((R)-2-hydroxypropyl)amino]-9H-purin-9-yl}propan-2-ol | 1425688-66-9

• 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)-1-{2-amino-6-[((R)-2-hydroxypropyl)amino]-9H-purin-9-yl}propan-2-ol
• 英文别名: (2R)-1-[[2-amino-9-[(2R)-2-hydroxypropyl]purin-6-yl]amino]propan-2-ol
• CAS: 1425688-66-9
• 化学式: C₁₁H₁₈N₆O₂
• 分子量: 266.303
• InChiKey: FRHBKPUYUFMTJV-RNFRBKRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N,N-二甲基甲酰胺 、 2,6-二氨基嘌呤 、 R-碳酸丙烯酯 在 sodium hydroxide 作用下， 反应 24.0h， 以5%的产率得到(R)-N-(6-amino-9-(2-hydroxypropyl)-9H-purin-2-yl)formamide
  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

文献信息

• 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
  作者：Marcela Krečmerová、Petr Jansa、Martin Dračínský、Petra Sázelová、Václav Kašička、Johan Neyts、Joeri Auwerx、Eleonóra Kiss、Nesya Goris、George Stepan、Zlatko Janeba

  DOI：10.1016/j.bmc.2012.12.044

  日期：2013.3

  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.