2-[[(2S,5R)-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-[2-(2,2-dimethylpropanoyloxy)ethylsulfanyl]phosphoryl]sulfanylethyl 2,2-dimethylpropanoate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-[[(2S,5R)-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-[2-(2,2-dimethylpropanoyloxy)ethylsulfanyl]phosphoryl]sulfanylethyl 2,2-dimethylpropanoate
• 化学式: C₂₄H₃₈N₅O₇PS₂
• 分子量: 603.701
• InChiKey: FFOQETAVIOFVNK-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  39
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  208
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  2',3'-双脱氧腺苷 在 四氮唑 、 叔丁基过氧化氢 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 2-[[(2S,5R)-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-[2-(2,2-dimethylpropanoyloxy)ethylsulfanyl]phosphoryl]sulfanylethyl 2,2-dimethylpropanoate
  参考文献：
  名称：

  The Pronucleotide Approach. I. Synthesis, Anti-HIV Activity and Preliminary Stability Studies of MononucleosideS,S′-Bis(O-acyl-2-oxyethyl) Phosphorodithiolates

  摘要：

  The synthesis, in vitro anti-HIV activity, and preliminary stability studies of several mononucleoside phosphorodithiolate derivatives incorporating a new kind of biolabile phosphate-protection, namely O-pivaloyl-2-oxyethyl, are reported. Our preliminary results strongly support the hypothesis that such pronucleotides exert their biological effects via intracellular delivery of the corresponding 5'-mononucleotide.

  DOI：

  10.1080/07328319708006180

文献信息

• Mononucleoside phosphorodithiolates as mononucleotide prodrugs
  作者：Nathalie Schlienger、Isabelle Lefebvre、Anne-Marie Aubertin、Suzanne Peyrottes、Christian Périgaud

  DOI：10.1016/j.ejmech.2021.113914

  日期：2022.1

  The synthesis and in vitro anti-HIV activity of a novel series of pronucleotides are reported. These prodrugs were characterized by a phosphorodithiolate structure, incorporating two O-pivaloyl-2-oxyethyl substituents as biolabile phosphate protections. The compounds were obtained following an original one-pot three-step procedure, involving the formation of a phosphorodithioite intermediate which

  报道了一系列新型原核苷酸的合成和体外抗 HIV 活性。这些前药的特征在于二硫代磷酸酯结构，结合了两个O -pivaloyl-2-oxyethyl 取代基作为生物不稳定的磷酸盐保护。这些化合物是按照原始的一锅三步程序获得的，包括形成原位氧化的二硫代磷酸酯中间体。在体外，比较抗 HIV 评估表明，这种原始前药能够使相应的 5'-单核苷酸在细胞内有效释放。2',3'-双脱氧腺苷 (ddA) 3的前核苷酸在各种细胞系中表现出非常有效的抗逆转录病毒作用，在纳摩尔浓度范围内具有 50% 的有效浓度 (EC 50 ) 值。在原代单核细胞/巨噬细胞中，该衍生物抑制 HIV 复制的效力 (EC 50 0.23 pM) 是 ddA 的500 倍，前药的选择性指数是母体核苷的 50 倍。
• The Pronucleotide Approach. I. Synthesis, Anti-HIV Activity and Preliminary Stability Studies of Mononucleoside<i>S,S</i>′-Bis(O-acyl-2-oxyethyl) Phosphorodithiolates
  作者：N. Schlienger、C. Périgaud、G. Gosselin、I. Lefebvre、A. Pompon、A.-M. Aubertin、A. Kirn、J.-L. Imbach

  DOI：10.1080/07328319708006180

  日期：1997.7

  The synthesis, in vitro anti-HIV activity, and preliminary stability studies of several mononucleoside phosphorodithiolate derivatives incorporating a new kind of biolabile phosphate-protection, namely O-pivaloyl-2-oxyethyl, are reported. Our preliminary results strongly support the hypothesis that such pronucleotides exert their biological effects via intracellular delivery of the corresponding 5'-mononucleotide.