11-(4-Carboxy-butyl)-1,4,8,11-tetraaza-cyclotetradecane-1,4,8-tricarboxylic acid tri-tert-butyl ester | 203568-78-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂卓
• 英文名称: 11-(4-Carboxy-butyl)-1,4,8,11-tetraaza-cyclotetradecane-1,4,8-tricarboxylic acid tri-tert-butyl ester
• CAS: 203568-78-9
• 化学式: C₃₀H₅₆N₄O₈
• 分子量: 600.797
• InChiKey: NHJVQDJNGKQYLD-UHFFFAOYSA-N

物化性质

• 沸点：
  672.9±55.0 °C(Predicted)
• 密度：
  1.080±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.05
• 重原子数：
  42.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  129.16
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  11-(4-Carboxy-butyl)-1,4,8,11-tetraaza-cyclotetradecane-1,4,8-tricarboxylic acid tri-tert-butyl ester 在 盐酸 、 4-二甲氨基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3'-azido-3'-deoxy-5'-O-<5-<1,4,8,11-tetrahydrochloride-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
• 作为产物：
  描述：

  11-(4-Ethoxycarbonyl-butyl)-1,4,8,11-tetraaza-cyclotetradecane-1,4,8-tricarboxylic acid tri-tert-butyl ester 在 sodium hydroxide 、 苄基三甲基氢氧化铵 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以100%的产率得到11-(4-Carboxy-butyl)-1,4,8,11-tetraaza-cyclotetradecane-1,4,8-tricarboxylic acid tri-tert-butyl ester
  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

文献信息

• Tri-N-Boc-Tetraazamacrocycle-Nucleoside Conjugates: Synthesis and anti-HIV activities
  作者：J. Dessolin、P. Vlieghe、M. Bouygues、M. Medou、G. Qúéléver、M. Camplo、J. C. Chermann、J. L. Kraus

  DOI：10.1080/07328319808003466

  日期：1998.5

  As far as linear N-Boc-polyamines conjugates elicited remarkable anti-HIV activity, the synthesis and anti-HIV properties of cyclic N-Boc-polyamines conjugates such as tetraazamacro-cycle-nucleoside were studied. These new conjugates include an ester linkage between the two moieties. They were synthesized using Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate coupling reagent, in the case of N-alkyl polyazamacrocycle derivatives, or through direct condensation of the acyl chloride derivative with nucleoside in the case of N-acyl polyazamacrocycle compounds, None of the new conjugates presented anti-HIV activity greater than that of the corresponding parent nucleosides.