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 | 960624-20-8

• 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: 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
• CAS: 960624-20-8
• 化学式: C₃₅H₆₀O₆
• 分子量: 576.858
• InChiKey: JKNMROJLWJKFJH-AZNRHKSASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.55
• 重原子数：
  41.0
• 可旋转键数：
  17.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  74.22
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  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 在 N-甲基吗啉氧化物 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  抗坏血酸修饰的脑特异性脂质体给药系统具有“锁定”功能。

  摘要：

  在这项研究中，设计并合成了具有“锁定”功能的新型脑靶向抗坏血酸（AA）衍生物作为脂质体配体，以制备新型脂质体，以实现药物制剂通过葡萄糖转运蛋白1（GLUT 1）的有效递送。）和依赖Na +的维生素C转运蛋白（SVCT 2）。制备脂质体并根据粒径，ζ电势，包封效率，释放曲线，稳定性，溶血性和细胞毒性来表征。体内初步评估证明了与裸紫杉萜，未包被的和AA包被的脂质体相比，AA-硫胺素二硫化物系统（TDS）包被的脂质体具有改善的靶向能力，并显着增加了多西他赛（DTX）的脑部浓度。与裸紫杉萜相比，相对吸收效率和浓缩效率分别提高了3.24倍和5.62倍。分布数据和药代动力学参数均表明抗坏血酸硫胺素二硫化物输送系统是增强中枢神经系统（CNS）药物向大脑输送能力的有前途的载体。

  DOI：

  10.1016/j.chemphyslip.2019.01.005
• 作为产物：
  描述：

  胆甾-5-烯-3-醇 在 吡啶 、 四丁基硫酸氢铵 、 对甲苯磺酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 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：

  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

• 一种双重脑肿瘤靶向脂质材料及其应用
  申请人：四川大学

  公开号：CN108743953B

  公开（公告）日：2021-06-01

  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。
• 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.
• Design, synthesis and preliminary bio-evaluation of glucose–cholesterol derivatives as ligands for brain targeting liposomes
  作者：Fan Lei、Wei Fan、Xian Kun Li、Shan Wang、Li Hai、Yong Wu

  DOI：10.1016/j.cclet.2010.12.056

  日期：2011.7

  A series of glucose cholesterol derivatives 8a-8e as ligands for brain targeting liposomes were synthesized. The preparation of compound 6 involved temporary protection of glucose with chlorotrimethylsilicane and hexamethyldisilazane followed by selectively hydrolyzed. The known cholesteryl tosylate 1 were coupled to ethylene glycols to afford alcohol 2a-2e. Substitution and deprotection of alcohol 2a-2e furnished the acids 4a-4e, which was condensed with compound 6 to get compounds 7a-7e, and then was deprotected in tetrahydrofuran with TFA to obtain the title compounds. As a model drug, tegafur was entrapped by liposomes coupled with 8b, and preliminary in vivo evaluation shown 8b could enhance the ability of liposomes delivering tegafur across the blood brain barrier. (C) 2011 Yong Wu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
• Dual-active targeting liposomes drug delivery system for bone metastatic breast cancer: Synthesis and biological evaluation
  作者：Ze Zhao、Yi Zhao、Changwei Xie、Changqing Chen、Dong Lin、Sheng Wang、Dong Lin、Xinhua Cui、Zhongshuai Guo、Junfeng Zhou

  DOI：10.1016/j.chemphyslip.2019.104785

  日期：2019.9

  Bone is the most common organ affected by metastatic breast cancer. Targeting cancers within the bone remains a great challenge due to the inefficient delivery of therapeutic to bone. In order to increase the distribution of paclitaxel (PTX) in bone metastases, in this study, a novel bone-targeted glutamic oligopeptides-RGD peptide (Glu(6)-RGD) derivative was designed and synthesized as liposome ligand for preparing liposome to effectively deliver PTX to bone metastases. The liposome was prepared and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cytotoxicity were also characterized. What's more, the Glu(6)-RGD-Lip showed superior targeting ability in vitro and in vivo evaluation as compared to naked PTX, non-coated, singly-modified and co-modified by physical blending liposomes. All the results suggested that Glu(6)-RGD-modified liposome showed excellent targeting activity to metastatic bone cancer. This study may be conducive to the field of bone-targeting drugs delivery.
• Design, synthesis and biological evaluation of multivalent glucosides with high affinity as ligands for brain targeting liposomes
  作者：Boyi Qu、Xiaocen Li、Mei Guan、Xun Li、Li Hai、Yong Wu

  DOI：10.1016/j.ejmech.2013.10.007

  日期：2014.1

  The new bifunctional cluster glucosides were designed and synthesized as liposome ligands for preparing novel liposome to achieve the effective delivery of drug formulations to brain by GLUT1. Docetaxel-loaded five liposomes were prepared successfully and tested in the animals. Results from the in vivo distribution study after i.v. administration of these five liposomes and blank-docetaxel indicated that the coupled liposomes Lip-1, Lip-2, Lip-3, Lip-5 exhibited excellent transport ability across the BBB. In particular, they significantly increased the level of docetaxel in brain compared to blank-docetaxel and Lip. Among them, Lip-5 showed higher brain concentration. Both pharmacokinetics and distribution study in mice confirmed that this novel brain targeting drug delivery system was a promising carrier to enhance brain delivery capacity for CNS drugs. (C) 2013 Elsevier Masson SAS. All rights reserved.