月桂56-3722 | 215604-75-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: 月桂56-3722
• 英文名称: 20(S)-20-O-{N^α-[4-(3-O-methyl-β-L-fucopyranosyloxy)phenylaminothiocarbonyl]histidylvalyl}camptothecin
• 英文别名: Afeletecan；[(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] (2S)-2-[[(2S)-2-[[4-[(2R,3S,4R,5R,6S)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxyphenyl]carbamothioylamino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoate
• CAS: 215604-75-4
• 化学式: C₄₅H₄₉N₇O₁₁S
• 分子量: 895.99
• InChiKey: SLOJCSGNHWIKIG-JNYZSSQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  64
• 可旋转键数：
  14
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  268
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  p-aminophenyl 3-O-methyl-β-L-fucopyranoside 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.17h， 生成 月桂56-3722
  参考文献：
  名称：

  Design and Optimization of 20-O-Linked Camptothecin Glycoconjugates as Anticancer Agents

  摘要：

  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.

  DOI：

  10.1021/jm010893l