5-<4,8-bis(tert-butyloxycarbonyl)-11-<5-oxo-5-<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid | 203568-35-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 5-<4,8-bis(tert-butyloxycarbonyl)-11-<5-oxo-5-<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid
• 英文别名: 5-[4,8-Bis[(2-methylpropan-2-yl)oxycarbonyl]-11-[5-oxo-5-[4,8,11-tris[(2-methylpropan-2-yl)oxycarbonyl]-1,4,8,11-tetrazacyclotetradec-1-yl]pentanoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]pentanoic acid
• CAS: 203568-35-8
• 化学式: C₅₅H₁₀₀N₈O₁₄
• 分子量: 1097.44
• InChiKey: PAQXBSMBNVIVEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  77
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 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-<5-oxo-5-<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 生成 5-[11-[5-Oxo-5-(1,4,8,11-tetrazacyclotetradec-1-yl)pentanoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]pentanoic acid
  参考文献：
  名称：

  Syntheses of new unsymmetrical bispolyazamacrocycles

  摘要：

  We report the synthesis of an original unsymmetrical bismacrocycle bearing a carboxylic side-arm. Two different synthetic pathways were investigated, both involving a Schotten-Baumann like reaction. The first route allowed us to obtain a mixture of compounds whilst the second one was direct and non-ambiguous. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(97)10748-1
• 作为产物：
  描述：

  戊二酰基二氯 、 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 1,1'-(1,5-dioxo-pentane)-bis<4,8-bis(tert-butyloxycarbonyl)-11-pentanoic acid-1,4,8,11-tetraazacyclotetradecane> 、 5-<4,8-bis(tert-butyloxycarbonyl)-11-<5-oxo-5-<4,8,11-tris(tert-butoxycarbonyl)-1,4,8,11-tetraazacyclotetradecanyl>pentanoyl>-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid 、 1,1'-(1,5-dioxo-pentane)-bis[4,8,11-tris(tert-butyloxycarbonyl)-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.
• Syntheses of new unsymmetrical bispolyazamacrocycles
  作者：J. Dessolin、G. Quéléver、M. Camplo、J.L. Kraus

  DOI：10.1016/s0040-4039(97)10748-1

  日期：1998.2

  We report the synthesis of an original unsymmetrical bismacrocycle bearing a carboxylic side-arm. Two different synthetic pathways were investigated, both involving a Schotten-Baumann like reaction. The first route allowed us to obtain a mixture of compounds whilst the second one was direct and non-ambiguous. (C) 1998 Elsevier Science Ltd. All rights reserved.