3'-azido-3'-deoxythymidine-5'-O-β-triphosphate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3'-azido-3'-deoxythymidine-5'-O-β-triphosphate
• 英文别名: [[3-[(Imino-$l^{5}-azanylidene)amino]-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy-methylene-phosphonooxy-$l^{5}-phosphanyl] dihydrogen phosphate；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl diphosphono phosphate
• 化学式: C₁₀H₁₆N₅O₁₃P₃
• 分子量: 507.184
• InChiKey: RVVKNEWZZVFUFN-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.2
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  233
• 氢给体数：
  5
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  齐多夫定 生成 3'-azido-3'-deoxythymidine-5'-O-β-triphosphate
  参考文献：
  名称：

  Application of a Solid-Phase β-Triphosphitylating Reagent in the Synthesis of Nucleoside β-Triphosphates

  摘要：

  A beta-triphosphitylating reagent was subjected to reaction with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound beta-triphosphitylating reagent. The solid-phase reagent was reacted with unprotected nucleosides (e.g., 3'-azido-3'-deoxythymidine, cytidine, thymidine, uridine, inosine, or adenosine) in the presence of 1H-tetrazole. Polymer-bound nucleosides underwent oxidation with t-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford only monosubstituted 5'-O-beta-triphosphorylated nucleosides.

  DOI：

  10.1021/jo0610107

文献信息

• Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates
  作者：Chandravanu Dash、Yousef Ahmadibeni、Michael J. Hanley、Jui Pandhare、Mathias Gotte、Stuart F.J. Le Grice、Keykavous Parang

  DOI：10.1016/j.bmcl.2011.05.005

  日期：2011.6

  Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside beta-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3'-azido-2',3'-dideoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine (FLT), and 2',3'-didehydro-2',3'-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine beta-triphosphate (1) and AZT beta-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and nonnucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10 nM, 10 and 100 mu M, respectively. (C) 2011 Elsevier Ltd. All rights reserved.