methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-(ethylcarbamoylamino)-7-fluoro-13-methoxycarbonyl-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 | 1416209-19-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-(ethylcarbamoylamino)-7-fluoro-13-methoxycarbonyl-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: 1416209-19-2
• 化学式: C₄₉H₆₃FN₆O₉
• 分子量: 899.072
• InChiKey: JKOCSXUHVWUWAV-MKUCKLRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  65
• 可旋转键数：
  12
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  175
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  10'-fluorocatharanthine 在 盐酸 、 sodium tetrahydroborate 、 cobalt(II) chloride hexahydrate 、 iron(III) chloride hexahydrate 作用下， 以 四氢呋喃 、 2,2,2-三氟乙醇 、 水 为溶剂， 反应 8.5h， 生成 methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-(ethylcarbamoylamino)-7-fluoro-13-methoxycarbonyl-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
  参考文献：
  名称：

  [EN] C20'-UREA DERIVATIVES OF VINCA ALKALOIDS
  [FR] DÉRIVÉS D'ALCALOÏDES DE LA PERVENCHE À URÉE EN C20

  摘要：

  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。

  公开号：

  WO2014088657A1

文献信息

• A Remarkable Series of Vinblastine Analogues Displaying Enhanced Activity and an Unprecedented Tubulin Binding Steric Tolerance: C20′ Urea Derivatives
  作者：Erick K. Leggans、Katharine K. Duncan、Timothy J. Barker、Kristin D. Schleicher、Dale L. Boger

  DOI：10.1021/jm3015684

  日期：2013.2.14

  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.