O-L-tyrosinyl O-(S-pivaloyl-2-thioethyl) 3'-azido-2',3'-deoxythymidin-5'-yl phosphate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: O-L-tyrosinyl O-(S-pivaloyl-2-thioethyl) 3'-azido-2',3'-deoxythymidin-5'-yl phosphate
• 英文别名: (2S)-2-amino-3-[4-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-[2-(2,2-dimethylpropanoylsulfanyl)ethoxy]phosphoryl]oxyphenyl]propanoic acid
• 化学式: C₂₆H₃₅N₆O₁₀PS
• 分子量: 654.638
• InChiKey: QOGKSQCJGWAVMF-UYMFWQTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  223
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  齐多夫定 在 四氮唑 、 盐酸 、 叔丁基过氧化氢 、 3 A molecular sieve 作用下， 以 乙醚 、 甲苯 、 乙腈 为溶剂， 反应 2.5h， 生成 O-L-tyrosinyl O-(S-pivaloyl-2-thioethyl) 3'-azido-2',3'-deoxythymidin-5'-yl phosphate
  参考文献：
  名称：

  S-Acyl-2-thioethyl Aryl Phosphotriester Derivatives as Mononucleotide Prodrugs

  摘要：

  The synthesis and biological activities of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a phenyl group or L-tyrosinyl residues are reported. The target compounds were obtained via either P-V or p(III) chemistry from the appropriate aryl precursors. All the derivatives were evaluated for their in vitro anti-HIV activity, and they appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments, with EC50 values between the micro- and nanomolar range. Furthermore, compounds incorporating an amino-and/or acid-substituted tyrosinyl residue demonstrated significant anti-HIV effects in thymidine kinase-deficient (TK-) cells showing their ability to act as mononucleotide prodrugs. The proposed decomposition process of these mixed mononucleoside aryl phosphotriesters may involve esterase activation followed by phosphodiesterase hydrolysis.

  DOI：

  10.1021/jm000996o

文献信息

• Rational design of a new series of mixed anti-HIV pronucleotides
  作者：Nathalie Schlienger、Thierry Beltran、Christian Périgaud、Isabelle Lefebvre、Alain Pompon、Anne-Marie Aubertin、Gilles Gosselin、Jean-Louis Imbach

  DOI：10.1016/s0960-894x(98)00535-6

  日期：1998.11

  MonoSATE aryl phosphotriesters of AZT are able to deliver intracellularly the corresponding 5'-mononucleotide. This process requires activation by an esterase followed by a phosphodiesterase. This finding opens the way to the design of hew pronucleotide series, (C) 1998 Elsevier Science Ltd. All rights reserved.
• <i>S</i>-Acyl-2-thioethyl Aryl Phosphotriester Derivatives as Mononucleotide Prodrugs
  作者：Nathalie Schlienger、Suzanne Peyrottes、Tarek Kassem、Jean-Louis Imbach、Gilles Gosselin、Anne-Marie Aubertin、Christian Périgaud

  DOI：10.1021/jm000996o

  日期：2000.11.1

  The synthesis and biological activities of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a phenyl group or L-tyrosinyl residues are reported. The target compounds were obtained via either P-V or p(III) chemistry from the appropriate aryl precursors. All the derivatives were evaluated for their in vitro anti-HIV activity, and they appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments, with EC50 values between the micro- and nanomolar range. Furthermore, compounds incorporating an amino-and/or acid-substituted tyrosinyl residue demonstrated significant anti-HIV effects in thymidine kinase-deficient (TK-) cells showing their ability to act as mononucleotide prodrugs. The proposed decomposition process of these mixed mononucleoside aryl phosphotriesters may involve esterase activation followed by phosphodiesterase hydrolysis.