3'-azido-3'-deoxy-5'-O-<5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>methyl>benzyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>thymidine | 220481-72-1

• 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: 3'-azido-3'-deoxy-5'-O-<5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>methyl>benzyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>thymidine
• 英文别名: tritert-butyl 11-[[4-[[11-[5-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy]-5-oxo-pentyl]-4,8-bis(tert-butoxycarbonyl)-1,4,8,11-tetrazacyclotetradec-1-yl]methyl]phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane-1,4,8-tricarboxylate；tritert-butyl 11-[[4-[[11-[5-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]-5-oxopentyl]-4,8-bis[(2-methylpropan-2-yl)oxycarbonyl]-1,4,8,11-tetrazacyclotetradec-1-yl]methyl]phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane-1,4,8-tricarboxylate
• CAS: 220481-72-1
• 化学式: C₆₈H₁₁₃N₁₃O₁₅
• 分子量: 1352.72
• InChiKey: IBFUSWPRJRIJDE-SQTUBTBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  96
• 可旋转键数：
  24
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  257
• 氢给体数：
  1
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  3'-azido-3'-deoxy-5'-O-<5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>methyl>benzyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>thymidine 生成 3'-azido-3'-deoxy-5'-O-<5-(11-<4-<(1,4,8,11-tetraazacyclotetradecanyl)methyl>benzyl>-1,4,8,11-tetraazacyclotetradecanyl)pentanoyl>thymidine
  参考文献：
  名称：

  New Polyazamacrocycle-Nucleoside Conjugates: Synthesis, Anti-HIV Evaluation and Interaction with CXCR-4 Coreceptor

  摘要：

  We report the synthesis of new conjugates that incorporate in their structure bis-tetraazamacrocycle coupled with AZT via enzymolabile bond.Two series of bis-polyazamacrocycles-AZT conjugates were designed, synthesized and evaluated for their antiviral effect in vitro as well as their capability to bind to CXCR-4 coreceptor.

  DOI：

  10.1080/15257779908041591
• 作为产物：
  描述：

  齐多夫定 、 5-<4,8-bis(tert-butyloxycarbonyl)-11-<4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>methyl>benzyl>-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid 在 4-二甲氨基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以35%的产率得到3'-azido-3'-deoxy-5'-O-<5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>methyl>benzyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>thymidine
  参考文献：
  名称：

  New Bicyclam−AZT Conjugates:  Design, Synthesis, Anti-HIV Evaluation, and Their Interaction with CXCR-4 Coreceptor

  摘要：

  We report the synthesis of mono- and bis-tetraazamacrocycle-AZT conjugates. All new compounds were screened for their ability to inhibit HIV-1 replication in MT4 cell line and were compared to AZT alone. It appears that N-protected covalent prodrugs are equipotent to AZT as inhibitor of HIV replication, while N-deprotected analogues exhibit both higher activity and selectivity against HIV-infected cells. The most active antiviral compounds 27, 28, 34, and 35 were then tested for their binding capability to CXCR-4 receptor. N-Boc analogues 27 and 34 were only weakly effective; in contrast, N-deprotected conjugates 28 and 35 were antagonists to 12G5 mAb binding until 0.05 and 5 mu g/mL, respectively. The stability of compound 28 in human plasma was evaluated, and half-life was found to be approximately 8 h in the described conditions. All these results seem to demonstrate the confidence of our prodrug approach, with analogue 28 emerging as the best candidate as lead compound in HIV-1 polytherapy perspective.

  DOI：

  10.1021/jm980358u