N-(4-amino-2-(hexyloxy)phenyl)-N-methylmethanesulfonamide | 1202544-73-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-amino-2-(hexyloxy)phenyl)-N-methylmethanesulfonamide
• CAS: 1202544-73-7
• 化学式: C₁₄H₂₄N₂O₃S
• 分子量: 300.422
• InChiKey: BEFQUWZVDOZZQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  20.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 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：

  胡椒酸酰氯 、 N-(4-amino-2-(hexyloxy)phenyl)-N-methylmethanesulfonamide 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以76%的产率得到N-[3-(n-hexyloxy)-4(methyl(methylsulfonyl)amino)phenyl]-1,3-benzodioxole-5-carboxamide
  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：

  N-(2-hexyloxy-4-nitrophenyl)-methanesulfonamide 在 iron(III) chloride 、 水 、 sodium hydride 、 锌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-amino-2-(hexyloxy)phenyl)-N-methylmethanesulfonamide
  参考文献：
  名称：

  Synthesis and biological evaluation of selective tubulin inhibitors as anti-trypanosomal agents

  摘要：

  African trypanosomiasis is still a threat to human health due to the severe side-effects of current drugs. We identified selective tubulin inhibitors that showed the promise to the treatment of this disease, which was based on the tubulin protein structural difference between mammalian and trypanosome cells. Further lead optimization was performed in the current study to improve the efficiency of the drug candidates. We used Trypanosoma brucei brucei cells as the parasite model, and human normal kidney cells and mouse macrophage cells as the host model to evaluate the compounds. One new analog showed great potency with an IC50 of 70 nM to inhibit the growth of trypanosome cells and did not affect the viability of mammalian cells. Western blot analyses reveal that the compound decreased tubulin polymerization in T. brucei cells. A detailed structure activity relationship (SAR) was summarized that will be used to guide future lead optimization. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2017.04.009

文献信息

• Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cells
  作者：Bin Su、Shiuan Chen

  DOI：10.1016/j.bmcl.2009.09.109

  日期：2009.12

  A series of COX-2 selective inhibitor nimesulide derivatives were synthesized. Their anti-cell proliferation activities were evaluated with a long-term estrogen deprived MCF-7aro (LTEDaro) breast cancer cell line, which is the biological model of aromatase inhibitor resistance for hormone-dependent breast cancer. Compared to nimesulide which inhibited LTEDaro cell proliferation with an IC50 at 170.30 mu M, several new compounds showed IC50 close to 1.0 mu M. (C) 2009 Elsevier Ltd. All rights reserved.