N¹⁵-cholesteryloxycarbonyl-3,7,12-triaza-N^1,3,12-tri(phenylmethoxycarbonyl)pentadecane-1,15-diamine | 204061-35-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: N¹⁵-cholesteryloxycarbonyl-3,7,12-triaza-N^1,3,12-tri(phenylmethoxycarbonyl)pentadecane-1,15-diamine
• CAS: 204061-35-8
• 化学式: C₆₄H₉₃N₅O₈
• 分子量: 1060.47
• InChiKey: LJCWVEIEDFMUQV-SRMXJEAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.48
• 重原子数：
  77.0
• 可旋转键数：
  28.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  147.77
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N¹⁵-cholesteryloxycarbonyl-3,7,12-triaza-N^1,3,12-tri(phenylmethoxycarbonyl)pentadecane-1,15-diamine 在 palladium on activated charcoal 环己烯 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以99%的产率得到N¹⁵-cholesteryloxycarbonyl-3,7,12-triazapentadecane-1,15-diamine
  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
• 作为产物：
  描述：

  (2-Benzyloxycarbonylamino-ethyl)-[3-(tert-butyl-diphenyl-silanyloxy)-propyl]-carbamic acid benzyl ester 在 sodium tetrahydroborate 、 sodium azide 、 四丁基氟化铵 、 三乙胺 、 sodium iodide 、 三甲基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 N¹⁵-cholesteryloxycarbonyl-3,7,12-triaza-N^1,3,12-tri(phenylmethoxycarbonyl)pentadecane-1,15-diamine
  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

文献信息

• POLYCATIONIC STEROL DERIVATIVES AS TRANSFECTION AGENTS
  申请人：IC-VEC LIMITED

  公开号：EP0918790B1

  公开（公告）日：2004-01-28