(cholest-5-en-3β-yl) imidazole-1-carboxylate | 773157-19-0

• 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: (cholest-5-en-3β-yl) imidazole-1-carboxylate
• 英文别名: Cholest-5-en-3beta-yl imidazole-1-carboxylate；[(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] imidazole-1-carboxylate
• CAS: 773157-19-0
• 化学式: C₃₁H₄₈N₂O₂
• 分子量: 480.734
• InChiKey: SMXILNGNXQGVQX-GTPODGLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (cholest-5-en-3β-yl) imidazole-1-carboxylate 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.5h， 生成 5'-O-(dimethoxytrityl)-4'-C-[N-(cholesteryloxycarbonyl)aminoethyl]thymidine
  参考文献：
  名称：

  Nucleosides and Nucleotides. Part 206: Introduction of Lipophilic Groups into 4′α-C-(2-Aminoethyl)thymidine-Containing Phosphodiester Oligodeoxynucleotides and Thermal Stabilities of the Duplexes

  摘要：

  Synthesis and properties of the 4'alpha-C-(2-aminoethyl)thymidine (1)-containing oligodeoxynucleotides (ODNs), which have lipophilic groups such as palmitic acid, oleic acid, and cholesterol at the terminal of the aminoethyl linker of the compound 1, are described. The ODNs were synthesized in a DNA synthesizer by using controlled pore glasses (CPGs) having the 4'alpha-C-[N-(palmitoyl), N-(oleoyl), and N-(cholesteryloxycarbonyl)aminoethyl]thymidine analogs (9a, b, and c). The stability of the duplexes formed by these ODNs and a complementary DNA 15 or RNA 16 was studied by thermal denaturation. It was found that the bulky functional group such as cholesterol thermally destabilizes the DNA/DNA duplexes, but that such thermal destabilization can be offset by the effects of the aminoethyl linker of 1. Furthermore, these lipophilic groups do not largely influence the thermal stability of the DNA/RNA duplexes. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00705-5
• 作为产物：
  描述：

  胆固醇 、 N,N'-羰基二咪唑 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (cholest-5-en-3β-yl) imidazole-1-carboxylate
  参考文献：
  名称：

  Synthesis of lipid mediators based on 1,2-dialkylglycerol and cholesterol for targeted delivery of oligo- and polynucleotides into hepatocytes

  摘要：

  所述内容为阳离子糖脂的合成，其中含有半乳糖或乳糖残基，作为肝细胞靶向标记。

  DOI：

  10.1007/s11172-010-0070-y

文献信息

• Synthesis of polycationic lipids based on cholesterol and spermine
  作者：I. A. Petukhov、M. A. Maslov、N. G. Morozova、G. A. Serebrennikova

  DOI：10.1007/s11172-010-0071-x

  日期：2010.1

  The synthesis of cholesterol-based cationic lipids in which the hydrophobic steroidal fragment is linked to a spermine residue as the hydrophilic domain by ester or carbamate linkage is described.

  文中描述了胆固醇基阳离子脂质的合成方法，其中疏水性的甾体片段通过酯或氨基甲酸酯键与亲水性的精胺残基相连接。
• Structure–transfection activity relationships in a series of novel cationic lipids with heterocyclic head-groups
  作者：Ekaterina A. Ivanova、Mikhail A. Maslov、Tatyana O. Kabilova、Pavel A. Puchkov、Anna S. Alekseeva、Ivan A. Boldyrev、Valentin V. Vlassov、Galina A. Serebrennikova、Nina G. Morozova、Marina A. Zenkova

  DOI：10.1039/c3ob40442k

  日期：——

  Cationic liposomes are promising candidates for the delivery of various therapeutic nucleic acids. Here, we report a convenient synthesis of carbamate-type cationic lipids with various hydrophobic domains (tetradecanol, dialkylglycerol, cholesterol) and positively charged head-groups (pyridinium, N-methylimidazolium, N-methylmorpholinium) and data on the structure–transfection activity relationships. It was found that single-chain lipids possess high surface activity, which correlates with high cytotoxicity due to their ability to disrupt the cellular membrane by combined hydrophobic and electrostatic interactions. Liposomes containing these lipids also display high cytotoxicity with respect to all cell lines. Irrespective of chemical structures, all cationic lipids form liposomes with similar sizes and surface potentials. The characteristics of complexes composed of cationic liposomes and nucleic acids depend mostly on the type of nucleic acid and P/N ratios. In the case of oligodeoxyribonucleotide delivery, the transfection activity depends on the type of cationic head-group regardless of the type of hydrophobic domain: all types of cationic liposomes mediate efficient oligonucleotide transfer into 80–90% of the eukaryotic cells, and liposomes based on lipids with N-methylmorpholinium cationic head-group display the highest transfection activity. In the case of plasmid DNA and siRNA, the type of hydrophobic domain determines the transfection activity: liposomes composed of cholesterol-based lipids were the most efficient in DNA transfer, while liposomes containing glycerol-based lipids exhibited reasonable activity in siRNA delivery under serum-free conditions.

  阳离子脂质体是输送各种治疗性核酸的有前景的候选物。这里，我们报告了一种方便的合成方法，合成含有各种疏水域（十四烷醇、二烷基甘油、胆固醇）和正电荷头部基团（吡啶鎓、N-甲基咪唑鎓、N-甲基吗啉鎓）的氨基甲酸酯型阳离子脂质，并提供了结构-转染活性关系的数据。研究发现，单链脂质具有高表面活性，这与其通过疏水和静电相互作用破坏细胞膜的能力相关，导致高细胞毒性。含有这些脂质的脂质体对所有细胞系也显示高细胞毒性。不管化学结构如何，所有阳离子脂质形成的脂质体具有相似的尺寸和表面电位。由阳离子脂质体和核酸组成的复合物的特性主要取决于核酸类型和P/N比率。在寡脱氧核苷酸输送的情况下，转染活性取决于阳离子头部基团的类型，无论疏水域的类型如何：所有类型的阳离子脂质体都能有效地将寡核苷酸转移到80-90%的真核细胞中，而基于含有N-甲基吗啉鎓阳离子头部基团的脂质的脂质体显示出最高的转染活性。在质粒DNA和siRNA的情况下，疏水域的类型决定了转染活性：由基于胆固醇的脂质组成的脂质体在DNA转移中最有效，而含有基于甘油的脂质的脂质体在无血清条件下在siRNA输送中显示出合理的活性。
• [EN] FUNCTIONALIZED LIPOSOMES USEFUL FOR THE DELIVERY OF BIOACTIVE COMPOUNDS<br/>[FR] LIPOSOMES FONCTIONNALISÉS UTILES POUR L'ADMINISTRATION DE COMPOSÉS BIOACTIFS
  申请人：CONSEJO SUPERIOR INVESTIGACION

  公开号：WO2014001509A1

  公开（公告）日：2014-01-03

  The invention relates to conjugates in which a sterol is functionalized by an ether bond with a water-soluble polymer to which a guiding ligand is bound. These conjugates improve the physico-chemical and delivery properties of their carrying vesicles, making these more stable, homogeneous and effective. A method for their preparation, a pharmaceutical composition containing said liposomes, and their therapeutic use are described as well.

  这项发明涉及共轭物，其中一种甾醇通过醚键与水溶性聚合物功能化，该聚合物上结合有引导配体。这些共轭物改善了它们携带的囊泡的物理化学和传递特性，使其更加稳定、均匀和有效。还描述了它们的制备方法、含有所述脂质体的药物组合物以及它们的治疗用途。
• PROCESS FOR PREPARING DC-CHOLESTEROL
  申请人：Palle Raghavendracharyulu Venkata

  公开号：US20070238889A1

  公开（公告）日：2007-10-11

  Processes for preparing 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (“DC-cholesterol”) and its salts.

  制备3β-[N-(N′,N′-二甲基氨基乙基)-氨甲酰基]胆固醇（“DC-胆固醇”）及其盐的过程。
• Spacer structure and hydrophobicity influences transfection activity of novel polycationic gemini amphiphiles
  作者：Pavel A. Puchkov、Irina A. Kartashova、Elena V. Shmendel、Anastasya S. Luneva、Nina G. Morozova、Marina A. Zenkova、Mikhail A. Maslov

  DOI：10.1016/j.bmcl.2017.06.026

  日期：2017.8

  properties and transfection efficiencies. Cationic liposomes formed by these amphiphiles and the helper lipid DOPE were able to successfully condense DNA, as shown by gel mobility shift and ethidium bromide intercalation assays. Transfection activity of the liposomes was superior to Lipofectamine® 2000 and was dependent on spacer structure, hydrophobicity, and nucleic acid type (pDNA or siRNA). We demonstrated

  开发了三种具有不同间隔基的新型双阳离子双阳离子双亲物，并对其理化性质和转染效率进行了评估。由这些两亲物和辅助脂质DOPE形成的阳离子脂质体能够成功地凝结DNA，如凝胶迁移率变化和溴化乙锭插层分析所示。脂质体的转染活性优于脂质体® 2000和依赖于间隔物结构，疏水性和核酸类型（质粒DNA或siRNA）。我们证明了阳离子脂质体2X6 / DOPE和2X7 / DOPE是潜在的无毒载体，可用于基因传递。