8-[(3'-azido-2',3'-dideoxythymidinyl)-5'-yl]octandioate | 256390-95-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 8-[(3'-azido-2',3'-dideoxythymidinyl)-5'-yl]octandioate
• 英文别名: 8-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy]-8-oxo-octanoic acid；8-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]-8-oxooctanoic acid
• CAS: 256390-95-1
• 化学式: C₁₈H₂₅N₅O₇
• 分子量: 423.426
• InChiKey: JBUJDCAWBLPIMD-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  辛二酸 、 齐多夫定 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以20%的产率得到8-[(3'-azido-2',3'-dideoxythymidinyl)-5'-yl]octandioate
  参考文献：
  名称：

  Synthesis and biological evaluation of 5′-O-dicarboxylic fatty acyl monoester derivatives of anti-HIV nucleoside reverse transcriptase inhibitors

  摘要：

  A number of 5 '-O-dicarboxylic fatty acyl monoester derivatives of 3 '-azido-3 '-deoxythymidine (zidovudine, AZT), 2 ',3 '-didehydro-2 ',3 '-dideoxythymidine (stavudine, d4T), and 3 '-fluoro-3 '-deoxythymidine (alovudine, FLT) were synthesized to improve the lipophilicity and potentially the cellular delivery of parent polar 2 ',3 '-dideoxynucleoside (ddN) analogs. The compounds were evaluated for their anti-HIV activity. Three different fatty acids with varying chain length of suberic acid (octanedioic acid), sebacic acid (decanedioic acid), and dodecanedioic acid were used for the conjugation with the nucleosides. The compounds were evaluated for anti-HIV activity and cytotoxicity. All dicarboxylic ester conjugates of nucleosides exhibited significantly higher anti-HIV activity than that of the corresponding parent nucleoside analogs. Among all the tested conjugates, 5 '-O-suberate derivative of AZT (EC50 = 0.10 nM) was found to be the most potent compound and showed 80-fold higher anti-HIV activity than AZT without any significant toxicity (TC50>500 nM). (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2014.02.001

文献信息

• Synthesis and biological evaluation of 5′-O-dicarboxylic fatty acyl monoester derivatives of anti-HIV nucleoside reverse transcriptase inhibitors
  作者：Bhanu Pemmaraju、Hitesh K. Agarwal、Donghoon Oh、Karen W. Buckheit、Robert W. Buckheit、Rakesh Tiwari、Keykavous Parang

  DOI：10.1016/j.tetlet.2014.02.001

  日期：2014.3

  A number of 5 '-O-dicarboxylic fatty acyl monoester derivatives of 3 '-azido-3 '-deoxythymidine (zidovudine, AZT), 2 ',3 '-didehydro-2 ',3 '-dideoxythymidine (stavudine, d4T), and 3 '-fluoro-3 '-deoxythymidine (alovudine, FLT) were synthesized to improve the lipophilicity and potentially the cellular delivery of parent polar 2 ',3 '-dideoxynucleoside (ddN) analogs. The compounds were evaluated for their anti-HIV activity. Three different fatty acids with varying chain length of suberic acid (octanedioic acid), sebacic acid (decanedioic acid), and dodecanedioic acid were used for the conjugation with the nucleosides. The compounds were evaluated for anti-HIV activity and cytotoxicity. All dicarboxylic ester conjugates of nucleosides exhibited significantly higher anti-HIV activity than that of the corresponding parent nucleoside analogs. Among all the tested conjugates, 5 '-O-suberate derivative of AZT (EC50 = 0.10 nM) was found to be the most potent compound and showed 80-fold higher anti-HIV activity than AZT without any significant toxicity (TC50>500 nM). (c) 2014 Elsevier Ltd. All rights reserved.