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 | 220481-70-9

• 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>methyl>benzyl>-1,4,8,11-tetraazacyclotetradecanyl> pentanoic acid
• 英文别名: 5-{4,8-bis[(tert-butoxy)carbonyl]-11-{[4-({4,8,11-tris[(tert-butoxy)carbonyl]-1,4,8,11-tetraazacyclotetradecanyl}methyl)phenyl]methyl}-1,4,8,11-tetraazacyclotetradecanyl}pentanoic acid；5-[4,8-Bis[(2-methylpropan-2-yl)oxycarbonyl]-11-[[4-[[4,8,11-tris[(2-methylpropan-2-yl)oxycarbonyl]-1,4,8,11-tetrazacyclotetradec-1-yl]methyl]phenyl]methyl]-1,4,8,11-tetrazacyclotetradec-1-yl]pentanoic acid
• CAS: 220481-70-9
• 化学式: C₅₈H₁₀₂N₈O₁₂
• 分子量: 1103.49
• InChiKey: OLIGLFKUONUNNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  78
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  195
• 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>methyl>benzyl>-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-(1,4,8,11-tetrahydrochloride-11-<4-<(1,4,8,11-tetrahydrochloride-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
• 作为产物：
  描述：

  1,4,8,11-四氮杂环十四烷 在 苄基三甲基氢氧化铵 、 potassium carbonate 、 sodium iodide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 8.0h， 生成 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
  参考文献：
  名称：

  一种抗艾滋病毒药物及其制备方法

  摘要：

  一种抗艾滋病毒药物及其制备方法，本发明公开了一种雷特格韦衍生物酯及其制备方法，该雷特格韦衍生物酯的化学名称是：N‑(2’‑(4’‑(4’‑氟苄基氨基甲酰基)‑1’‑甲基‑6’‑氧代‑1’,6’‑二氢嘧啶‑2’‑基)‑5’‑甲基‑1’,3’,4’‑恶二唑‑2’‑甲酰胺‑5’‑氧‑{5‑[1,4,8,11‑四氮杂环十四烷基]甲基}苯基)‑1,4,8,11‑四氮杂环十四烷基]}‑R‑羧酸酯。其显示了比雷特格韦明显较高的活性（EC50）和选择性指数（SI=EC50/CC50），并显著增加了溶解性。

  公开号：

  CN105237526B

文献信息

• New bicyclam–GalCer analogue conjugates: synthesis and in vitro anti-HIV activity
  作者：Jean-Michel Daoudi、Jacques Greiner、Anne-Marie Aubertin、Pierre Vierling

  DOI：10.1016/j.bmcl.2003.10.036

  日期：2004.1

  The synthesis of bipharmacophore anti-HIV compounds which, in a single molecule, combine two ligands, that is, the bicyclam AMD3100 and a GalCer analogue, that might inhibit several steps of the complex virus/cell cascade interactions has been performed. The 'double-drug' Gal-AMD3100 conjugates elicited inhibitory effects on T (or X4)-tropic HIV-1 replication in all CXCR4 expressing cell lines with

  已经完成了双药效团抗HIV化合物的合成，该化合物在一个分子中结合了两个配体，即bicyclAM AMD3100和GalCer类似物，它们可能会抑制复杂病毒/细胞级联相互作用的多个步骤。“双药” Gal-AMD3100偶联物在所有表达CXCR4的细胞系中EC（50）值从0.25到6.0 microM的T（或X4）嗜性HIV-1复制引起抑制作用，然而，其值约为0.25至6.0 microM。比AMD3100低125倍。关于Gal-AMD3100偶联物的抑制机制，用X4或R5HIV-1菌株和经过基因修饰以表达CD4和CXCR4或CCR5的GHOST细胞进行的实验清楚地表明，偶联物与CXCR4相互作用，而不与CCR5相互作用。