| 960624-15-1

• 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
• CAS: 960624-15-1
• 化学式: C₃₉H₆₈O₆
• 分子量: 632.965
• InChiKey: KWQOSHDPIYESBT-RZZNUEQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  45.0
• 可旋转键数：
  17.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  63.22
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  在 N-甲基吗啉 、 对甲苯磺酸 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 5.33h， 生成
  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
• 作为产物：
  描述：

  胆甾-5-烯-3-醇 在 吡啶 、 四丁基硫酸氢铵 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 生成
  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.
• Dual-targeting liposome modified by glutamic hexapeptide and folic acid for bone metastatic breast cancer
  作者：Yang Yang、Ze Zhao、Changwei Xie、Yi Zhao

  DOI：10.1016/j.chemphyslip.2020.104882

  日期：2020.5

  Bone is the most common organ affected by metastatic breast cancer. 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, herein, a novel bone metastasis-targeted glutamic hexapeptide-folic acid (Glu(6)-FA) derivative was designed and synthesized as liposome ligand to deliver PTX to bone metastasis 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. What's more, the antitumor effects of PTX-Glu(6)-FA-Lip were confirmed by the detection of cell cycle, migration, and further measurement of microtubule stabilization. In addition, the PTX-Glu(6)-FA-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)-FA-modified liposome showed excellent targeting activity to metastatic bone cancer. These findings suggested that Glu(6)-FA-Lip was a promising bone metastasis-targeting carrier for the delivery of PTX. This study may therefore be conducive to the field of bone-targeting drugs delivery.