[(S)-5-Amino-5-(2-dihexadecylamino-ethylcarbamoyl)-pentyl]-carbamic acid tert-butyl ester | 876066-00-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(S)-5-Amino-5-(2-dihexadecylamino-ethylcarbamoyl)-pentyl]-carbamic acid tert-butyl ester
• CAS: 876066-00-1
• 化学式: C₄₅H₉₂N₄O₃
• 分子量: 737.25
• InChiKey: CENQRMCVMQZWJG-WBCKFURZSA-N

物化性质

• 沸点：
  793.8±60.0 °C(Predicted)
• 密度：
  0.920±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  12.39
• 重原子数：
  52.0
• 可旋转键数：
  39.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  96.69
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [(S)-5-Amino-5-(2-dihexadecylamino-ethylcarbamoyl)-pentyl]-carbamic acid tert-butyl ester 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 N-(2-((S)-6-((tert-butoxycarbonyl)amino)-2-((3R,4S,5R)-3,4,5-triacetoxycyclohex-1-ene-1-carboxamido)hexanamido)ethyl)-N-hexadecyl-N-methylhexadecan-1-aminium iodide
  参考文献：
  名称：

  [EN] NOVEL CATIONIC AMPHIPHILES WITH MANNOSE-MIMICKING HEAD-GROUPS AND A PROCESS FOR THE PREPARATION THEREOF
  [FR] NOUVEAUX AMPHIPHILES CATIONIQUES À TÊTES POLAIRES IMITANT LA MANNOSE, ET LEURS MÉTHODES DE PRÉPARATION

  摘要：

  本发明公开了包含类似于甘露糖的樟脑酸和奎尼酸头基的新型阳离子两性分子，以及一种制备具有类似于甘露糖极性头基的阳离子两性分子（如樟脑酸和奎尼酸）的方法。本文描述的研究结果还表明，本发明的化合物可以通过APC（抗原呈递细胞）如巨噬细胞和树突状细胞表面上表达的甘露糖受体，将模型DNA疫苗定位到目标细胞。与其甘露基对照相比，本文披露的阳离子两性分子在小鼠基因免疫中表现出更强的细胞和体液免疫应答。本发明中描述的具有类似于甘露糖的奎尼酸和樟脑酸头基的阳离子两性分子可能在基因免疫领域找到未来的应用。

  公开号：

  WO2012035557A1
• 作为产物：
  描述：

  N-2-aminoethyl-N,N-di-n-hexadecylamine 在 10 wt% Pd(OH)2 on carbon 盐酸 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、202.66 kPa 条件下， 反应 26.5h， 生成 [(S)-5-Amino-5-(2-dihexadecylamino-ethylcarbamoyl)-pentyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] NOVEL CATIONIC AMPHIPHILES WITH MANNOSE-MIMICKING HEAD-GROUPS AND A PROCESS FOR THE PREPARATION THEREOF
  [FR] NOUVEAUX AMPHIPHILES CATIONIQUES À TÊTES POLAIRES IMITANT LA MANNOSE, ET LEURS MÉTHODES DE PRÉPARATION

  摘要：

  本发明公开了包含类似于甘露糖的樟脑酸和奎尼酸头基的新型阳离子两性分子，以及一种制备具有类似于甘露糖极性头基的阳离子两性分子（如樟脑酸和奎尼酸）的方法。本文描述的研究结果还表明，本发明的化合物可以通过APC（抗原呈递细胞）如巨噬细胞和树突状细胞表面上表达的甘露糖受体，将模型DNA疫苗定位到目标细胞。与其甘露基对照相比，本文披露的阳离子两性分子在小鼠基因免疫中表现出更强的细胞和体液免疫应答。本发明中描述的具有类似于甘露糖的奎尼酸和樟脑酸头基的阳离子两性分子可能在基因免疫领域找到未来的应用。

  公开号：

  WO2012035557A1

文献信息

• [EN] MANNOSE-RECEPTOR SELECTIVE LYSINYLATED CATIONIC AMPHIPHILES AND A PROCESS FOR PREPARATION THEREOF<br/>[FR] AMPHIPHILES CATIONIQUES LYSINYLÉS SÉLECTIFS DU RÉCEPTEUR AU MANNOSE ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2014106856A1

  公开（公告）日：2014-07-10

  The present invention relates to the mannose - receptor selective lysinylated cationic amphiphile and a process for preparation thereof. The compounds of the present invention can target DNA vaccines to antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs), via mannose receptors expressed on the cell surface of APCs. The cationic amphiphiles disclosed herein show enhanced cellular and humoral immune response compared to their mannosyl counterparts in genetic immunization in mice. The present invention discloses that immunization with electrostatic complexes (lipoplexes) of DNA vaccines encoding melanoma antigens (gp100 and tyrosinase) and liposome of the presently described novel lysinylated cationic amphiphiles with mannose-mimicking shikimoyl head-groups provides long-lasting (100 days post melanoma tumor challenge) protective immunity in all immunized mice. Cationic amphiphiles with mannose-mimicking shikimoyl head-groups described in the present invention are likely to find future applications in the field of genetic immunization.

  本发明涉及甘露糖受体选择性赖氨酸化阳离子两性分子及其制备方法。本发明的化合物可以通过存在于抗原呈递细胞（APCs）如巨噬细胞和树突细胞（DCs）表面的甘露糖受体，将DNA疫苗靶向到这些细胞。本文披露的阳离子两性分子与其甘露基对照物相比，在小鼠基因免疫中显示出增强的细胞和体液免疫应答。本发明揭示，使用编码黑色素瘤抗原（gp100和酪氨酸酶）的DNA疫苗的静电复合物（脂质复合物）和目前描述的具有模拟甘露基的梭梗素头基的新型赖氨酸化阳离子两性分子的脂质体免疫，可以在所有免疫小鼠中提供持久的（挑战黑色素瘤肿瘤后100天）保护免疫。本发明中描述的具有模拟甘露基的梭梗素头基的阳离子两性分子可能在基因免疫领域找到未来的应用。
• Design, Syntheses and In Vitro Gene Delivery Efficacies of Novel Mono-, Di- and Trilysinated Cationic Lipids:  A Structure−Activity Investigation
  作者：Priya P. Karmali、Valluripalli V. Kumar、Arabinda Chaudhuri

  DOI：10.1021/jm030541+

  日期：2004.4.1

  Structure-activity investigation including design, syntheses, and evaluation of relative in vitro gene delivery efficacies of a novel series of cationic amphiphiles (1-10) containing mono-, di-, and trilysine headgroups are described in CHO, COS-1, and HepG2 cells. Several interesting and rather unexpected transfection profiles were observed. In general, lipid 1 with the myristyl tail used in combination with DOPE as colipid exhibited superior transfection properties compared to (a) the monolysinated analogues with longer hydrocarbon tails (lipids 2-4), (b) the dilysine (lipids 5-7) and the trilysine headgroup analogues (lipids 8-10), and (c) commercially available LipofectAmine with multiple positive charges in its polar region. As a preliminary estimate of the relative DNA-compacting efficacies of these new lysinated cationic lipids, the hydrodynamic diameters of representative lipoplexes were measured using dynamic laser light scattering technique. Our lipoplex size data are consistent with the notion that covalent grafting of an increasing number of positively charged functional groups in the headgroup region of cationic lipids need not necessarily result in more compacted lipoplexes. Both gel retardation and DNase I sensitivity assays indicated similar lipid/DNA binding interactions for all the novel mono-, di-, and trilysinated cationic lipids. MTT-assay-based cell viability results clearly demonstrate that the overall lower transfection properties of trilysine analogues (8-10) compared to their mono- (1-4) and dilysinated (5-7) counterparts are unlikely to originate from differential toxicity related effects. Taken together, the present findings support the notion that caution needs to be exercised in ensuring enhanced gene delivery efficacies of cationic lipids through covalent grafting of multiple lysine functionalities in the headgroup region.