N¹,N⁴-bis-(benzyloxycarbonyl)-1-amino-4-azaoctanol-8 | 204061-18-7

• 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: N¹,N⁴-bis-(benzyloxycarbonyl)-1-amino-4-azaoctanol-8
• CAS: 204061-18-7
• 化学式: C₂₃H₃₀N₂O₅
• 分子量: 414.502
• InChiKey: YEILOJPITVMQNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  30.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  88.1
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N¹,N⁴-bis-(benzyloxycarbonyl)-1-amino-4-azaoctanol-8 在 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 苯 为溶剂， 反应 42.0h， 生成 N⁹,N¹²-bis-(benzyloxycarbonyl)-1,12-diamino-2,2-dimethyl-4,9-diazadodecane
  参考文献：
  名称：

  研究新型C-甲基化精胺衍生物揭示的多胺代谢调控的不可预见的可能性。

  摘要：

  生物多胺，精胺（Spm）和亚精胺是参与参与重要细胞功能（包括增殖和分化）调节的所有真核细胞中以毫摩尔浓度存在的有机聚阳离子。多胺类似物的设计和生化评估是多胺研究的基础。在这里，我们合成和研究了新颖的C-甲基化Spm类似物：2,11-二甲基精胺（2,11-Me2Spm），3,10-二甲基精胺（3,10-Me2Spm），2-甲基精胺和2,2-二甲基精胺。所测试的类似物克服了鸟氨酸脱羧酶（ODC）抑制剂α-二氟甲基鸟氨酸72 h诱导的生长停滞，并通过多胺转运蛋白进入DU145细胞。3，与2,11-Me2Spm相比，10-Me2Spm是精胺氧化酶和亚精胺/亚精胺-N1-乙酰基转移酶（SSAT）的较差底物，因此类似于1,12-二甲基精胺，它缺少SSAT反应所需的底物性质。由抗酶（OAZ1）介导的ODC下调和多胺转运的抑制对于维持多胺体内稳态至关重要。有趣的是，发现3,10-Me2Spm是第一个不会诱

  DOI：

  10.1021/acs.jmedchem.9b01666
• 作为产物：
  描述：

  {3-[4-(tert-Butyl-diphenyl-silanyloxy)-butylamino]-propyl}-carbamic acid benzyl ester 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N¹,N⁴-bis-(benzyloxycarbonyl)-1-amino-4-azaoctanol-8
  参考文献：
  名称：

  Polyamine Analogues of 3β-[N-(N′,N′-Dimethylaminoethane)carbamoyl]cholesterol (DC-Chol) as Agents for Gene Delivery

  摘要：

  Cationic liposomes are rapidly proving very effective at mediating the delivery of genes to cells in vitro. Moreover, the use of cationic liposomes for gene delivery in vivo is now under consideration. In previous work, we were able to demonstrate that cationic liposomes, formulated from 3 beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol) and the neutral phospholipid, dioleoyl L-alpha-phosphatidylethanolamine (DOPE), were able to transfect the lungs of mice in vivo. However, it rapidly became apparent that substantial improvements in the gene delivery efficiency, by approximately two orders of magnitude, would be needed for human lung transfection to be possible. In the following paper we describe the synthesis of a range of polyamine analogues of DC-Chol, which were formulated into cationic liposomes with DOPE and evaluated for efficiency of gene delivery in vitro and in vivo in mice. We report that cationic liposomes formulated from DOPE and the novel pentamine N-15-cholesteryloxycarbonyl-3,7,12-triazapentadecane-1,15-diamine (CTAP) were 100 times more efficient than DC-Chol/DOPE liposomes at gene delivery in vivo (500 times more effective than DNA alone). Therefore, we believe that CTAP/DOPE cationic liposomes should have clinical applications in human gene therapy approaches to the treatment of lung disorders as well as to other clinical conditions.

  DOI：

  10.1002/(sici)1521-3765(199801)4:1<137::aid-chem137>3.0.co;2-2