(S)-N6-cyclopropyl-2,6-diamino-9-[3-fluoro-2-(phosphonomethoxy)propyl]purine | 1305351-79-4

• 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: (S)-N6-cyclopropyl-2,6-diamino-9-[3-fluoro-2-(phosphonomethoxy)propyl]purine
• 英文别名: [(1S)-1-[[2-amino-6-(cyclopropylamino)purin-9-yl]methyl]-2-fluoro-ethoxy]methylphosphonic acid；[(2S)-1-[2-amino-6-(cyclopropylamino)purin-9-yl]-3-fluoropropan-2-yl]oxymethylphosphonic acid
• CAS: 1305351-79-4
• 化学式: C₁₂H₁₈FN₆O₄P
• 分子量: 360.285
• InChiKey: UFZJAPCFBPHQNK-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-N6-cyclopropyl-2,6-diamino-9-[3-fluoro-2-(phosphonomethoxy)propyl]purine 在 吡啶 、 2,2'-二硫二吡啶 、 三乙胺 、 三苯基膦 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 3.0h， 生成 (2S,2'S)-diethyl 2,2'-[{[({(S)-1-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-3-fluoropropan-2-yl}oxy)methyl]phosphoryl}bis(azanediyl)]dipropanoate
  参考文献：
  名称：

  一种新型高效的一锅法合成无环核苷膦酸酯对称的二酰胺（双酰胺）前体药物及其生物学活性

  摘要：

  报道了一种从游离膦酸或膦酸酯二酯开始一锅合成无环核苷膦酸酯的二酰胺（双酰胺）前体药物的新颖有效的方法。膦酸酯二酯通过其双（三甲基甲硅烷基）酯的方法非常方便，消除了膦酸的分离和繁琐的纯化，并以极佳的收率（83-98％）和纯度提供了相应的双氨基酸酯。该方法已应用于有效的抗癌药GS-9219以及其他具有生物活性的膦酸的对称双氨基酸盐的合成。讨论了该化合物的抗HIV，抗增殖和免疫调节活性，包括双氨基酸盐前药14和17 在亚微摩尔浓度下表现出抗HIV活性，且细胞毒性最小。

  DOI：

  10.1016/j.ejmech.2011.05.040
• 作为产物：
  描述：

  在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 以221 mg的产率得到(S)-N6-cyclopropyl-2,6-diamino-9-[3-fluoro-2-(phosphonomethoxy)propyl]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

• A novel and efficient one-pot synthesis of symmetrical diamide (bis-amidate) prodrugs of acyclic nucleoside phosphonates and evaluation of their biological activities
  作者：Petr Jansa、Ondřej Baszczyňski、Martin Dračínský、Ivan Votruba、Zdeněk Zídek、Gina Bahador、George Stepan、Tomas Cihlar、Richard Mackman、Antonín Holý、Zlatko Janeba

  DOI：10.1016/j.ejmech.2011.05.040

  日期：2011.9

  bis-amidates in excellent yields (83–98%) and purity. The methodology has been applied to the synthesis of the potent anticancer agent GS-9219, and symmetrical bis-amidates of other biologically active phosphonic acids. Anti-HIV, antiproliferative, and immunomodulatory activities of the compounds are discussed including the bis-amidate prodrugs 14 and 17 that exhibited anti-HIV activity at submicromolar

  报道了一种从游离膦酸或膦酸酯二酯开始一锅合成无环核苷膦酸酯的二酰胺（双酰胺）前体药物的新颖有效的方法。膦酸酯二酯通过其双（三甲基甲硅烷基）酯的方法非常方便，消除了膦酸的分离和繁琐的纯化，并以极佳的收率（83-98％）和纯度提供了相应的双氨基酸酯。该方法已应用于有效的抗癌药GS-9219以及其他具有生物活性的膦酸的对称双氨基酸盐的合成。讨论了该化合物的抗HIV，抗增殖和免疫调节活性，包括双氨基酸盐前药14和17 在亚微摩尔浓度下表现出抗HIV活性，且细胞毒性最小。
• Synthesis and antiviral activity of N9-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N6-substituted adenines and 2,6-diaminopurines
  作者：Ondřej Baszczyňski、Petr Jansa、Martin Dračínský、Blanka Klepetářová、Antonín Holý、Ivan Votruba、Erik de Clercq、Jan Balzarini、Zlatko Janeba

  DOI：10.1016/j.bmc.2011.02.050

  日期：2011.4

  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.