5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>carbonyl>benzoyl)-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid | 220481-75-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>carbonyl>benzoyl)-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid
• 英文别名: 5-[4,8-Bis[(2-methylpropan-2-yl)oxycarbonyl]-11-[4-[4,8,11-tris[(2-methylpropan-2-yl)oxycarbonyl]-1,4,8,11-tetrazacyclotetradecane-1-carbonyl]benzoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]pentanoic acid
• CAS: 220481-75-4
• 化学式: C₅₈H₉₈N₈O₁₄
• 分子量: 1131.46
• InChiKey: GWSGJFOJBARBBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  80
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  229
• 氢给体数：
  1
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>carbonyl>benzoyl)-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid 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-trihydrochloride-11-<4-<(4,8,11-trihydrochloride-1,4,8,11-tetraazacyclotetradecanyl)carbonyl>benzoyl>-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：

  对苯二甲酰氯 、 1,4,8-三(叔丁氧碳酰)-1,4,8,11-四氮杂环十四烷 、 5-<4,8-bis(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoic ethyl ester 在 sodium hydroxide 、 苄基三甲基氢氧化铵 、 碳酸氢钠 作用下， 生成 Tritert-butyl 11-[4-[4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetrazacyclotetradecane-1-carbonyl]benzoyl]-1,4,8,11-tetrazacyclotetradecane-1,4,8-tricarboxylate 、 5-<4,8-bis(tert-butyloxycarbonyl)-11-(4-<<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>carbonyl>benzoyl)-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid 、 1,1'-terephthaloyl-bis<4,8,11-bis(tert-butoxycarbonyl)-11-pentanoic acid-1,4,8,11-tetraazacyclotetradecane>
  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

• New Bicyclam−AZT Conjugates:  Design, Synthesis, Anti-HIV Evaluation, and Their Interaction with CXCR-4 Coreceptor
  作者：Jean Dessolin、Pascale Galea、Patrick Vlieghe、Jean-Claude Chermann、Jean-Louis Kraus

  DOI：10.1021/jm980358u

  日期：1999.1.1

  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.