N¹-cholesteryloxycarbonyl-4,9-diazadodecane-1,12-diamine

• 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: N¹-cholesteryloxycarbonyl-4,9-diazadodecane-1,12-diamine
• 英文别名: cholesterol spermine carbamate；N1-cholesteryloxy-carbonyl-4,9-diaza-1,12-dodecanediamine；[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] N-[3-[4-(3-aminopropylamino)butylamino]propyl]carbamate
• 化学式: C₃₈H₇₀N₄O₂
• 分子量: 614.999
• InChiKey: LLBWQHMRQZDPDP-HMVYLTCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  44
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  88.4
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  精胺 在 TEA 、 氨 、 水 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N¹-cholesteryloxycarbonyl-4,9-diazadodecane-1,12-diamine
  参考文献：
  名称：

  Synthesis of cholesterol-polyamine carbamates: pKa studies and condensation of calf thymus DNA

  摘要：

  我们制备了新型胆固醇-多胺氨基甲酸酯，并通过电位计测定了它们与最多五个氨基官能团取代的共轭物的 pKas，还测定了它们与小牛胸腺 DNA 的结合亲和力；这些多胺氨基甲酸酯是基因递送（脂质体感染）方面脂质体形成的模型，而脂质体感染是基因治疗的关键第一步。

  DOI：

  10.1039/a803284j

文献信息

• Novel compositions of TLR7 and/or TLR8 agonists conjugated to lipids
  申请人：Invivogen

  公开号：EP2674170B1

  公开（公告）日：2014-11-19
• Polyamine Analogues of 3β-[N-(N′,N′-Dimethylaminoethane)carbamoyl]cholesterol (DC-Chol) as Agents for Gene Delivery
  作者：Robert G. Cooper、Christopher J. Etheridge、Luisa Stewart、John Marshall、Samantha Rudginsky、Seng H. Cheng、Andrew D. Miller

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

  日期：1998.1

  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.
• The facile solid-phase synthesis of cholesterol-based polyamine lipids
  作者：Morag Oliver、Michael R. Jorgensen、Andrew Miller

  DOI：10.1016/j.tetlet.2004.02.093

  日期：2004.4

  A facile solid-phase methodology for the production of cholesterol-based polyamines useful in mediating nucleic acid delivery for gene therapy is described, The methodology is compatible with a range of polyamine, producing a library of lipid, in excellent yields (>87%) and purity. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis of cholesterol-polyamine carbamates: pKa studies and condensation of calf thymus DNA
  作者：Andrew J. Geall、Ian S. Blagbrough、Andrew J. Geall、Richard J. Taylor、Mark E. Earll、Michael A. W. Eaton

  DOI：10.1039/a803284j

  日期：——

  Novel cholesterol-polyamine carbamates have been prepared and their pKas determined potentiometrically for conjugates substituted with up to five amino functional groups and the binding affinity for calf thymus DNA has also been determined; these polyamine carbamates are models for lipoplex formation with respect to gene delivery (lipofection), a key first step in gene therapy.

  我们制备了新型胆固醇-多胺氨基甲酸酯，并通过电位计测定了它们与最多五个氨基官能团取代的共轭物的 pKas，还测定了它们与小牛胸腺 DNA 的结合亲和力；这些多胺氨基甲酸酯是基因递送（脂质体感染）方面脂质体形成的模型，而脂质体感染是基因治疗的关键第一步。