8-(5-cholesten-3α-yloxy)-3n³₆-dioxaoctan-1-ol | 960624-08-2

• 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: 8-(5-cholesten-3α-yloxy)-3n³₆-dioxaoctan-1-ol
• 英文别名: 5-(cholesten-3-α-yloxy)-3,6-dioxaoctaol；2-[2-[2-[[(3R,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]oxy]ethoxy]ethoxy]ethanol
• CAS: 960624-08-2
• 化学式: C₃₃H₅₈O₄
• 分子量: 518.821
• InChiKey: VVUFLQVAKXEWGR-WUQYGKSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(5-cholesten-3α-yloxy)-3n³₆-dioxaoctan-1-ol 在 四丁基硫酸氢铵 、 对甲苯磺酸 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 24.0h， 生成 2-(2-(2-(2-(((3R,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)ethoxy)ethoxy)ethoxy)acetic acid
  参考文献：
  名称：

  一种双重脑肿瘤靶向脂质材料及其应用

  摘要：

  本发明公开了一种新型脂质材料，用于延长循环时间以及增加药物靶向传递至脑肿瘤组织。所述的新型脂质材料以聚乙二醇为桥连，一侧连接胆固醇，一侧连接葡萄糖和RGD肽，弥补单一葡萄糖或RGD肽修饰的脂质体脑肿瘤靶向能力的不足，实现跨血‑脑屏障后能够有效的靶向脑肿瘤。该新型脂质材料可用于脂质体、纳米粒、胶束等在内的不同剂型，所制成的载紫杉醇脂质体具有明显的脑肿瘤靶向功能，拥有广阔的应用前景。

  公开号：

  CN108743953B
• 作为产物：
  描述：

  胆甾-5-烯-3-醇 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 生成 8-(5-cholesten-3α-yloxy)-3n³₆-dioxaoctan-1-ol
  参考文献：
  名称：

  Design, synthesis and evaluation of liposomes modified with dendritic aspartic acid for bone-specific targeting

  摘要：

  Bone diseases are notoriously difficult diseases to treat due to the comparatively low blood flows in bone tissue. Therefore, targeting delivery of drugs to bone may not only enhance the treatment efficacy, but also reduce the quantity of drug administered. In order to increase the distribution of paclitaxel (PTX) in bone, in this study, a series of novel dendritic aspartic acid derivatives were designed and synthesized as liposome ligands to deliver PTX to bone effectively. The liposomes were prepared by thin film hydration method and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis were also characterized. All the aspartic acid-coated liposomes showed more than 60% binding rates to hydroxyapatite (HAP), especially the PTX-Asp(8)-Lip exhibited dramatic binding rates (> 97%) after 24 h. Moreover, the bone-targeting study in vivo indicated that all liposomes could improve the accumulation of PTX in bone, among which, the PTX-Asp(8)-Lip showed the best affinity due to the increase of aspartic acid residues exposed on the liposome surface. These results provided a novel and effective entry to the development of bone-targeting drugs.

  DOI：

  10.1016/j.chemphyslip.2019.104832

文献信息

• Design, Synthesis and In Vivo Evaluation of Sulfhydryl β-D-Glucose Cholesterols as Ligands for Brain Targeting Liposomes
  作者：Wei Fan、Chengyi Yan、Shan Qian、Nian Yao、Lei Tang、Yong Wu

  DOI：10.2174/157018010790945788

  日期：2010.5.1

  A novel sulfhydryl-β-D-glucose cholesterol 10a-10f as ligand for brain targeting liposomes was designed and synthesized. 10e was applied to the preparation of liposomal delivery system for achieving the brain-targeted delivery of the model drug tegafur in mice utilizing the glucose transporter member 1 (GLUT1). The results suggest the feasibility to enhance liposomes ability of delivering drug to brain by using the designed compound as liposome ligands.

  设计并合成了一种新型硫醇-β-D-葡萄糖胆固醇10a-10f作为脑靶向脂质体的配体。应用10e制备脂质体递送系统，旨在利用葡萄糖转运蛋白成员1（GLUT1）在 mice 中实现模型药物替加氟的脑靶向递送。结果表明，通过使用设计的化合物作为脂质体配体，可以增强脂质体向脑内递送药物的能力。
• 果糖和RGD肽共修饰的双重靶向三阴性乳腺癌的脂质材料
  申请人：四川大学

  公开号：CN110522923A

  公开（公告）日：2019-12-03

  本发明公开了一种新型脂质材料，用于实现三阴性乳腺癌靶向药物的传递。所述的新型脂质材料以赖氨酸为连接基团，分别与胆甾部分、果糖部分和RGD部分连接。可利用该新型脂质材料中的果糖和RGD分别与三阴性乳腺癌细胞表面高表达的果糖转运体GLUT5和整合素受体αvβ3之间的亲和力，实现对三阴性乳腺癌的双重靶向功能，发挥更强的三阴性乳腺癌靶向治疗作用。该新型脂质材料可用于脂质体、纳米粒、胶束等在内的不同剂型，所制成的载紫杉醇脂质体具有明显的三阴性乳腺癌靶向性，拥有广阔的应用前景。
• 葡萄糖和三苯基鏻修饰的脑肿瘤靶向脂质体的制备与应用
  申请人：四川大学

  公开号：CN113230417B

  公开（公告）日：2022-05-17

  本发明公开了葡萄糖和三苯基鏻共修饰的还原敏感型脑肿瘤靶向脂质体的制备与应用，用于实现脑肿瘤靶向药物的高效传递。所述的新型脂质体通过葡萄糖和三苯基鏻共同修饰，可分别识别血脑屏障和脑肿瘤细胞表面高表达的葡萄糖转运体GLUT1，以及与肿瘤细胞内线粒体发生静电作用，从细胞和细胞器两个层次，实现对血脑屏障、肿瘤组织以及线粒体的多重靶向功能，发挥更强的脑肿瘤靶向治疗作用。该新型脂质体可用于化疗药和作用于线粒体的化疗增敏剂的联合包载，用于协同治疗脑肿瘤，具有更精准的脑肿瘤靶向性，可提升化疗效果并减小毒副作用，拥有广阔的应用前景。
• Multiple targeted doxorubicin-lonidamine liposomes modified with p-hydroxybenzoic acid and triphenylphosphonium to synergistically treat glioma
  作者：Jiaqi Lu、Ru Li、Binsong Mu、Yao Peng、Yi Zhao、Yuesen Shi、Li Guo、Li Hai、Yong Wu

  DOI：10.1016/j.ejmech.2021.114093

  日期：2022.2

  A type of pH-sensitive multi-targeted brain tumor site-specific liposomes (Lip-CTPP) co-modified with p-hydroxybenzoic acid (p-HA) and triphenylphosphonium (TPP) were designed and prepared to co-load doxorubicin (DOX) and lonidamine (LND). Lip-CTPP are promising potential carriers to exert the anti-glioma effect of DOX and LND collaboratively given the following features: 1) Lip-CTPP have a good pharmacokinetic

  一种与p共修饰的pH敏感性多靶点脑肿瘤位点特异性脂质体（Lip-CTPP）对羟基苯甲酸 (p-HA) 和三苯基鏻 (TPP) 进行了设计和制备，以共同负载多柔比星 (DOX) 和氯尼达明 (LND)。Lip-CTPP 是有希望的潜在载体，可以协同发挥 DOX 和 LND 的抗胶质瘤作用，具有以下特点： 1） Lip-CTPP 具有良好的药代动力学行为；2）Lip-CTPP可以通过p-HA与多巴胺/σ受体的亲和力，穿过血脑屏障（BBB）识别肿瘤细胞；3) 一旦酸敏感的酰胺键在内切/溶酶体中裂解以暴露 TPP 和质子胺基团，Lip-CTPP 就会带上高正电荷；4）带正电的Lip-CTPP通过静电吸附从内/溶酶体中逸出并在线粒体中积累；5）释放DOX和LND，协同增加抗肿瘤功效。我们的体外体内实验结果证实，Lip-CTPP可显着提高对肿瘤细胞增殖、迁移和侵袭的抑制率，促进细胞凋亡和坏死，干扰线粒
• Design, synthesis and biological evaluation for docetaxel-loaded brain targeting liposome with “lock-in” function
  作者：Xiaocen Li、Boyi Qu、Xiuxiu Jin、Li Hai、Yong Wu

  DOI：10.3109/1061186x.2013.865032

  日期：2014.4

  Background: Glucose-modified liposome showed a good brain-targeting ability. However, bidirectional transport of glucose transporter-1 (GLUT₁) might reversely pump drugs out of the brain before releasing from the liposomes. Purpose: To overcome the bidirectional delivery of GLUT₁, the thiamine disulfide system (TDS), with ability of "lock-in", was introduced and a new ligand, L-TDS-G, was designed and synthesized. Methods: The liposome was prepared and characterized for particle size, zeta potential, surface morphological property, encapsulation efficiency and release profile. C6 glioma cells were used as an in vitro model to access the cellular uptake abilities and cytotoxicity of the liposomes. Competition assay was performed to validate the GLUT₁-mediated transport mechanism. Furthermore, the brain targeting abilities of the liposomes were evaluated through in vivo. Results: The preliminary evaluation in vivo demonstrated that L-TDS-G-coated liposome has an improved targeting ability and significantly increased the area under the concentration-time of docetaxel in brain as compared to naked docetaxel, non-coated and L-G coated liposomes. The relative uptake efficiency and concentration efficiency were enhanced by 3.82- and 4.99-fold compared to that of naked docetaxel, respectively. Conclusion: The results of this study indicated that L-TDS-G-coated liposome is a promising drug delivery system to enhance the brain concentrations of chemotherapeutic agents.