4TCNA | 1000006-68-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4TCNA
• 英文别名: 3-[(2,2-dimethylchroman-6-yl)carbonylamino]-7-hydroxy-8-methyl-2-oxo-2H-chromen-4-yle toluene-4-sulfonate；[3-[(2,2-dimethyl-3,4-dihydrochromene-6-carbonyl)amino]-7-hydroxy-8-methyl-2-oxochromen-4-yl] 4-methylbenzenesulfonate
• CAS: 1000006-68-7
• 化学式: C₂₉H₂₇NO₈S
• 分子量: 549.601
• InChiKey: CWUUFRRUDHQROT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4TCNA 在 溴 、 溶剂黄146 作用下， 反应 24.0h， 以37%的产率得到6-bromo-3-(2,2-dimethylchroman-6-carboxamido)-7-hydroxy-8-methyl-2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors

  摘要：

  A series of substituted coumarins1-10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI50 values at a micromolar level in a diverse set of human cancer cells (GI50 = 2-30 μM) and induced a high apoptosis level in MCF-7 breast cancer cell line. The molecular signature of hsp90 inhibition was assessed by depletion of the Erα hsp90 client protein.

  DOI：

  10.1016/j.ejmech.2014.06.067
• 作为产物：
  描述：

  sodium novobiocin 在 吡啶 作用下， 以 乙醇 为溶剂， 反应 3.5h， 生成 4TCNA
  参考文献：
  名称：

  Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors

  摘要：

  A series of substituted coumarins1-10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI50 values at a micromolar level in a diverse set of human cancer cells (GI50 = 2-30 μM) and induced a high apoptosis level in MCF-7 breast cancer cell line. The molecular signature of hsp90 inhibition was assessed by depletion of the Erα hsp90 client protein.

  DOI：

  10.1016/j.ejmech.2014.06.067

文献信息

• New Novobiocin Analogues as Antiproliferative Agents in Breast Cancer Cells and Potential Inhibitors of Heat Shock Protein 90
  作者：Gaëlle Le Bras、Christine Radanyi、Jean-François Peyrat、Jean-Daniel Brion、Mouâd Alami、Véronique Marsaud、Barbara Stella、Jack-Michel Renoir

  DOI：10.1021/jm0707774

  日期：2007.11.1

  positions of coumarin which appeared to be essential for degradation of hsp90 client proteins. Removal of the noviose moiety in novobiocin together with introduction of a tosyl substituent at C-4 or C-7 coumarins provides 6e and 6f as lead structures which compared favorably with novobiocin as demonstrated by enhanced rates of cell death. The processing and activation of caspases 7 and 8 and the subsequent

  选择性hsp90抑制剂可同时破坏和消耗参与细胞增殖和存活，血管生成和转移的关键信号蛋白。作为hsp90的新型抑制剂，缺少诺维糖部分的新霉素类似物已进行了研究。已经产生了一系列新的3-氨基香豆素类似物，并在细胞增殖中进行了筛选，并且通过在人乳腺癌细胞中消耗雌激素受体，HER2，Raf-1和cdk4来评估hsp90抑制的分子标记。这项结构-活性关系研究强调了香豆素的C-4和/或C-7位置的关键作用，这对hsp90客户蛋白的降解至关重要。除去新霉素中的新葡糖部分，并在C-4或C-7香豆素上引入甲苯磺酰基取代基，可提供6e和6f作为前导结构，与新霉素相比，有利于细胞死亡率的提高。半胱氨酸蛋白酶7和8的加工和激活以及随后的6e对PARP的切割表明刺激了外在凋亡途径。
• Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors
  作者：Davide Audisio、Délphine Methy-Gonnot、Christine Radanyi、Jack-Michel Renoir、Stéphanie Denis、Félix Sauvage、Juliette Vergnaud-Gauduchon、Jean-Daniel Brion、Samir Messaoudi、Mouad Alami

  DOI：10.1016/j.ejmech.2014.06.067

  日期：2014.8

  A series of substituted coumarins1-10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI50 values at a micromolar level in a diverse set of human cancer cells (GI50 = 2-30 μM) and induced a high apoptosis level in MCF-7 breast cancer cell line. The molecular signature of hsp90 inhibition was assessed by depletion of the Erα hsp90 client protein.