10'-fluoro-20'-azidoleurosidine | 1416209-21-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 10'-fluoro-20'-azidoleurosidine
• 英文别名: methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-4-[(13S,15R,17R)-17-azido-17-ethyl-7-fluoro-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5(10),6,8-tetraen-13-yl]-12-ethyl-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: 1416209-21-6
• 化学式: C₄₆H₅₆FN₇O₈
• 分子量: 853.991
• InChiKey: USYAOAODKAESIV-NTLGHQMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  62
• 可旋转键数：
  11
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  10'-fluorocatharanthine 、 文多灵 在 盐酸 、 iron(III) chloride hexahydrate 、 sodium tetrahydroborate 、 叠氮化铯 、 ferric(III)oxalate hexahydrate 作用下， 以 2,2,2-三氟乙醇 、 水 为溶剂， 反应 2.5h， 以7%的产率得到10'-fluoro-20'-azidovinblastine
  参考文献：
  名称：

  A Remarkable Series of Vinblastine Analogues Displaying Enhanced Activity and an Unprecedented Tubulin Binding Steric Tolerance: C20′ Urea Derivatives

  摘要：

  A systematic series of previously inaccessible key C20' urea and thiourea derivatives of vinblastine were prepared from 20'-amino-vinblastine that was made accessible through a unique Fe(III)/NaBH4-mediated alkene functionalization reaction of anhydrovinblastine. Their examination defined key structural features of the urea-based analogues that contribute to their properties and provided derivatives that match or exceed the potency of vinblastine by as much as 10-fold in cell-based functional assays, which is directly related to their relative tubulin binding affinity. In contrast to expectations based on apparent steric constraints of the tubulin binding site surrounding the vinblastine C20' center depicted in an X-ray cocrystal structure, remarkably large C20' urea derivatives are accommodated.

  DOI：

  10.1021/jm3015684

文献信息

• [EN] C20'-UREA DERIVATIVES OF VINCA ALKALOIDS<br/>[FR] DÉRIVÉS D'ALCALOÏDES DE LA PERVENCHE À URÉE EN C20
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2014088657A1

  公开（公告）日：2014-06-12

  A vinca alkaloid compound that is substituted at the 20'-position with a urea or thiourea group is disclosed. The urea's proximal nitrogen atom bonded to the 20'-position carbon atom is secondary, whereas the distal nitrogen atom can be unsubstituted only when the compound contains an optionally present 10'-fluoro substituent, and is otherwise preferably mono- or di-substituted. Methods of preparing the compounds are disclosed as are compositions for their use and methods of treatment using a compound.

  本发明涉及一种在20'-位置上用脲或硫脲基取代的长春花生物碱化合物。脲的近端氮原子与20'-位置碳原子结合是二级的，而远端氮原子只有在该化合物含有可选的10'-氟取代基时才可能未取代，否则最好是单取代或双取代。揭示了制备该化合物的方法，以及使用该化合物的组合物和治疗方法。