methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-4-[(13S,15R,17S)-17-(cyclohexylcarbamoylamino)-17-ethyl-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-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 | 1416208-92-8

• 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-4-[(13S,15R,17S)-17-(cyclohexylcarbamoylamino)-17-ethyl-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-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: 1416208-92-8
• 化学式: C₅₃H₇₀N₆O₉
• 分子量: 935.174
• InChiKey: KDXWFXDCYKKYIE-UIJHABILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  68
• 可旋转键数：
  12
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  175
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  20'-aminovinblastine 、 环己基异氰酸酯 以 四氢呋喃 为溶剂， 反应 2.0h， 以51%的产率得到methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-4-[(13S,15R,17S)-17-(cyclohexylcarbamoylamino)-17-ethyl-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-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
  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