(Z)-5-bromo-3-{2-[3-(4-chlorophenyl)-5-(4-dimethylaminophenyl)-4,5-dihydropyrazol-1-yl]-4-oxo-4H-thiazol-5-ylidene}-1,3-dihydroindol-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (Z)-5-bromo-3-{2-[3-(4-chlorophenyl)-5-(4-dimethylaminophenyl)-4,5-dihydropyrazol-1-yl]-4-oxo-4H-thiazol-5-ylidene}-1,3-dihydroindol-2-one
• 英文别名: (5Z)-5-(5-bromo-2-oxo-1H-indol-3-ylidene)-2-[5-(4-chlorophenyl)-3-[4-(dimethylamino)phenyl]-3,4-dihydropyrazol-2-yl]-1,3-thiazol-4-one
• 化学式: C₂₈H₂₁BrClN₅O₂S
• 分子量: 606.93
• InChiKey: BWTDHNPBRTZOAZ-IZHYLOQSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.31
• 重原子数：
  38.0
• 可旋转键数：
  3.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  77.37
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  3-(4-chlorophenyl)-5-(4-(dimethylamino)phenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide 、 5-溴靛红 、 氯乙酸 在 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 反应 5.0h， 以67%的产率得到(Z)-5-bromo-3-{2-[3-(4-chlorophenyl)-5-(4-dimethylaminophenyl)-4,5-dihydropyrazol-1-yl]-4-oxo-4H-thiazol-5-ylidene}-1,3-dihydroindol-2-one
  参考文献：
  名称：

  Bradykinin antagonists and thiazolidinone derivatives as new potential anti-cancer compounds

  摘要：

  Glioblastoma (GB), the most aggressive brain tumour, and mantle cell lymphoma (MCL), a rare but very aggressive type of lymphoma, are highly resistant to chemotherapy. GB and MCL chemotherapy gives very modest results, the vast majority of patients experience recurrent disease. To find out the new treatment modality for drug-resistant GB and MCL cells, combining of bradykinin (BK) antagonists with conventional temozolomide (TMZ) treatment, and screening of thiazolidinones derivatives were the main objectives of this work. As it was revealed here, BKM-570 was the lead compound among BK antagonists under investigation (IC50 was 3.3 mu M) in human GB cells. It strongly suppressed extracellular signal-regulated kinases 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation. BK antagonists did not decrease the viability of MCL cells, thus showing the cell-specific mode, while thiazolidinone derivatives, a novel group of promising anti-tumour compounds inhibited proliferation of MCL cells: IC50 of ID 4526 and ID 4527 compounds were 0.27 mu M and 0.16 mu M, correspondingly. However, single agents are often not effective in clinic due to activation of collateral pathways in tumour cells. We demonstrated a strong synergistic effect after combinatorial treatment by BKM-570 together with TMZ that drastically increased cytotoxic action of this drug in rat and human glioma cells. Small proportion of cells was still viable after such treatment that could be explained by presence of TMZ-resistant cells in the population.It is possible to expect that the combined therapy aimed simultaneously at different elements of tumourigenesis will be more effective with lower drug concentrations than the first-line drug temozolomide used alone in clinics. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.06.046

文献信息

• Bradykinin antagonists and thiazolidinone derivatives as new potential anti-cancer compounds
  作者：Stanislav Avdieiev、Lajos Gera、Dmytro Havrylyuk、Robert S. Hodges、Roman Lesyk、Vincent Ribrag、Yegor Vassetzky、Vadym Kavsan

  DOI：10.1016/j.bmc.2014.06.046

  日期：2014.8

  Glioblastoma (GB), the most aggressive brain tumour, and mantle cell lymphoma (MCL), a rare but very aggressive type of lymphoma, are highly resistant to chemotherapy. GB and MCL chemotherapy gives very modest results, the vast majority of patients experience recurrent disease. To find out the new treatment modality for drug-resistant GB and MCL cells, combining of bradykinin (BK) antagonists with conventional temozolomide (TMZ) treatment, and screening of thiazolidinones derivatives were the main objectives of this work. As it was revealed here, BKM-570 was the lead compound among BK antagonists under investigation (IC50 was 3.3 mu M) in human GB cells. It strongly suppressed extracellular signal-regulated kinases 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation. BK antagonists did not decrease the viability of MCL cells, thus showing the cell-specific mode, while thiazolidinone derivatives, a novel group of promising anti-tumour compounds inhibited proliferation of MCL cells: IC50 of ID 4526 and ID 4527 compounds were 0.27 mu M and 0.16 mu M, correspondingly. However, single agents are often not effective in clinic due to activation of collateral pathways in tumour cells. We demonstrated a strong synergistic effect after combinatorial treatment by BKM-570 together with TMZ that drastically increased cytotoxic action of this drug in rat and human glioma cells. Small proportion of cells was still viable after such treatment that could be explained by presence of TMZ-resistant cells in the population.It is possible to expect that the combined therapy aimed simultaneously at different elements of tumourigenesis will be more effective with lower drug concentrations than the first-line drug temozolomide used alone in clinics. (C) 2014 Elsevier Ltd. All rights reserved.