N-[4-amino-2-(2,5-dimethylbenzyloxy)phenyl]-N-methyltrifluoromethanesulfonamide | 1445997-12-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[4-amino-2-(2,5-dimethylbenzyloxy)phenyl]-N-methyltrifluoromethanesulfonamide
• CAS: 1445997-12-5
• 化学式: C₁₇H₁₉F₃N₂O₃S
• 分子量: 388.411
• InChiKey: DYJIKYUAQJDLFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-[4-amino-2-(2,5-dimethylbenzyloxy)phenyl]-N-methyltrifluoromethanesulfonamide 、 4-溴苯甲酰氯 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以81%的产率得到N-[3-(2,5-dimethylbenzyloxy)-4-(methyl(trifluoromethylsulfonyl)amino)phenyl]-4-bromobenzamide
  参考文献：
  名称：

  Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors

  摘要：

  Heat shock protein 27 (Hsp27) is a chaperone protein, and its expression is increased in response to various stress stimuli including anticancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anticancer drug development.

  DOI：

  10.1021/jm4004736
• 作为产物：
  描述：

  2-(2,5-dimethylbenzyloxy)-4-nitroaniline 在 iron(III) chloride 、 sodium hydride 、 锌 作用下， 以 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.33h， 生成 N-[4-amino-2-(2,5-dimethylbenzyloxy)phenyl]-N-methyltrifluoromethanesulfonamide
  参考文献：
  名称：

  Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors

  摘要：

  Heat shock protein 27 (Hsp27) is a chaperone protein, and its expression is increased in response to various stress stimuli including anticancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anticancer drug development.

  DOI：

  10.1021/jm4004736