10'-fluorovincristine | 1328885-66-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 10'-fluorovincristine
• 英文别名: 10'-fluoroanhydrovincristine；methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R)-17-ethyl-7-fluoro-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5(10),6,8,16-pentaen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate
• CAS: 1328885-66-0
• 化学式: C₄₆H₅₃FN₄O₉
• 分子量: 824.947
• InChiKey: PHPZGMXVAJZRTO-ZQDQSNJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  60
• 可旋转键数：
  10
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  151
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  10-fluorocatharanthine 在 盐酸 、 sodium tetrahydroborate 、 ferric(III)oxalate hexahydrate 、 2,2,2-三氟乙醇 、 iron(III) chloride hexahydrate 、 乙酸酐 作用下， 以 水 、 双氧水 为溶剂， 反应 5.0h， 生成 10'-fluorovincristine
  参考文献：
  名称：

  10′-Fluorovinblastine and 10′-Fluorovincristine: Synthesis of a Key Series of Modified Vinca Alkaloids

  摘要：

  A study on the impact of catharanthine C10 and C12 indole substituents on the biomimetic Fe(III)-mediated coupling with vindoline led to the discovery and characterization of two new and substantially more potent derivatives, 10'-fluorovinblastine and 10'-fluorovincristine. In addition to defining a pronounced and la unanticipated substituent effect on the biomimetic coupling, fluorine substitution at C10', which minimally alters the natural products, was found to uniquely enhance the activity 8-fold against both sensitive (IC50 = 800 pM, HCT116) and vinblastine-resistant tumor cell lines (IC50 = 80 nM, HCT166/VM46). As depicted in the X-ray structure of vinblastine bound to tubulin, this site resides at one end of the upper portion of the T-shaped conformation of the tubulin-bound molecule, suggesting that the 10'-fluorine substituent makes critical contacts with the protein at a hydrophobic site uniquely sensitive to steric interactions.

  DOI：

  10.1021/ml200236a