4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)thiazol-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)thiazol-2-amine
• 英文别名: 4-(4-Ethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,3-thiazol-2-amine；4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,3-thiazol-2-amine
• 化学式: C₂₀H₂₂N₂O₄S
• 分子量: 386.472
• InChiKey: CRPRTDCUQNTZEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  丙烯酰碘 、 4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)thiazol-2-amine 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以50.6%的产率得到N,N-diallyl-4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)thiazol-2-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of diarylthiazole derivatives as antimitotic and antivascular agents with potent antitumor activity

  摘要：

  By switching position of the N and S atom in the thiazole ring which were similar to the previously reported agent 5-(4-ethoxyphenyl)-4-(3',4',5'-trimethoxyphenyl)thiazol-2-amine, a series of 4,5-diarylthiazole derivatives were synthesized using Friedel-Crafts reaction based on chemical modification of Combrestatatin A-4 (CA-4). Their antiproliferative activities were evaluated and identified as new microtubule destabilizing agents. Structure-activity relationship study indicated that compound 8a with 3,4,5-trimethoxyphenyl group at the C-4 position and 4-ethoxyphenyl group at the C-5 position of 2-amino substituted thiazole was of the most potent inhibitory activity in this series. 8a was found to exhibit the IC50 values of 8.4-26.4 nM in five human cancer cell lines, with comparable inhibition effects to CA-4. Moreover, 8a showed potency as a tubulin polymerization inhibitor, with colchicine site binding ability and comparable extent of inhibition against the growth of P-glycoprotein over-expressing multidrug resistant cell lines. Mechanism studies revealed that 8a could block the progression of cell cycle in the G2/M phase and result in cellular apoptosis in cancer cells. As a new tubulin destabilizing agent, 8a was also found high antivascular activity as it concentration-dependently reduced the cell migration and disrupted capillary like tube formation of HUVEC cells. Furthermore, 8a significantly suppressed the tumor growth in HCT116 and SK-OV-3 xenograft models with tumor growth inhibitory rate of 55.12% and 72.7%, respectively. Our studies highlighted that 8a was a promising microtubule targeting antitumor agent. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.055
• 作为产物：
  描述：

  3,4,5-三甲氧基苯乙酸 在 aluminum (III) chloride 、 草酰氯 、 溴 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 3.67h， 生成 4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)thiazol-2-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of diarylthiazole derivatives as antimitotic and antivascular agents with potent antitumor activity

  摘要：

  By switching position of the N and S atom in the thiazole ring which were similar to the previously reported agent 5-(4-ethoxyphenyl)-4-(3',4',5'-trimethoxyphenyl)thiazol-2-amine, a series of 4,5-diarylthiazole derivatives were synthesized using Friedel-Crafts reaction based on chemical modification of Combrestatatin A-4 (CA-4). Their antiproliferative activities were evaluated and identified as new microtubule destabilizing agents. Structure-activity relationship study indicated that compound 8a with 3,4,5-trimethoxyphenyl group at the C-4 position and 4-ethoxyphenyl group at the C-5 position of 2-amino substituted thiazole was of the most potent inhibitory activity in this series. 8a was found to exhibit the IC50 values of 8.4-26.4 nM in five human cancer cell lines, with comparable inhibition effects to CA-4. Moreover, 8a showed potency as a tubulin polymerization inhibitor, with colchicine site binding ability and comparable extent of inhibition against the growth of P-glycoprotein over-expressing multidrug resistant cell lines. Mechanism studies revealed that 8a could block the progression of cell cycle in the G2/M phase and result in cellular apoptosis in cancer cells. As a new tubulin destabilizing agent, 8a was also found high antivascular activity as it concentration-dependently reduced the cell migration and disrupted capillary like tube formation of HUVEC cells. Furthermore, 8a significantly suppressed the tumor growth in HCT116 and SK-OV-3 xenograft models with tumor growth inhibitory rate of 55.12% and 72.7%, respectively. Our studies highlighted that 8a was a promising microtubule targeting antitumor agent. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.055