(R)-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}purine | 1305351-58-9

• 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)-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}purine
• CAS: 1305351-58-9
• 化学式: C₁₅H₂₃ClFN₄O₄P
• 分子量: 408.797
• InChiKey: CXPMBOFJVVSMKY-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  26.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  88.36
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (R)-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}purine 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 生成 (R)-N6-cyclopropyl-9-[3-fluoro-2-(phosphonomethoxy)-propyl]adenine
  参考文献：
  名称：

  Synthesis and antiviral activity of N9-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N6-substituted adenines and 2,6-diaminopurines

  摘要：

  An efficient method for the synthesis of N-9-[3-fluoro-2-(phosphonomethoxy) propyl] (FPMP) derivatives of purine bases has been developed. Both (R)- and (S)-enantiomers of the N-6-substituted FPMP derivatives of adenine and 2,6-diaminopurine were prepared and their anti-human immunodeficiency virus (HIV) and anti-Moloney murine sarcoma virus (MSV) activity was evaluated. Whereas none of the 6-substituted FPMPA derivatives showed any antiviral activity, several FPMPDAP derivatives had a moderate antiretroviral activity. Moreover, the data obtained from the study of the substrate activity of the active derivatives towards N-6-methyl-AMP aminohydrolase support the notion that the studied N-6-substituted FPMPDAP derivatives act as prodrugs of the antiretroviral FPMPG analogues. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.050
• 作为产物：
  描述：

  diisopropyl (R)-{[(1-fluoro-3-hydroxypropan-2-yl)oxy]methyl}phosphonate 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 11.0h， 生成 (R)-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}purine
  参考文献：
  名称：

  Synthesis and antiviral activity of N9-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N6-substituted adenines and 2,6-diaminopurines

  摘要：

  An efficient method for the synthesis of N-9-[3-fluoro-2-(phosphonomethoxy) propyl] (FPMP) derivatives of purine bases has been developed. Both (R)- and (S)-enantiomers of the N-6-substituted FPMP derivatives of adenine and 2,6-diaminopurine were prepared and their anti-human immunodeficiency virus (HIV) and anti-Moloney murine sarcoma virus (MSV) activity was evaluated. Whereas none of the 6-substituted FPMPA derivatives showed any antiviral activity, several FPMPDAP derivatives had a moderate antiretroviral activity. Moreover, the data obtained from the study of the substrate activity of the active derivatives towards N-6-methyl-AMP aminohydrolase support the notion that the studied N-6-substituted FPMPDAP derivatives act as prodrugs of the antiretroviral FPMPG analogues. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.050

文献信息

• The effect of novel [3-fluoro-(2-phosphonoethoxy)propyl]purines on the inhibition of Plasmodium falciparum, Plasmodium vivax and human hypoxanthine–guanine–(xanthine) phosphoribosyltransferases
  作者：Ondřej Baszczyňski、Dana Hocková、Zlatko Janeba、Antonín Holý、Petr Jansa、Martin Dračínský、Dianne T. Keough、Luke W. Guddat

  DOI：10.1016/j.ejmech.2013.06.032

  日期：2013.9

  Protozoan parasites from the Plasmodiidae family are the causative agents of malaria. Inhibition of hypoxanthine guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT) has been suggested as a target for development of new anti-malarial therapeutics. Acyclic nucleoside phosphonates (ANPs) are potent and selective inhibitors of plasmodial HG(X)PRTs. A new series of ANPs, based on the chemical structure and inhibitory activity of three ANPs, 2-(phosphonoethoxy)ethyl with either guanine or hypoxanthine as the base (PEEG and PEEHx) and 3-hydroxy-2-(phosphonomethoxy)propyl with guanine as the base (HPMPG), were prepared. These compounds are stereoisomers of 3-fluoro-(2-phosphonoethoxy)propyl (FPEPs) and 3-fluoro-(2-phosphonomethoxy)propyl (FPMPs) analogues. Both the (R)- and (S)-isomers of these fluorinated derivatives have higher K-i values (by 10- to 1000-fold) for human HGPRT and Plasmodium falciparum HGXPRT than the non-fluorinated ANPs. Possible explanations for these changes in affinity are proposed based on docking studies using the known crystal structures of human HGPRT in complex with PEEG. (C) 2013 Elsevier Masson SAS. All rights reserved.