p-aminophenyl 3-O-methyl-β-L-fucopyranoside | 183878-21-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: p-aminophenyl 3-O-methyl-β-L-fucopyranoside
• 英文别名: p-Aminophenyl 3-o-methyl-beta-l-fucoside；(2R,3S,4R,5R,6S)-2-(4-aminophenoxy)-4-methoxy-6-methyloxane-3,5-diol
• CAS: 183878-21-9
• 化学式: C₁₃H₁₉NO₅
• 分子量: 269.298
• InChiKey: LDPYPPYGHWOOOX-RDVVHMHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  94.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  p-aminophenyl 3-O-methyl-β-L-fucopyranoside 生成 p-isothiocyanatophenyl 3-O-methyl-β-L-fucopyranoside
  参考文献：
  名称：

  20(S) camptothecin glycoconjugates

  摘要：

  本发明涉及20(S)-喜树碱的糖蛋白，其中3-O-甲基化的β-L-岩藻糖单元通过硫脲修饰的肽间隔连接到喜树碱衍生物的20-羟基基团。此外，本发明还涉及制备本发明化合物的方法以及它们作为药物的用途，特别是与肿瘤相关的用途。

  公开号：

  US06506734B1
• 作为产物：
  描述：

  p-nitrophenyl 3-O-methyl-β-L-fucoside 以88的产率得到p-aminophenyl 3-O-methyl-β-L-fucopyranoside
  参考文献：
  名称：

  20(S) camptothecin glycoconjugates

  摘要：

  本发明涉及20(S)-喜树碱的糖蛋白，其中3-O-甲基化的β-L-岩藻糖单元通过硫脲修饰的肽间隔连接到喜树碱衍生物的20-羟基基团。此外，本发明还涉及制备本发明化合物的方法以及它们作为药物的用途，特别是与肿瘤相关的用途。

  公开号：

  US06506734B1

文献信息

• Sugar-modified cytostatics
  申请人：Bayer Aktiengesellschaft

  公开号：US06271342B1

  公开（公告）日：2001-08-07

  The invention relates to cytostatics which, by modification with sugar, are tumor-specific. Suitable spacers ensure serum stability and at the same time an intracellular action.

  这项发明涉及通过与糖类改性的细胞毒药物，这些药物具有肿瘤特异性。合适的间隔物确保血清稳定性，同时也保证细胞内作用。
• Glycoconjugates from modified camptothecin derivatives (20-O-linkage)
  申请人：Bayer Aktiengesellschaft

  公开号：US06492335B1

  公开（公告）日：2002-12-10

  The present invention relates to glycoconjugates of camptothecin derivatives in which at least one carbohydrate component is linked via suitable spacers with the 20-hydroxyl group of a camptothecin derivative. The invention furthermore relates to processes for preparing the compounds according to the invention and to their use as medicaments, in particular in connection with cancer.

  本发明涉及康柏霉素衍生物的糖偶联物，其中至少一个糖组分通过适当的间隔物与康柏霉素衍生物的20-羟基基团连接。本发明还涉及制备本发明化合物的方法以及它们作为药物的用途，特别是与癌症有关。
• Lerchen, Hans-Georg; Von Dem Bruch, Karsten, Journal fur Praktische Chemie (Weinheim), 2000, vol. 342, # 8, p. 753 - 760
  作者：Lerchen, Hans-Georg、Von Dem Bruch, Karsten

  DOI：——

  日期：——
• Lectin-Mediated Drug Targeting: Discrimination of Carbohydrate-Mediated Cellular Uptake between Tumor and Liver Cells with Neoglycoconjugates Carrying Fucose Epitopes Regioselectively Modified in the 3-Position
  作者：Hans-Georg Lerchen、Joerg Baumgarten、Norbert Piel、Victoria Kolb-Bachofen

  DOI：10.1002/(sici)1521-3773(19991216)38:24<3680::aid-anie3680>3.0.co;2-9

  日期：1999.12.16

  The circumvention of efficient "carbohydrate traps" in the liver is required for targeting glycoconjugates on tumor cells. As shown in the model system of bovine serum albumin (BSA) conjugates, the nature of R(1)-R(3) of the fucose epitope plays an important role in the discrimination of cellular uptake between tumor and liver cells as well as in the cytotoxic activity.
• Design and Optimization of 20-O-Linked Camptothecin Glycoconjugates as Anticancer Agents
  作者：Hans-Georg Lerchen、Joerg Baumgarten、Karsten von dem Bruch、Thomas E. Lehmann、Michael Sperzel、Grazyna Kempka、Heinz-Herbert Fiebig

  DOI：10.1021/jm010893l

  日期：2001.11.1

  To improve the biological profile of 20(S)-camptothecin, a novel class of 20-O-linked camptothecin glycoconjugates has been designed for preferential cellular uptake into tumor cells by an active transport mechanism. Such conjugates have been optimized for enhanced solubility, stabilization of the camptothecin lactone ring, sufficient hydrolytic and proteolytic stability, and for an overall improvement in tumor selectivity. The constitution of the peptide spacer has a major impact on stability and biological activity of the conjugates both in vitro and in vivo, Glycoconjugates 17-22 with valine residues at the linkage position to camptothecin are sufficiently stable and show good antitumor activity in vitro against HT29 and other tumor cell lines. Fluorescence microscopy and flow cytometry experiments indicate that glycoconjugates such as 19 are taken up into lysosomal compartments of the tumor cell line HT29 by an active transport mechanism. The steric configuration of the particular amino acid residues linked to the camptothecin moiety has a major impact on the in vivo activity of the corresponding glycoconjugates in the breast cancer xenograft MX-1 model. Inhibiting tumor growth by > 96%, the glycoconjugates 19 and 21 show the best activity in this particular model and have been investigated more extensively. The glycoconjugate 19 compares favorably to topotecan 4 and glycoconjugate 21 with respect to toxicity against hematopoietic stem cells and hepatocytes. Based on its profile, 19 has been selected for clinical trials.