(2-((3,4-dimethoxyphenyl)amino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-((3,4-dimethoxyphenyl)amino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: [2-(3,4-Dimethoxyanilino)thieno[3,2-d]pyrimidin-4-yl]-(3,4,5-trimethoxyphenyl)methanone；[2-(3,4-dimethoxyanilino)thieno[3,2-d]pyrimidin-4-yl]-(3,4,5-trimethoxyphenyl)methanone
• 化学式: C₂₄H₂₃N₃O₆S
• 分子量: 481.529
• InChiKey: YILRDPFRRRRVOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,4-二氯噻吩并[3,2-D]嘧啶 在 sodium hydride 、 1,3-二甲基咪唑 碘 、 三氟乙酸 作用下， 以 2,2,2-三氟乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.5h， 生成 (2-((3,4-dimethoxyphenyl)amino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Design and synthesis of (2-(phenylamino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone analogues as potent anti-tubulin polymerization agents

  摘要：

  Anti-tubulin polymerization agents can disrupt tumor-vascular to exhibit anti-cancer potency. In this study, a series of substituted (2-(phenylamino)thieno(3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl) methanone analogues were designed and synthesized as anti-tubulin polymerization agents that interact with colchicine binding site. The anti-proliferative assay indicated that most of the target compounds displayed moderate to high potencies towards five tumor cell lines. The structure-activity relationship of these analogues was summarized. The most potent compound 14 was selected to assay its inhibition on the tubulin polymerization. 14 displayed potent inhibition against tubulin polymerization with an IC50 value of 4.1 +/- 0.1 mu M. The colchicine competition assay demonstrated that 14 inhibited tubulin polymerization by binding to the colchicine-binding site of tubulin. The molecular modeling study elucidated the binding mode of 14 in the colchicine binding site. The result of confocal immunofluorescent study proved that 14 can quickly disrupt the microtubules of Hela cells in a concentration dependent manner. Some experiments at cellular level were conducted to investigate the effects of 14 on cellular morphology, cell colony formation, cell cycle distribution, cell apoptosis and mitochondrial changes. The results demonstrated that 14 is a potent anti-tubulin agent with strong concentration dependent effect of inhibition of colony formation, induction of G2/M arrest and induction of apoptosis through mitochondrial pathway. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111679

文献信息

• Design and synthesis of (2-(phenylamino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone analogues as potent anti-tubulin polymerization agents
  作者：Chao Tian、Xuanzhen Chen、Zhili Zhang、Xiaowei Wang、Junyi Liu

  DOI：10.1016/j.ejmech.2019.111679

  日期：2019.12

  Anti-tubulin polymerization agents can disrupt tumor-vascular to exhibit anti-cancer potency. In this study, a series of substituted (2-(phenylamino)thieno(3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl) methanone analogues were designed and synthesized as anti-tubulin polymerization agents that interact with colchicine binding site. The anti-proliferative assay indicated that most of the target compounds displayed moderate to high potencies towards five tumor cell lines. The structure-activity relationship of these analogues was summarized. The most potent compound 14 was selected to assay its inhibition on the tubulin polymerization. 14 displayed potent inhibition against tubulin polymerization with an IC50 value of 4.1 +/- 0.1 mu M. The colchicine competition assay demonstrated that 14 inhibited tubulin polymerization by binding to the colchicine-binding site of tubulin. The molecular modeling study elucidated the binding mode of 14 in the colchicine binding site. The result of confocal immunofluorescent study proved that 14 can quickly disrupt the microtubules of Hela cells in a concentration dependent manner. Some experiments at cellular level were conducted to investigate the effects of 14 on cellular morphology, cell colony formation, cell cycle distribution, cell apoptosis and mitochondrial changes. The results demonstrated that 14 is a potent anti-tubulin agent with strong concentration dependent effect of inhibition of colony formation, induction of G2/M arrest and induction of apoptosis through mitochondrial pathway. (C) 2019 Elsevier Masson SAS. All rights reserved.