10'-methylvinblastine | 854757-39-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 10'-methylvinblastine
• 英文别名: methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-7-methyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5(10),6,8-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate
• CAS: 854757-39-4
• 化学式: C₄₇H₆₀N₄O₉
• 分子量: 825.015
• InChiKey: AZWFJGLXHKHBHG-HXCFSDMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  60
• 可旋转键数：
  10
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  10'-methylanhydrovinblastine 在 盐酸 、 sodium tetrahydroborate 、 ferric(III)oxalate hexahydrate 、 2,2,2-三氟乙醇 作用下， 以 水 为溶剂， 反应 0.5h， 以40%的产率得到10'-methylvinblastine
  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

文献信息

• ANTI-CANCER PHOSPHONATE ANALOGS
  申请人：Boojamra Constantine G.

  公开号：US20100022467A1

  公开（公告）日：2010-01-28

  The invention is related to phosphorus substituted anti-cancer compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及磷取代的抗癌化合物、含有这些化合物的组合物以及包括给予这些化合物的治疗方法，还涉及用于制备这些化合物的过程和中间体。
• [EN] 10'-FLUORINATED VINCA ALKALOIDS PROVIDE ENHANCED BIOLOGICAL ACTIVITY AGAINST MDR CANCER CELLS<br/>[FR] VINCA-ALCALOÏDES 10'-FLUORÉS DOTÉS D'UNE ACTIVITÉ BIOLOGIQUE AUGMENTÉE CONTRE LES CELLULES CANCÉREUSES MULTIRÉSISTANTES
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2011103007A3

  公开（公告）日：2012-01-05
• US7452901B2
  申请人：——

  公开号：US7452901B2

  公开（公告）日：2008-11-18
• US7645747B2
  申请人：——

  公开号：US7645747B2

  公开（公告）日：2010-01-12