bis(3'-azido-3'-deoxy-5'-thymidinyl) phosphate | 121135-54-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: bis(3'-azido-3'-deoxy-5'-thymidinyl) phosphate
• 英文别名: bis(3'-azido-3'-deoxythymidin-5-yl) phosphate；di(3'-azido-3'-deoxy-5'-thymidinyl) phosphate；AZTpAZT；bis[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl] hydrogen phosphate
• CAS: 121135-54-4
• 化学式: C₂₀H₂₅N₁₀O₁₀P
• 分子量: 596.453
• InChiKey: QNODVFYIEJIAOJ-KPRKPIBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  202
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  bis(3'-azido-3'-deoxy-5'-thymidinyl) phosphate 在 三乙胺 作用下， 以 四氯化碳 、 氯仿 为溶剂， 生成
  参考文献：
  名称：

  Design, synthesis, and antitumor activity of bile acid–polyamine–nucleoside conjugates

  摘要：

  A series of bile acid-polyamine amides conjugated with 3 '-azido-3 '-deoxythymidine (AZT) as potential antitumor prodrugs in the form of phosphoramidates were synthesized in good yields and their antitumor activities were assayed against two human cancer cells in vitro: cervix cancer HeLa cells and renal cancer 7860 cells. The improved antitumor activity probably derived from the enhanced delivery efficiency of AZT due to bile acid-polyamine conjugates. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.067
• 作为产物：
  描述：

  齐多夫定 在 四氮唑 、 2-(N,N-diisopropylamino)-2-oxo-1,3,2-oxathiaphospholane 、 叔丁基过氧化氢 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二甲基亚砜 、 癸烷 为溶剂， 反应 40.0h， 以65%的产率得到bis(3'-azido-3'-deoxy-5'-thymidinyl) phosphate
  参考文献：
  名称：

  Solid-Phase Synthesis of Dinucleoside and Nucleoside-Carbohydrate Phosphodiesters and Thiophosphodiesters

  摘要：

  Unprotected nucleosides (ROH) were reacted with two polymers bound to N, N-diisopropylamino- 1,3,2-oxathiaphospholane in the presence of 1H-terazole. Oxidation with tertbutyl hydroperoxide or sulfurization with Beaucage's reagent, followed by the 1,3,2-oxathiaphospholane ring opening with unprotected nucleosides or carbohydrates (R'OH) in the presence of DBU, afforded nucleoside-(5'-5')-nucleoside or nucleoside- carbohydrate phosphodiester and thiophosphodiester derivatives through the elimination of polymer-bound ethylene episulfide. This strategy offers the advantages of facile isolation of final products and monosubstitution of unprotected nucleosides and carbohydrates.

  DOI：

  10.1021/jo0611115

文献信息

• Synthesis, Bioactivation and Anti-HIV Activity of 4-Acyloxybenzyl<i>bis</i>(Nucleosid-5′-yl) Phosphates
  作者：Anne Routledge、Ian Walker、Sally Freeman、Alan Hay、Naheed Mahmood

  DOI：10.1080/15257779508009491

  日期：1995.9

  4-Acyloxybenzyl bis(nucleosid-5'-yl) phosphates 7a-c and 9a-c were prepared as potential prodrugs of the anti-HIV nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI) or their 5'-monophosphates.The anti-HIV activities of these triesters were determined in two T-cell lines. In a C8165 cell line they displayed activities comparable to and in some cases superior to AZT, but they also exhibited an increase in cytotoxicity. In a thymidine kinase deficient JM T-cell line the activity was reduced but was still superior to AZT. In the presence of porcine liver carboxyesterase (PLCE), triester 7b biodegrades to the diester 10 which, with phosphodiesterase, gives initially AZT monophosphate 3 and AZT.
• Meier, Chris; Habel, Lothar W.; Balzarini, Jan, Liebigs Annalen, 1995, # 12, p. 2203 - 2208
  作者：Meier, Chris、Habel, Lothar W.、Balzarini, Jan、Clercq, Eric De

  DOI：——

  日期：——
• Solid-Phase Synthesis of Dinucleoside and Nucleoside-Carbohydrate Phosphodiesters and Thiophosphodiesters
  作者：Yousef Ahmadibeni、Keykavous Parang

  DOI：10.1021/jo0611115

  日期：2006.8.1

  Unprotected nucleosides (ROH) were reacted with two polymers bound to N, N-diisopropylamino- 1,3,2-oxathiaphospholane in the presence of 1H-terazole. Oxidation with tertbutyl hydroperoxide or sulfurization with Beaucage's reagent, followed by the 1,3,2-oxathiaphospholane ring opening with unprotected nucleosides or carbohydrates (R'OH) in the presence of DBU, afforded nucleoside-(5'-5')-nucleoside or nucleoside- carbohydrate phosphodiester and thiophosphodiester derivatives through the elimination of polymer-bound ethylene episulfide. This strategy offers the advantages of facile isolation of final products and monosubstitution of unprotected nucleosides and carbohydrates.
• Design, synthesis, and antitumor activity of bile acid–polyamine–nucleoside conjugates
  作者：Dimao Wu、Sanhao Ji、Yan Wu、Yong Ju、Yufen Zhao

  DOI：10.1016/j.bmcl.2007.03.067

  日期：2007.6

  A series of bile acid-polyamine amides conjugated with 3 '-azido-3 '-deoxythymidine (AZT) as potential antitumor prodrugs in the form of phosphoramidates were synthesized in good yields and their antitumor activities were assayed against two human cancer cells in vitro: cervix cancer HeLa cells and renal cancer 7860 cells. The improved antitumor activity probably derived from the enhanced delivery efficiency of AZT due to bile acid-polyamine conjugates. (C) 2007 Elsevier Ltd. All rights reserved.