4-(5-Hydroxy-4-oxo-4H-chromene-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester | 868836-98-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 4-(5-Hydroxy-4-oxo-4H-chromene-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 4-(5-hydroxy-4-oxochromene-2-carbonyl)piperazine-1-carboxylate
• CAS: 868836-98-0
• 化学式: C₁₉H₂₂N₂O₆
• 分子量: 374.393
• InChiKey: IXYMYGBJEMROPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  96.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(5-Hydroxy-4-oxo-4H-chromene-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以26%的产率得到5-Hydroxy-2-(piperazine-1-carbonyl)chromen-4-one
  参考文献：
  名称：

  Piperazinobenzopyranones and Phenalkylaminobenzopyranones:  Potent Inhibitors of Breast Cancer Resistance Protein (ABCG2)

  摘要：

  In continuing research that led us to identify chromanone derivatives (J. Med. Chem. 2003, 46, 2125) as P-glycoprotein inhibitors, we obtained analogues able to modulate multidrug resistance (MDR) mediated by the breast cancer resistance protein (BCRP). The linkage of 5-hydroxybenzopyran-4-one to piperazines or phenalkylainines affords highly potent inhibitors of BCRP. By using sensitive (HCT116) and resistant colon cancer cells expressing BCRP, we evaluated the effect of 14 benzopyranone (chromone) derivatives on the accumulation and the cytotoxic effect of the anticancer drug, mitoxantrone. At 10 mu M, three compounds increased both intracellular accumulation and cytotoxicity of mitoxantrone in HCT116/R cells with a comparable rate as fumitremorgin C and Gleevec used as reference inhibitors. The most potent molecules 5b and 5c are still active at 1 mu M, whereas FTC shows weak inhibition. These molecules do not induce cell death as shown by the cell cycle distribution study, which makes them potential candidates for in vivo studies.

  DOI：

  10.1021/jm050705h
• 作为产物：
  描述：

  5-羟基-4-氧代-4H-色烯-2-羧酸 、 N-Boc-哌嗪 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以19%的产率得到4-(5-Hydroxy-4-oxo-4H-chromene-2-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Piperazinobenzopyranones and Phenalkylaminobenzopyranones:  Potent Inhibitors of Breast Cancer Resistance Protein (ABCG2)

  摘要：

  In continuing research that led us to identify chromanone derivatives (J. Med. Chem. 2003, 46, 2125) as P-glycoprotein inhibitors, we obtained analogues able to modulate multidrug resistance (MDR) mediated by the breast cancer resistance protein (BCRP). The linkage of 5-hydroxybenzopyran-4-one to piperazines or phenalkylainines affords highly potent inhibitors of BCRP. By using sensitive (HCT116) and resistant colon cancer cells expressing BCRP, we evaluated the effect of 14 benzopyranone (chromone) derivatives on the accumulation and the cytotoxic effect of the anticancer drug, mitoxantrone. At 10 mu M, three compounds increased both intracellular accumulation and cytotoxicity of mitoxantrone in HCT116/R cells with a comparable rate as fumitremorgin C and Gleevec used as reference inhibitors. The most potent molecules 5b and 5c are still active at 1 mu M, whereas FTC shows weak inhibition. These molecules do not induce cell death as shown by the cell cycle distribution study, which makes them potential candidates for in vivo studies.

  DOI：

  10.1021/jm050705h

文献信息

• Piperazinobenzopyranones and Phenalkylaminobenzopyranones:  Potent Inhibitors of Breast Cancer Resistance Protein (ABCG2)
  作者：Ahcène Boumendjel、Edwige Nicolle、Thomas Moraux、Bastien Gerby、Madeleine Blanc、Xavier Ronot、Jean Boutonnat

  DOI：10.1021/jm050705h

  日期：2005.11.1

  In continuing research that led us to identify chromanone derivatives (J. Med. Chem. 2003, 46, 2125) as P-glycoprotein inhibitors, we obtained analogues able to modulate multidrug resistance (MDR) mediated by the breast cancer resistance protein (BCRP). The linkage of 5-hydroxybenzopyran-4-one to piperazines or phenalkylainines affords highly potent inhibitors of BCRP. By using sensitive (HCT116) and resistant colon cancer cells expressing BCRP, we evaluated the effect of 14 benzopyranone (chromone) derivatives on the accumulation and the cytotoxic effect of the anticancer drug, mitoxantrone. At 10 mu M, three compounds increased both intracellular accumulation and cytotoxicity of mitoxantrone in HCT116/R cells with a comparable rate as fumitremorgin C and Gleevec used as reference inhibitors. The most potent molecules 5b and 5c are still active at 1 mu M, whereas FTC shows weak inhibition. These molecules do not induce cell death as shown by the cell cycle distribution study, which makes them potential candidates for in vivo studies.