4β-(1-carbomethoxypentyl-4-methyl-1,2,3-triazolyl)-4’-demethylepipodophyllotoxin

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4β-(1-carbomethoxypentyl-4-methyl-1,2,3-triazolyl)-4’-demethylepipodophyllotoxin
• 英文别名: methyl 6-[4-[[(5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]oxymethyl]triazol-1-yl]hexanoate
• 化学式: C₃₁H₃₅N₃O₁₀
• 分子量: 609.633
• InChiKey: DRUSJMFFCAPGHU-WMVTVRAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  150
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  6-溴己酸甲酯 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 5.5h， 生成 4β-(1-carbomethoxypentyl-4-methyl-1,2,3-triazolyl)-4’-demethylepipodophyllotoxin
  参考文献：
  名称：

  Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules

  摘要：

  The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of a focused library of etoposide analogues, with the identification of two novel small molecules exhibiting TOP2B-dependent toxicity. Our findings pave the way toward studying isoform-specific cellular processes by means of small molecule intervention.

  DOI：

  10.1021/acs.jmedchem.5b00473

文献信息

• Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules
  作者：Angelica Mariani、Alexandra Bartoli、Mandeep Atwal、Ka C. Lee、Caroline A. Austin、Raphaël Rodriguez

  DOI：10.1021/acs.jmedchem.5b00473

  日期：2015.6.11

  The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of a focused library of etoposide analogues, with the identification of two novel small molecules exhibiting TOP2B-dependent toxicity. Our findings pave the way toward studying isoform-specific cellular processes by means of small molecule intervention.