cholesteryl-(3-bromopropyl)carbamate | 204061-31-4

• 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: cholesteryl-(3-bromopropyl)carbamate
• 英文别名: [(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-bromopropyl)carbamate
• CAS: 204061-31-4
• 化学式: C₃₁H₅₂BrNO₂
• 分子量: 550.663
• InChiKey: SGBOPKGUTKDQLO-GTPODGLVSA-N

物化性质

• 沸点：
  594.248±39.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.142±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  cholesteryl-(3-bromopropyl)carbamate 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 草酰氯 、 四丁基氟化铵 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 、 三甲基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 19.5h， 生成 N1-cholesteryloxycarbonyl-4,9,14-triaza-N4,14,17-tri(phenylmethoxycarbonyl)heptadecane-1,17-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：

  cholesterol-3-(carboxyaminopropan-3-ol) 在 三乙胺 、 sodium bromide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 cholesteryl-(3-bromopropyl)carbamate
  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

• Lipids and compositions for the delivery of therapeutics
  申请人：Manoharan Muthiah

  公开号：US09186325B2

  公开（公告）日：2015-11-17

  The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alky lhetro cycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

  本发明提供了有利用于体内向细胞传递治疗剂的脂质颗粒中的脂质。具体而言，该发明的公式（I）提供了具有以下结构XXXIII的脂质，其中：R1和R2分别独立地为每次出现的情况下，可以是选择性取代的C10-C30烷基，选择性取代的C10-C30烯基，选择性取代的C10-C30炔基，选择性取代的C10-C30酰基，或-连接-配体；R3为H，可以是选择性取代的C1-C10烷基，选择性取代的C2-C10烯基，选择性取代的C2-C10炔基，烷基杂环，烷基磷酸酯，烷基磷硫酸酯，烷基磷二硫酸酯，烷基磷酸酯，烷基胺，羟基烷基，ω-氨基烷基，ω-(取代)氨基烷基，ω-磷酰基烷基，ω-硫代磷酰基烷基，选择性取代的聚乙二醇（PEG，分子量100-40K），选择性取代的mPEG（分子量120-40K），杂环芳基，杂环，或连接-配体；E为C(O)O或OC(O)。
• NUCLEIC ACID COMPLEXES
  申请人：Purdue Research Foundation

  公开号：US20150202323A1

  公开（公告）日：2015-07-23

  The invention relates to nucleic acid complexes, methods of preparation thereof, and uses thereof for delivering a nucleic acid into a cell.

  这项发明涉及核酸复合物，其制备方法以及将其用于将核酸输送到细胞中的用途。
• Pendant Polymer:Amino-β-Cyclodextrin:siRNA Guest:Host Nanoparticles as Efficient Vectors for Gene Silencing
  作者：Aditya Kulkarni、Kyle DeFrees、Seok-Hee Hyun、David H. Thompson

  DOI：10.1021/ja300690j

  日期：2012.5.9

  CHO-GFP cells shows that these materials have 10(3)-fold lower cytotoxicities than 25 kD bPEI, while maintaining gene-silencing efficiencies that are comparable to those of benchmark transfection reagents such as bPEI and Lipofectamine 2000. These results suggest that the degradable Chol-PVA-PEG polymer is able to self-assemble in the presence of siRNA and cationic-β-CD to form nanoparticles that are an

  基于单取代阳离子 β-CD 衍生物与聚（乙烯醇）MW27kD（PVA）主链聚合物（带有聚（乙二醇）MW2000（PEG）和酸-不稳定的胆固醇改性（Chol）通过酸敏感的亚苄基缩醛键接枝。使用两种不同的组装方案研究了这些成分与 siRNA 形成纳米颗粒的能力，包括在 siRNA 缩合之前预复合 Chol-PVA-PEG 聚合物与阳离子 β-CD 衍生物或 siRNA 与阳离子 β-CD 衍生物的缩合在添加 Chol-PVA-PEG 以进行宿主：客体复合之前。悬垂聚合物：氨基-β-CD：siRNA 复合物显示出形成尺寸范围为 120-170 nm 的纳米颗粒，具有略微负的 zeta 电位。
• Nucleic acid complexes
  申请人：Purdue Research Foundation

  公开号：US08916697B2

  公开（公告）日：2014-12-23

  The invention relates to nucleic acid complexes, methods of preparation thereof, and uses thereof for delivering a nucleic acid into a cell.

  这项发明涉及核酸复合物、其制备方法以及将其用于将核酸输送到细胞中的用途。
• POLYCATIONIC STEROL DERIVATIVES AS TRANSFECTION AGENTS
  申请人：IC-VEC LIMITED

  公开号：EP0918790B1

  公开（公告）日：2004-01-28